KR20190102978A - Composition for diagnosing cancer - Google Patents

Abstract

The present invention relates to a composition for diagnosing cancer, comprising an agent for measuring the expression level of cell migration inducing hyaluronidase 1 (CEMIP) protein or mRNA of a gene encoding the protein; and an agent for measuring the expression level of a carbohydrate antigen 19-9 (CA 19-9) protein or mRNA of the gene encoding the protein. The present invention also relates to a diagnostic kit comprising the composition, and a method of providing information for diagnosis of cancer using the composition.

Description

Composition for diagnosing cancer {Composition for diagnosing cancer}

The present invention relates to a composition capable of diagnosing cancer, a diagnostic kit comprising the same, and a method of providing information for diagnosing cancer using the composition.

Among the major diseases of modern people, researches on the treatment method and diagnosis method of cancer are relatively active mainly in lung cancer, liver cancer, gastric cancer, and the like that have high incidence. However, studies on esophageal cancer, colorectal cancer, and pancreatic cancer with low incidence are relatively poor.

In particular, pancreatic cancer initially does not feel much, and there are usually symptoms such as pain and weight loss after systemic metastasis has occurred, and thus the rate of healing is low, so regular diagnosis is very important. Most clinical symptoms are slow onset, prone to weakness, loss of appetite and weight loss. Pancreatic cancer is a fatal cancer with a 5-year survival rate of 1 to 4% and a median survival of 5 months. It has the poorest prognosis among human cancers. In addition, since 80% to 90% of patients are found in a state where curative resection is not possible, which is expected to be cured, the prognosis is poor and treatment mainly relies on chemotherapy. have.

The effectiveness of several anticancer drugs, including 5-fluorouracil, gemcitabine, and tarceva, which are known to be effective against pancreatic cancer to date, are extremely low. Only 15% or so suggests that the development of more effective early diagnosis and treatment is urgently needed to improve the prognosis of pancreatic cancer patients. Proper diagnosis and treatment of pancreatic cancer, a stage prior to the development of fatal pancreatic cancer, is critical for improving pancreatic cancer treatment outcomes.

Diagnosis of pancreatic cancer or pancreatic cancer precursor lesions has been performed with blood tests, X-ray angiography of the stomach and duodenum, biliary tract imaging through the skin and liver, and retrograde endoscopic cholangiography. Although disease lesions have been detected by these methods, ultrasonography and computed tomography are most commonly used in recent years. More accurate biopsies may be performed to obtain relatively accurate results. However, the diagnosis method is very inconvenient to perform the method, such as inaccuracy or pain to the patient, the subjects are reluctant to do so. Therefore, there has been a demand for the development of a test method capable of diagnosing pancreatic cancer or pancreatic cancer precursor lesion simply and quickly.

Recently, many imaging tests such as abdominal ultrasound (US), abdominal computed tomography (CT), magnetic resonance imaging (MRI) have been used to diagnose health checkups and other diseases of the pancreas. In practice, malignant lesions of the pancreas are frequently found. The lesions showing cystic lesions in the imaging are clinically important because the pathologic findings include a variety of diseases ranging from benign to premalignant and malignant lesions.

However, despite the development of imaging tests such as CT and MRI, it is still difficult to accurately differentiate the cystic lesions of the pancreas with various pathologic findings from benign lesions to precancerous and cystic lesions. Therefore, it is important to clinically discriminate whether the cystic lesions of the pancreas are malignant tumor lesions and, if so, whether they are still in the precancerous stage or already have malignant lesions.

Korean Patent Application Publication No. 2012-0009781 discloses an analysis method for measuring the expression level of XIST RNA in cancer tissue isolated from an individual in order to provide information necessary for diagnosing the pancreatic cancer of the individual. However, since the effects are insignificant in the diagnosis efficiency and accuracy, there is a need to find a marker that is more effective and to develop a diagnostic method using the same.

One object of the present invention is to provide a composition that can accurately and easily diagnose pancreatic cancer, especially among cancers.

Another object of the present invention is to provide a kit that can accurately and easily diagnose pancreatic cancer, especially among cancers.

Another object of the present invention is to provide a method for providing information for diagnosing pancreatic cancer, particularly among cancers.

Another object of the present invention is to provide a method for screening a drug for treating pancreatic cancer, among cancers in particular.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.

According to an embodiment of the present invention, an agent for measuring the expression level of mRNA of a Cell Migration Inducing Hyaluronidase 1 (CEMIP) protein or a gene encoding the protein; And

It relates to a diagnostic composition for cancer comprising a; CA 19-9 (carbohydrate antigen 19-9) protein or agent for measuring the expression level of mRNA of the gene encoding the protein.

In the present invention, the "CEMIP (Cell Migration Inducing Hyaluronidase 1)" is a protein encoded by the CEMIP gene in humans and binds to hyaluronic acid to catalyze the depolymerization of hyaluronic acid independently of CD44 and hyaluronidase. do. This function has also been demonstrated in mice. The CEMIP protein in the present invention may be composed of the amino acid sequence of SEQ ID NO: 1, but is not limited thereto.

In the present invention, "CA 19-9 (carbohydrate antigen 19-9)" corresponds to an epitope of sialic Lewis Lewis A structure, and corresponds to a carbohydrate antigen of mucin such as MUC1. In the present invention, the sequence of CA 19-9 may be defined as Siaα2,3Galβ1,3 (Fucα1,4) GlcNAc. Here, Sia is sialic acid, Gal is galactose, Fuc is fucose, and GlcNAc is N-acetylglucosamine.

In the present invention, as a disease to be diagnosed, the "cancer" indicates or indicates a physiological state characterized by cell growth that is not typically regulated in mammals. Cancers to be diagnosed in the present invention are pancreatic cancer, ovarian cancer, colon cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, thyroid cancer, parathyroid cancer, lung cancer, non-small cell lung cancer, prostate cancer, gallbladder cancer, biliary tract cancer, non-Hodgkin's lymphoma , Hodgkin's lymphoma, hematologic cancer, bladder cancer, kidney cancer, melanoma, colon cancer, bone cancer, skin cancer, head cancer, uterine cancer, rectal cancer, brain tumor, anal muscle cancer, fallopian tube carcinoma, endometrial carcinoma, vaginal cancer, vulvar carcinoma, esophageal cancer, small intestine Cancer, endocrine gland cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS central nervous system tumor, primary CNS lymphoma, spinal cord tumor, brain stem glioma or pituitary gland Adenomas, but may preferably be pancreatic cancer.

In the present invention, the "pancreatic cancer" refers to a cancer originating in pancreatic cells. There are many types of pancreatic cancer. Pancreatic adenocarcinoma of the pancreatic ducts accounts for about 90% of the pancreatic cancers. In addition, cystic cancer (cystic adenocarcinoma), endocrine tumors and the like. About 5 to 10% of patients with pancreatic cancer have genetic predisposition, and the family history of pancreatic cancer is about 7.8% in patients with pancreatic cancer, compared with 0.6% of the incidence of pancreatic cancer in the general public. Pancreatic cancer has a very poor prognosis with a 5 year survival rate of less than 5%. The reason for this is that most cancers are detected after progression. Surgical resection is possible within 20% at the time of discovery, and even if completely resected by the naked eye, the survival rate is not improved due to micrometastasis, and the response to chemotherapy and radiation treatment is poor. Because it is low. Thus, the most important way to improve survival is to detect and operate early when there are no symptoms or nonspecific.

In the present invention, the "diagnosis" refers to determining the susceptibility of a subject to a particular disease or disorder, determining whether the subject currently has a particular disease or disorder, or having a particular disease or disorder. Determining a subject's prognosis (eg, identifying a metastatic or metastatic cancer state, determining the stage of the cancer, or determining the responsiveness of the cancer to treatment), or therametrics (eg, for treatment efficacy Monitoring the state of an object to provide information). For the purposes of the present invention, the diagnosis is to determine whether the cancer is developed or the likelihood (danger).

In the present invention, the agent for measuring the expression level of each protein of the CEMIP and CA 19-9 is not particularly limited, for example, antibodies, oligos that specifically bind to the respective proteins of the CEMIP and CA 19-9 It may include one or more selected from the group consisting of peptides, ligands, peptide nucleic acid (PNA) and aptamer (aptamer).

In the present invention, the "antibody" refers to a substance which specifically binds to an antigen to generate an antigen-antibody reaction. For the purposes of the present invention, an antibody means an antibody that specifically binds to a CEMIP protein or a CA 19-9 protein. Antibodies of the invention include all polyclonal antibodies, monoclonal antibodies and recombinant antibodies. Such antibodies can be readily prepared using techniques well known in the art. For example, polyclonal antibodies are produced by methods well known in the art, including the steps of injecting an antigen of the CEMIP protein or CA 19-9 protein into an animal and collecting blood from the animal to obtain a serum comprising the antibody. Can be. Such polyclonal antibodies can be prepared from any animal, such as goats, rabbits, sheep, monkeys, horses, pigs, cattle, dogs, and the like. In addition, monoclonal antibodies are well known in the art by hybridoma methods (see Kohler and Milstein (1976) European Journal of Immunology 6: 511-519), or phage antibody library techniques (Clackson et al, Nature, 352). : 624-628, 1991; Marks et al, J. Mol. Biol., 222: 58, 1-597, 1991). Antibodies prepared by the above method can be isolated and purified using methods such as gel electrophoresis, dialysis, salt precipitation, ion exchange chromatography, affinity chromatography, and the like. In addition, antibodies of the invention include functional fragments of antibody molecules, as well as complete forms with two full length light chains and two full length heavy chains. The functional fragment of an antibody molecule means the fragment which has at least antigen binding function, and includes Fab, F (ab '), F (ab') 2, Fv, etc.

In the present invention, "PNA (Peptide Nucleic Acid)" refers to a polymer artificially synthesized, similar to DNA or RNA, and was first introduced by Nielsen, Egholm, Berg and Buchardt in 1991 at the University of Copenhagen, Denmark. DNA has a phosphate-ribose sugar backbone, whereas PNA has a repeated N- (2-aminoethyl) -glycine backbone linked by peptide bonds, which greatly increases binding and stability to DNA or RNA, leading to molecular biology. It is used in diagnostic analysis and antisense therapies. PNAs are described in Nielsen PE, Egholm M, Berg RH, Buchardt O (December 1991). "Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide". Science 254 (5037): 1497-1500.

In the present invention, the "aptamer" is an oligonucleic acid or peptide molecule, and the general contents of the aptamer are described in Bock LC et al., Nature 355 (6360): 5646 (1992); Hoppe-Seyler F, Butz K "Peptide aptamers: powerful new tools for molecular medicine". J Mol Med. 78 (8): 42630 (2000); Cohen BA, Colas P, Brent R. "An artificial cell-cycle inhibitor isolated from a combinatorial library". Proc Natl Acad Sci USA. 95 (24): 142727 (1998).

In the present invention, the agent for measuring the expression level of the mRNA of the gene encoding the protein of each of the CEMIP and CA 19-9 primers that specifically bind to the mRNA of the gene encoding each of the CEMIP protein or CA 19-9 protein It may comprise one or more selected from the group consisting of a probe and an antisense nucleotide.

In the present invention, the "primer" is a fragment that recognizes a target gene sequence, but includes a pair of primers in the forward and reverse direction, but is preferably a primer pair providing an analysis result having specificity and sensitivity. High specificity can be imparted when the nucleic acid sequence of the primer is a sequence that is inconsistent with the non-target sequence present in the sample so that only the target gene sequence containing the complementary primer binding site is amplified and does not cause nonspecific amplification. .

In the present invention, the "probe" refers to a substance that can specifically bind to a target substance to be detected in a sample, and means a substance that can specifically confirm the presence of the target substance in the sample through the binding. The type of probe is a material commonly used in the art, but is not limited. Preferably, the probe may be a peptide nucleic acid (PNA), a locked nucleic acid (LNA), a peptide, a polypeptide, a protein, an RNA, or a DNA. It is PNA. More specifically, the probes are biomaterials, including those derived from or similar to organisms or produced in vitro, for example, enzymes, proteins, antibodies, microorganisms, animal and plant cells and organs, neurons, DNA, and It may be RNA, DNA includes cDNA, genomic DNA, oligonucleotides, RNA includes genomic RNA, mRNA, oligonucleotides, examples of proteins may include antibodies, antigens, enzymes, peptides and the like.

In the present invention, the term "Locked nucleic acids" refers to a nucleic acid analogue including a 2'-O and a 4'-C methylene bridge [J Weiler, J Hunziker and J Hall Gene Therapy (2006) 13, 496.502. ]. LNA nucleosides comprise the general nucleic acid bases of DNA and RNA and can form base pairs according to the Watson-Crick base pair rule. However, due to the 'locking' of molecules due to methylene bridges, LNAs do not form ideal shapes at Watson-Crick bonds. When LNAs are included in DNA or RNA oligonucleotides, LNAs can be paired with complementary nucleotide chains faster to increase the stability of the double helix. In the present invention, the "antisense" is a sequence of nucleotide bases in which an antisense oligomer hybridizes with a target sequence in RNA by Watson-Crick base pairing, thereby allowing the formation of mRNA and RNA: oligomeric heterodimers typically within the target sequence. And oligomers having a backbone between subunits. The oligomer may have exact sequence complementarity or approximate complementarity to the target sequence.

Since the information of the CEMIP or CA 19-9 protein according to the present invention, or mRNA of the gene encoding them is known, those skilled in the art based on this, primers, probes or antisense nucleotides that specifically bind to the mRNA of the gene encoding the protein It will be easy to design.

According to another embodiment of the invention, the present invention relates to a diagnostic kit for cancer comprising a diagnostic composition for cancer according to the present invention.

In the present invention, the diagnosis kit may be used to diagnose whether or not the cancer disease develops.

In the present invention, the cancer is a disease targeted for the diagnosis of pancreatic cancer, ovarian cancer, colon cancer, gastric cancer, liver cancer, breast cancer, cervical cancer, thyroid cancer, parathyroid cancer, lung cancer, non-small cell lung cancer, prostate cancer, gallbladder cancer, biliary cancer Non-Hodgkin's lymphoma, Hodgkin's lymphoma, hematologic cancer, bladder cancer, kidney cancer, melanoma, colon cancer, bone cancer, skin cancer, head cancer, uterine cancer, rectal cancer, brain tumor, anal muscle cancer, fallopian tube carcinoma, endometrial carcinoma, vaginal cancer, vulvar carcinoma, Esophageal cancer, small intestine cancer, endocrine adenocarcinoma, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS central nervous system tumor, primary CNS lymphoma, spinal cord tumor, brain stem nerve Glioma or pituitary adenoma, but preferably pancreatic cancer.

In the present invention, the kit may be an RT-PCR kit, a DNA chip kit, an ELISA kit, a protein chip kit, a rapid kit, or a multiple reaction monitoring (MRM) kit, but is not limited thereto.

The diagnostic kit for cancer of the present invention may further include one or more other component compositions, solutions or devices suitable for the analysis method.

For example, in the present invention, the diagnostic kit for cancer may further include essential elements necessary for performing reverse transcriptase. The reverse transcription polymerase kit includes primer pairs specific for the gene encoding the marker protein. The primer is a nucleotide having a sequence specific to the nucleic acid sequence of the gene, it may have a length of about 7 bp to 50 bp, more preferably about 10 bp to 30 bp. It may also include primers specific for the nucleic acid sequence of the control gene. Other reverse transcriptase kits include test tubes or other suitable containers, reaction buffers (pH and magnesium concentrations vary), deoxynucleotides (dNTPs), enzymes such as Taq-polymerase and reverse transcriptase, DNase, RNase inhibitor DEPC -May include DEPC-water, sterile water, and the like.

In addition, the diagnostic kit of the present invention may include the necessary elements necessary to perform the DNA chip. The DNA chip kit may include a substrate on which a cDNA or oligonucleotide corresponding to a gene or a fragment thereof is attached, and a reagent, a preparation, an enzyme, or the like for preparing a fluorescent label probe. The substrate may also comprise cDNA or oligonucleotide corresponding to the control gene or fragment thereof.

In addition, the diagnostic kit of the present invention may include necessary elements necessary to perform an ELISA. ELISA kits contain antibodies specific for the protein. Antibodies are antibodies that have high specificity and affinity for marker proteins and have little cross-reactivity to other proteins, such as monoclonal antibodies, polyclonal antibodies, or recombinant antibodies. The ELISA kit can also include antibodies specific for the control protein. Other ELISA kits can bind reagents that can detect bound antibodies, such as labeled secondary antibodies, chromophores, enzymes (eg conjugated with the antibody) and substrates or antibodies thereof. Other materials and the like.

According to another embodiment of the invention, measuring the expression level of the mRNA of the Cell Migration Inducing Hyaluronidase 1 (CEMIP) protein or the gene encoding the protein in a biological sample isolated from the subject; And

Measuring the expression level of a CA 19-9 protein or mRNA of a gene encoding the protein in a biological sample isolated from a subject of interest. It is about.

In the present invention, the "target individual" refers to an individual who is uncertain about whether the cancer develops and has a high possibility of developing the cancer.

As used herein, the term "biological sample" refers to any substance, biological fluid, tissue or cell obtained from or derived from an individual, for example whole blood, leukocytes, peripheral blood mononuclear. Cells (peripheral blood mononuclear cells), leukocyte buffer coat, plasma, serum, sputum, tears, mucus, nasal washes, nasal aspirate (nasal aspirate), breath, urine, semen, saliva, peritoneal washings, ascites, cystic fluid, meningeal fluid Amniotic fluid, glandular fluid, pancreatic fluid, lymphatic fluid, pleural fluid, nipple aspirate, bronchial aspirate, synovial fluids, joint aspirates, organ secretions, cells, cell extracts May include cerebrospinal fluid, but is preferably a liquid biopsy obtained for pathological histological examination by injecting a hollow needle into an organ in vivo without dissecting the skin of a patient with high incidence , Tissue, cells, blood, serum, plasma, saliva, sputum or ascites, etc. of the patient).

The present invention may include measuring the expression level of mRNA of the CEMIP protein or a gene encoding the same in the biological sample separated as described above.

In addition, the present invention may include measuring the expression level of the mRNA of the CA 19-9 protein or a gene encoding the same in the biological sample isolated as described above.

MRNA of the CEMIP protein or a gene encoding the same in the present invention; Or CA 19-9 protein or mRNA of the gene encoding the same; the order of measuring the expression level is not particularly limited, and the expression level of the mRNA of the CEMIP protein or the gene encoding the same first measured CA 19-9 protein Alternatively, the expression level of mRNA of the gene encoding the same may be measured, or the expression level of the mRNA of the CA 19-9 protein or the gene encoding the same is first measured, and then the expression level of the mRNA of the CEMIP protein or the gene encoding the same is determined. The expression level of mRNA of the CEMIP protein or the gene encoding the same and the mRNA level of the CA 19-9 protein or the gene encoding the same can be measured simultaneously.

In the present invention, the agent for measuring the expression level of the CEMIP protein or the CA 19-9 protein is not particularly limited, but preferably an antibody or oligopeptide that specifically binds to each of the proteins of the CEMIP and CA 19-9. It may include one or more selected from the group consisting of ligand, PNA (peptide nucleic acid) and aptamer (aptamer).

In the present invention, the expression level of the CEMIP protein or the CA 19-9 protein may be measured or compared with a protein chip analysis, immunoassay, ligand binding assay, or MALDI-TOF (Matrix Assisted Laser Desorption / Ionization Time of Flight Mass). Spectrometry (SEM) -Sulface Enhanced Laser Desorption / Ionization Time of Flight Mass Spectrometry (SELDI-TOF) analysis, radioimmunoassay, radioimmunoproliferation, oukteroni immunodiffusion, rocket immunoelectrophoresis, tissue immunostaining, complement fixation assay, 2D electrophoresis, liquid chromatography-mass spectrometry (LC-MS), liquid chromatography-mass spectrometry / mass spectrometry (LC-MS / MS), western blotting and enzyme linked immunosorbentassay (ELISA) Etc., but is not limited thereto.

In the present invention, the agent for measuring the expression level of the mRNA of the gene encoding the CEMIP protein or mRNA of the gene encoding the CA 19-9 protein is determined in the mRNA of the gene encoding the protein of each of the CEMIP and CA 19-9 It may comprise one or more selected from the group consisting of primers, probes and antisense nucleotides that specifically bind.

As an analytical method for measuring the amount of mRNA by the process of confirming the presence and expression of mRNA of the gene encoding the protein of each of the CEMIP and CA 19-9 in the present invention, reverse transcription polymerase reaction (RT-PCR), Competitive RT-PCR, Real-time RT-PCR, RNase protection assay (RPA), Northern blotting, and DNA chips. It is not limited to this.

The expression level of mRNA of a CEMIP protein or a gene encoding the same as measured for a biological sample of a subject of interest in the present invention; And the expression level of mRNA of the CA 19-9 protein or a gene encoding the same; If at least one of the increased compared to the normal control, it may include the step of predicting a high probability of the cancer.

In the present invention, the expression level of the CEMIP protein measured in the biological sample of the subject of interest is at least 0.2 ng / ml, at least 0.21 ng / ml, or at least 0.218 ng / ml; And the expression level of the CA 19-9 protein is at least 35 U / ml, at least 36 U / ml, or at least 37 U / ml; In the case of at least one, it may include the step of predicting the high probability of the cancer.

In the present invention, the cancer is pancreatic cancer, ovarian cancer, colon cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, thyroid cancer, parathyroid cancer, lung cancer, non-small cell lung cancer, prostate cancer, gallbladder cancer, biliary tract cancer, non-Hodgkin's lymphoma, Hodgkin's lymphoma , Hematological cancer, bladder cancer, kidney cancer, melanoma, colon cancer, bone cancer, skin cancer, head cancer, uterine cancer, rectal cancer, brain tumor, anal mammary cancer, fallopian tube carcinoma, endometrial carcinoma, vaginal cancer, vulvar carcinoma, esophageal cancer, small intestine cancer, endocrine cancer , Adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS central nervous system tumor, primary CNS lymphoma, spinal cord tumor, brain stem glioma or pituitary adenoma , Preferably pancreatic cancer.

According to another embodiment of the present invention, the prognosis of cancer comprising measuring the expression level of the Cell Migration Inducing Hyaluronidase (CEMIP) protein or mRNA of the gene encoding the protein in a biological sample isolated from the subject of interest. It relates to an information providing method for predicting the.

In the present invention, the "target individual" means an individual who has or is likely to develop the cancer.

As used herein, the term "biological sample" refers to any substance, biological fluid, tissue or cell obtained from or derived from an individual, for example whole blood, leukocytes, peripheral blood mononuclear. Cells (peripheral blood mononuclear cells), leukocyte buffer coat, plasma, serum, sputum, tears, mucus, nasal washes, nasal aspirate (nasal aspirate), breath, urine, semen, saliva, peritoneal washings, ascites, cystic fluid, meningeal fluid Amniotic fluid, glandular fluid, pancreatic fluid, lymphatic fluid, pleural fluid, nipple aspirate, bronchial aspirate, synovial fluids, joint aspirates, organ secretions, cells, cell extracts May include cerebrospinal fluid, but is preferably a liquid biopsy obtained for pathological histological examination by injecting a hollow needle into an organ in vivo without dissecting the skin of a patient with high incidence , Tissue, cells, blood, serum, plasma, saliva, sputum or ascites, etc. of the patient).

The present invention may include measuring the expression level of mRNA of the CEMIP protein or a gene encoding the same in the biological sample separated as described above.

The agent for measuring the expression level of the CEMIP protein in the present invention is not particularly limited, but preferably, an antibody, oligopeptide, ligand, peptide nucleic acid (PNA) and aptamer (aptamer) specifically binding to the protein of the CEMIP. It may include one or more selected from the group consisting of.

In the present invention, the expression level of the CEMIP protein is measured or compared with a method for analyzing protein chip, immunoassay, ligand binding assay, Matrix Assisted Laser Desorption / Ionization Time of Flight Mass Spectrometry (SELDI-TOF) analysis. (Sulface Enhanced Laser Desorption / Ionization Time of Flight Mass Spectrometry) analysis, radioimmunoassay, radioimmunoassay, oukteroni immunodiffusion, rocket immunoelectrophoresis, tissue immunostaining, complement fixation assay, two-dimensional electrophoresis analysis, liquid phase Liquid chromatography-mass spectrometry (LC-MS), liquid chromatography-mass spectrometry / mass spectrometry (LC-MS / MS), western blotting and enzyme linked immunosorbentassay (ELISA). It is not.

In the present invention, the agent for measuring the expression level of the mRNA of the gene encoding the CEMIP protein is at least one selected from the group consisting of primers, probes and antisense nucleotides specifically binding to the mRNA of the gene encoding the CEMIP protein. It may include.

As an analytical method for measuring the amount of mRNA in the process of confirming the presence and expression level of mRNA of the gene encoding the CEMIP protein in the present invention, reverse transcriptase (RT-PCR), competitive reverse transcriptase (Competitive) RT-PCR), real-time RT-PCR, RNase protection assay (RPA), Northern blotting, DNA chips, and the like, but are not limited thereto.

When the expression level of the CEMIP protein measured on the biological sample of the subject of interest is 0.4 ng / ml or more, 0.41 ng / ml or more, 0.42 ng / ml or more or 0.429 ng / ml or more, the prognosis is predicted to be poor. It may include a step.

When the expression level of the CEMIP protein measured on the biological sample of the subject of interest is 0.4 ng / ml or more, 0.41 ng / ml or more, 0.42 ng / ml or more, or 0.429 ng / ml or more, the survival period is 12 months or less. , 11 months or less, 10 months or less, or 9.8 months or less.

In the present invention, the cancer is pancreatic cancer, ovarian cancer, colon cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, thyroid cancer, parathyroid cancer, lung cancer, non-small cell lung cancer, prostate cancer, gallbladder cancer, biliary tract cancer, non-Hodgkin's lymphoma, Hodgkin's lymphoma , Hematological cancer, bladder cancer, kidney cancer, melanoma, colon cancer, bone cancer, skin cancer, head cancer, uterine cancer, rectal cancer, brain tumor, anal mammary cancer, fallopian tube carcinoma, endometrial carcinoma, vaginal cancer, vulvar carcinoma, esophageal cancer, small intestine cancer, endocrine cancer , Adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS central nervous system tumor, primary CNS lymphoma, spinal cord tumor, brain stem glioma or pituitary adenoma , Preferably pancreatic cancer.

In the present invention, by measuring the expression level of CEMIP and CA 19-9 markers from a biological sample of a desired individual, it is possible to accurately predict or diagnose the onset or possibility of developing cancer, particularly pancreatic cancer.

Figure 1 is a graph showing the results of comparing the expression level of the CEMIP protein in the serum of the pancreatic cancer patient and the normal control in one embodiment of the present invention.
Figure 2 shows the ROC curve of CEMIP, CA 19-9, or a combination of these proteins for diagnosing pancreatic cancer in one embodiment of the invention.
Figure 3 shows the distribution of expression levels of CEMIP and CA 19-9 protein in pancreatic cancer patients in one embodiment of the present invention.
Figure 4 shows the correlation between the survival of pancreatic cancer patients and the expression level of CEMIP protein in one embodiment of the present invention by Kaplan-Meier curve.

Hereinafter, the present invention will be described in detail by the following examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples.

Example

patient

Retrospective analyzes were performed on pancreatic cancer patients and normal control samples collected between 2007 and 2015. The normal control group was selected as an undiagnosed pancreatic cancer but classified into healthy individuals and benign tumor patients. Blood samples were taken for the following diagnosis. Basic information about the patient and clinical data on diagnosis, sex, location of cancer, levels of CA 19-9 in serum, chemotherapy and cancer staging were obtained from electronic medical records. Cancer stages were classified based on the 7th edition stage of the American Joint Committee on Cancer (AJCC).

Measurement of CA 19-9 and CEMIP Expression Levels

Expression levels of CA 19-9 were measured using a chemiluminescence immunoassay on the VITROS 3600 Immunodiagnostic System (Ortho-Clinical Diagnostics Inc., Raritan, NJ, USA). The diagnostic cut-off value of CA 19-9 corresponded to 37 U / ml. The expression level of CEMIP was measured using an enzyme-linked immunosorbent assay (ELISA). Blood samples were extracted from pancreatic cancer patients and normal controls without cancer to measure the expression level of CEMIP protein. 96-well CEMIP ELISA Kit (SER965Hu) is available from USCN Life Science, Inc. (Wuhan, China). The detection range of the ELISA kit used was 0.156-10 ng / ml. Standard curve concentrations of ELISA corresponded to 10, 5, 2.5, 1.25, 0.625, 0.312, and 0.156 ng / ml. The sensitivity of this assay or the lower limit of detection (LLD) was defined as the lowest protein concentration that can be distinguished from zero. This was determined by adding the two standard deviations to the mean absorbance values repeated 20 times and calculating the corresponding concentrations. No significant cross-reactivity or interference between CEMIP and analogs was observed.

Statistical analysis

All statistical analyzes were performed using SPSS version 20.0 for Windows (SPSS, Inc., Chicago, IL, USA), SAS (version 9.4, SAS Inc., Cary, NC, USA), and R package version 3.0.1. . A Student's t test was performed to compare serum values of normal controls and pancreatic cancer patients. The CEMIP cut-off value of the titrations associated with the diagnosis was calculated using the receiver operating characteristic curve (ROC curve) and the area under the ROC curve (AUROC). MedCalc version 11.1 was used for ROC analysis (MedCalc Sofware, Mariakerke, Belgium). The bootstrapping method (1,000 iterations) was applied for internal validation of AUROC. Contal and O'Quigley's methods were used to classify patients into high and low risk groups for overall survival, and CEMIP cut-off values were selected. Survival curves were analyzed using the Kaplan-Meier method, and differences between curves were analyzed using log-rank tests. P-values <0.05 were considered statistically significant. Univariate and multivariate analyzes were performed using Cox regression analysis to analyze risk factors affecting the survival of pancreatic cancer patients. The graph was drawn with GraphPad Prism 4 software (GraphPad Sofware, San Diego, CA, USA).

Patient characteristics

Serum samples were obtained from 324 patients and 49 normal controls diagnosed with pancreatic cancer from Severance Hospital. The normal control group consisted of 30 healthy individuals with bile duct stones (n = 2), gallbladder stones (n = 4), intrahepatic stones (n = 1), cholecystitis (n = 4), liver abscess (n = 1), and acute hepatitis (n = 1), acute pancreatitis (n = 1), duodenal polyp (n = 1), gastric ulcer (n = 1), and benign pancreatic cyst (n = 3). Table 1 below shows the characteristics of the patients. The median age of the patients was 63 years old (male, 64.5%), approximately 75% of patients were treated with conventional chemotherapy, and 170 patients (52%) were stage IV. He was diagnosed with pancreatic cancer. The median overall survival rate was 314 days (169 to 581 days). Median values of CA 19-9 and CEMIP expression levels in pancreatic cancer patients corresponded to 410.5 U / ml (40.8 to 3342.5) and 0.67 ng / ml (0.40 to 1.08), respectively.

Diagnosis of pancreatic cancer patient (1)

Using the Mann-Whitney U test, it was confirmed that the expression level of CA 19-9 was significantly increased in pancreatic cancer patients compared to the normal control group (medium value, pancreatic cancer patients: 410.5 U / ml, normal control group: 10.8 U / ml, P). <0.001). In addition, CEMIP also showed a significant increase in the expression level of pancreatic cancer patients compared to the normal control group (pancreatic cancer patients: 0.67 ng / ml, normal control group: 0.16 ng / ml, P <0.001) (Fig. 1). As a result of the ROC curve analysis, it was confirmed that the combination of the markers of CEMIP and CA 19-9 can be used as a diagnostic marker for pancreatic cancer (FIG. 2). In more detail, when pancreatic cancer was diagnosed using CA 19-9 or CEMIP alone, the sensitivity of both markers was only about 0.82, whereas when pancreatic cancer was diagnosed by the combination of CA 19-9 and CEMIP, the sensitivity was 0.92. It was confirmed that the remarkably improved (specificity (specificity) is 0.62) (Table 1).

division Sensitivity CEMIP only 0.82 CA 19-9 only 0.82 CEMIP + CA 19-9 0.92

Diagnosis of pancreatic cancer patient (2)

Of the 324 patients diagnosed with pancreatic cancer, 79 had a CA 19-9 expression level of less than 37 U / ml, and 19 patients had Lewis blood type A-B-. The expression level of CA 19-9 in patients with pancreatic cancer was relatively low at less than 37 U / ml, while the proportion of patients with relatively high CEMIP expression levels of 0.218 ng / ml or higher was 86.1%. That is, out of 79 patients with low CA 19-9 expression below 37 U / ml, 68 patients (86.1%) with CEMIP expression level above 0.218 ng / ml (86.1%) were diagnosed as pancreatic cancer patients. Could be (FIG. 3).

Prognostic Prediction in Patients with Pancreatic Cancer

Contal and O'Quigley methods were used to determine the CEMIP titration cut-off value to maximize the difference in survival (CEMIP = 0.429 ng / ml). Kaplan-Meier curves analyze the CEMIP expression level and the survival time of pancreatic cancer patients, and the mean survival time is 9.8 months for patients with CEMIP expression level of 0.429 ng / ml or more, while the CEMIP expression level is 0.429 ng / ml. The average survival time was less than 13.7 months, and the CEMIP expression level of 0.429 ng / ml or more was significantly shorter than the CEMIP expression level of 0.429 ng / ml. (log-rank test P = 0.0175) (FIG. 4).

Although the present invention has been described in detail above, the scope of the present invention is not limited thereto, and various modifications and changes can be made without departing from the technical spirit of the present invention described in the claims. It will be self-evident to those who have knowledge of.

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Gly Lys Gly Gly Ala Leu Glu Leu His Gly Gln Lys Lys Leu Ser 145 150 155 160 Trp Thr Phe Leu Asn Lys Thr Leu His Pro Gly Gly Met Ala Glu Gly                 165 170 175 Gly Tyr Phe Phe Glu Arg Ser Trp Gly His Arg Gly Val Ile Val His             180 185 190 Val Ile Asp Pro Lys Ser Gly Thr Val Ile His Ser Asp Arg Phe Asp         195 200 205 Thr Tyr Arg Ser Lys Lys Glu Ser Glu Arg Leu Val Gln Tyr Leu Asn     210 215 220 Ala Val Pro Asp Gly Arg Ile Leu Ser Val Ala Val Asn Asp Glu Gly 225 230 235 240 Ser Arg Asn Leu Asp Asp Met Ala Arg Lys Ala Met Thr Lys Leu Gly                 245 250 255 Ser Lys His Phe Leu His Leu Gly Phe Arg His Pro Trp Ser Phe Leu             260 265 270 Thr Val Lys Gly Asn Pro Ser Ser Ser Val Glu Asp His Ile Glu Tyr         275 280 285 His Gly His Arg Gly Ser Ala Ala Ala Arg Val Phe Lys Leu Phe Gln     290 295 300 Thr Glu His Gly Glu Tyr Phe Asn Val Ser Leu Ser Ser Glu Trp Val 305 310 315 320 Gln Asp Val Glu Trp Thr Glu Trp Phe Asp His Asp Lys Val Ser Gln                 325 330 335 Thr Lys Gly Gly Glu Lys Ile Ser Asp Leu Trp Lys Ala His Pro Gly             340 345 350 Lys Ile Cys Asn Arg Pro Ile Asp Ile Gln Ala Thr Thr Met Asp Gly         355 360 365 Val Asn Leu Ser Thr Glu Val Val Tyr Lys Lys Gly Gln Asp Tyr Arg     370 375 380 Phe Ala Cys Tyr Asp Arg Gly Arg Ala Cys Arg Ser Tyr Arg Val Arg 385 390 395 400 Phe Leu Cys Gly Lys Pro Val Arg Pro Lys Leu Thr Val Thr Ile Asp                 405 410 415 Thr Asn Val Asn Ser Thr Ile Leu Asn Leu Glu Asp Asn Val Gln Ser             420 425 430 Trp Lys Pro Gly Asp Thr Leu Val Ile Ala Ser Thr Asp Tyr Ser Met         435 440 445 Tyr Gln Ala Glu Glu Phe Gln Val Leu Pro Cys Arg Ser Cys Ala Pro     450 455 460 Asn Gln Val Lys Val Ala Gly Lys Pro Met Tyr Leu His Ile Gly Glu 465 470 475 480 Glu Ile Asp Gly Val Asp Met Arg Ala Glu Val Gly Leu Leu Ser Arg                 485 490 495 Asn Ile Ile Val Met Gly Glu Met Glu Asp Lys Cys Tyr Pro Tyr Arg             500 505 510 Asn His Ile Cys Asn Phe Phe Asp Phe Asp Thr Phe Gly Gly His Ile         515 520 525 Lys Phe Ala Leu Gly Phe Lys Ala Ala His Leu Glu Gly Thr Glu Leu     530 535 540 Lys His Met Gly Gln Gln Leu Val Gly Gln Tyr Pro Ile His Phe His 545 550 555 560 Leu Ala Gly Asp Val Asp Glu Arg Gly Gly Tyr Asp Pro Pro Thr Tyr                 565 570 575 Ile Arg Asp Leu Ser Ile His His Thr Phe Ser Arg Cys Val Thr Val             580 585 590 His Gly Ser Asn Gly Leu Leu Ile Lys Asp Val Val Gly Tyr Asn Ser         595 600 605 Leu Gly His Cys Phe Phe Thr Glu Asp Gly Pro Glu Glu Arg Asn Thr     610 615 620 Phe Asp His Cys Leu Gly Leu Leu Val Lys Ser Gly Thr Leu Leu Pro 625 630 635 640 Ser Asp Arg Asp Ser Lys Met Cys Lys Met Ile Thr Glu Asp Ser Tyr                 645 650 655 Pro Gly Tyr Ile Pro Lys Pro Arg Gln Asp Cys Asn Ala Val Ser Thr             660 665 670 Phe Trp Met Ala Asn Pro Asn Asn Asn Leu Ile Asn Cys Ala Ala Ala         675 680 685 Gly Ser Glu Glu Thr Gly Phe Trp Phe Ile Phe His His Val Pro Thr     690 695 700 Gly Pro Ser Val Gly Met Tyr Ser Pro Gly Tyr Ser Glu His Ile Pro 705 710 715 720 Leu Gly Lys Phe Tyr Asn Asn Arg Ala His Ser Asn Tyr Arg Ala Gly                 725 730 735 Met Ile Ile Asp Asn Gly Val Lys Thr Thr Glu Ala Ser Ala Lys Asp             740 745 750 Lys Arg Pro Phe Leu Ser Ile Ile Ser Ala Arg Tyr Ser Pro His Gln         755 760 765 Asp Ala Asp Pro Leu Lys Pro Arg Glu Pro Ala Ile Ile Arg His Phe     770 775 780 Ile Ala Tyr Lys Asn Gln Asp His Gly Ala Trp Leu Arg Gly Gly Asp 785 790 795 800 Val Trp Leu Asp Ser Cys Arg Phe Ala Asp Asn Gly Ile Gly Leu Thr                 805 810 815 Leu Ala Ser Gly Gly Thr Phe Pro Tyr Asp Asp Gly Ser Lys Gln Glu             820 825 830 Ile Lys Asn Ser Leu Phe Val Gly Glu Ser Gly Asn Val Gly Thr Glu         835 840 845 Met Met Asp Asn Arg Ile Trp Gly Pro Gly Gly Leu Asp His Ser Gly     850 855 860 Arg Thr Leu Pro Ile Gly Gln Asn Phe Pro Ile Arg Gly Ile Gln Leu 865 870 875 880 Tyr Asp Gly Pro Ile Asn Ile Gln Asn Cys Thr Phe Arg Lys Phe Val                 885 890 895 Ala Leu Glu Gly Arg His Thr Ser Ala Leu Ala Phe Arg Leu Asn Asn             900 905 910 Ala Trp Gln Ser Cys Pro His Asn Asn Val Thr Gly Ile Ala Phe Glu         915 920 925 Asp Val Pro Ile Thr Ser Arg Val Phe Phe Gly Glu Pro Gly Pro Trp     930 935 940 Phe Asn Gln Leu Asp Met Asp Gly Asp Lys Thr Ser Val Phe His Asp 945 950 955 960 Val Asp Gly Ser Val Ser Glu Tyr Pro Gly Ser Tyr Leu Thr Lys Asn                 965 970 975 Asp Asn Trp Leu Val Arg His Pro Asp Cys Ile Asn Val Pro Asp Trp             980 985 990 Arg Gly Ala Ile Cys Ser Gly Cys Tyr Ala Gln Met Tyr Ile Gln Ala         995 1000 1005 Tyr Lys Thr Ser Asn Leu Arg Met Lys Ile Ile Lys Asn Asp Phe Pro    1010 1015 1020 Ser His Pro Leu Tyr Leu Glu Gly Ala Leu Thr Arg Ser Thr His Tyr 1025 1030 1035 1040 Gln Gln Tyr Gln Pro Val Val Thr Leu Gln Lys Gly Tyr Thr Ile His                1045 1050 1055 Trp Asp Gln Thr Ala Pro Ala Glu Leu Ala Ile Trp Leu Ile Asn Phe            1060 1065 1070 Asn Lys Gly Asp Trp Ile Arg Val Gly Leu Cys Tyr Pro Arg Gly Thr        1075 1080 1085 Thr Phe Ser Ile Leu Ser Asp Val His Asn Arg Leu Leu Lys Gln Thr    1090 1095 1100 Ser Lys Thr Gly Val Phe Val Arg Thr Leu Gln Met Asp Lys Val Glu 1105 1110 1115 1120 Gln Ser Tyr Pro Gly Arg Ser His Tyr Tyr Trp Asp Glu Asp Ser Gly                1125 1130 1135 Leu Leu Phe Leu Lys Leu Lys Ala Gln Asn Glu Arg Glu Lys Phe Ala            1140 1145 1150 Phe Cys Ser Met Lys Gly Cys Glu Arg Ile Lys Ile Lys Ala Leu Ile        1155 1160 1165 Pro Lys Asn Ala Gly Val Ser Asp Cys Thr Ala Thr Ala Tyr Pro Lys    1170 1175 1180 Phe Thr Glu Arg Ala Val Val Asp Val Pro Met Pro Lys Lys Leu Phe 1185 1190 1195 1200 Gly Ser Gln Leu Lys Thr Lys Asp His Phe Leu Glu Val Lys Met Glu                1205 1210 1215 Ser Ser Lys Gln His Phe Phe His Leu Trp Asn Asp Phe Ala Tyr Ile            1220 1225 1230 Glu Val Asp Gly Lys Lys Tyr Pro Ser Ser Glu Asp Gly Ile Gln Val        1235 1240 1245 Val Val Ile Asp Gly Asn Gln Gly Arg Val Val Ser His Thr Ser Phe    1250 1255 1260 Arg Asn Ser Ile Leu Gln Gly Ile Pro Trp Gln Leu Phe Asn Tyr Val 1265 1270 1275 1280 Ala Thr Ile Pro Asp Asn Ser Ile Val Leu Met Ala Ser Lys Gly Arg                1285 1290 1295 Tyr Val Ser Arg Gly Pro Trp Thr Arg Val Leu Glu Lys Leu Gly Ala            1300 1305 1310 Asp Arg Gly Leu Lys Leu Lys Glu Gln Met Ala Phe Val Gly Phe Lys        1315 1320 1325 Gly Ser Phe Arg Pro Ile Trp Val Thr Leu Asp Thr Glu Asp His Lys    1330 1335 1340 Ala Lys Ile Phe Gln Val Val Pro Ile Pro Val Val Lys Lys Lys Lys 1345 1350 1355 1360 Leu    

Claims (18)

Agents for measuring the expression level of CEMIP (Cell Migration Inducing Hyaluronidase 1) protein or mRNA of the gene encoding the protein; And
A composition for diagnosing cancer, comprising: a CA 19-9 (carbohydrate antigen 19-9) protein or an agent for measuring the expression level of mRNA of a gene encoding the protein. The method of claim 1,
The agent for measuring the expression level of the CEMIP protein comprises one or more selected from the group consisting of antibodies, oligopeptides, ligands, peptide nucleic acid (PNA) and aptamers that specifically bind to the CEMIP protein. , Diagnostic composition for cancer. The method of claim 1,
The agent for measuring the expression level of the CA 19-9 protein is selected from the group consisting of antibodies, oligopeptides, ligands, peptide nucleic acid (PNA) and aptamers that specifically bind to the CA 19-9 protein. A composition for diagnosing cancer, comprising one or more types. The method of claim 1,
The agent for measuring the expression level of the mRNA of the gene encoding the CEMIP protein comprises one or more selected from the group consisting of primers, probes and antisense nucleotides specifically binding to the mRNA of the gene encoding the CEMIP protein, A diagnostic composition for cancer. The method of claim 1,
The agent for measuring the expression level of the mRNA of the gene encoding the CA 19-9 protein is selected from the group consisting of primers, probes and antisense nucleotides that specifically bind to the mRNA of the gene encoding the CA 19-9 protein. Comprising more than one species, the composition for diagnosis of cancer. The method of claim 1,
The cancer is pancreatic cancer, ovarian cancer, colon cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, thyroid cancer, parathyroid cancer, lung cancer, non-small cell lung cancer, prostate cancer, gallbladder cancer, biliary tract cancer, non-Hodgkin's lymphoma, Hodgkin's lymphoma, hematologic cancer , Bladder cancer, kidney cancer, melanoma, colon cancer, bone cancer, skin cancer, head cancer, uterine cancer, rectal cancer, brain tumor, anal muscle cancer, fallopian tube carcinoma, endometrial carcinoma, vaginal cancer, vulvar carcinoma, esophageal cancer, small intestine cancer, endocrine cancer, adrenal cancer , Soft tissue sarcoma, urethral cancer, penile cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS central nervous system tumor, primary CNS lymphoma, spinal cord tumor, brain stem glioma or pituitary adenoma, diagnostic composition for cancer . A diagnostic kit for cancer comprising a diagnostic composition for cancer according to any one of claims 1 to 6. The method of claim 7, wherein
The kit is an RT-PCR kit, DNA chip kit, ELISA kit, protein chip kit, rapid kit or MRM (Multiple reaction monitoring) kit, diagnostic kit for cancer. Measuring the expression level of mRNA of a Cell Migration Inducing Hyaluronidase (CEMIP) protein or a gene encoding the protein in a biological sample isolated from a subject of interest; And
Measuring the expression level of a CA 19-9 (carbohydrate antigen 19-9) protein or mRNA of the gene encoding the protein in a biological sample isolated from a subject of interest. The method of claim 9,
The biological sample includes whole blood, leukocytes, peripheral blood mononuclear cells, white blood cell coat, plasma, serum, sputum, tears tears, mucus, nasal washes, nasal aspirate, breath, urine, semen, saliva, peritoneal washings, Ascites, cystic fluid, meningeal fluid, amniotic fluid, glandular fluid, pancreatic fluid, lymph fluid, pleural fluid, nipple Nipple aspirate, bronchial aspirate, synovial fluid, joint aspirate, organ secretions, cells, cell extracts or cerebrospinal fluid ( Informational method for diagnosing cancer, a cerebrospinal fluid. The method of claim 9,
The expression level of mRNA of the CEMIP protein or gene encoding the same as measured for the biological sample of the subject; And the expression level of mRNA of the CA 19-9 protein or a gene encoding the same; If at least one of the increased compared to the normal control, comprising the step of predicting a high probability of the cancer, information providing method for diagnosis of cancer. The method of claim 9,
The expression level of the CEMIP protein measured in the biological sample of the subject of interest is at least 0.218 ng / ml; And when the expression level of CA 19-9 protein is at least 37 U / ml; If at least one of the, comprising the step of predicting a high probability of the cancer, comprising: providing information for diagnosing cancer. The method of claim 9,
The cancer is pancreatic cancer, ovarian cancer, colon cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, thyroid cancer, parathyroid cancer, lung cancer, non-small cell lung cancer, prostate cancer, gallbladder cancer, biliary tract cancer, non-Hodgkin's lymphoma, Hodgkin's lymphoma, hematologic cancer , Bladder cancer, kidney cancer, melanoma, colon cancer, bone cancer, skin cancer, head cancer, uterine cancer, rectal cancer, brain tumor, anal muscle cancer, fallopian tube carcinoma, endometrial carcinoma, vaginal cancer, vulvar carcinoma, esophageal cancer, small intestine cancer, endocrine cancer, adrenal cancer Diagnosis of cancer, soft tissue sarcoma, urethral cancer, penile cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS central nervous system tumor, primary CNS lymphoma, spinal cord tumor, brain stem glioma or pituitary adenoma How to Provide Information A method of providing information for predicting the prognosis of a cancer comprising measuring the expression level of a Cell Migration Inducing Hyaluronidase 1 (CEMIP) protein or mRNA of a gene encoding the protein in a biological sample isolated from a subject of interest. The method of claim 14,
The biological sample includes whole blood, leukocytes, peripheral blood mononuclear cells, white blood cell coat, plasma, serum, sputum, tears tears, mucus, nasal washes, nasal aspirate, breath, urine, semen, saliva, peritoneal washings, Ascites, cystic fluid, meningeal fluid, amniotic fluid, glandular fluid, pancreatic fluid, lymph fluid, pleural fluid, nipple Nipple aspirate, bronchial aspirate, synovial fluid, joint aspirate, organ secretions, cells, cell extracts or cerebrospinal fluid ( Informational method for predicting the prognosis of cancer, a cerebrospinal fluid. The method of claim 14,
Predicting that the prognosis will be poor when the expression level of the CEMIP protein measured on the biological sample of the subject of interest is 0.429 ng / ml or more, the method of providing information for predicting the prognosis of cancer. The method of claim 14,
Predicting a survival time of 12 months or less when the expression level of the CEMIP protein measured on a biological sample of the subject of interest is 0.429 ng / ml or more, the method of providing information for predicting the prognosis of cancer. The method of claim 14,
The cancer is pancreatic cancer, ovarian cancer, colon cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, thyroid cancer, parathyroid cancer, lung cancer, non-small cell lung cancer, prostate cancer, gallbladder cancer, biliary tract cancer, non-Hodgkin's lymphoma, Hodgkin's lymphoma, hematologic cancer , Bladder cancer, kidney cancer, melanoma, colon cancer, bone cancer, skin cancer, head cancer, uterine cancer, rectal cancer, brain tumor, anal muscle cancer, fallopian tube carcinoma, endometrial carcinoma, vaginal cancer, vulvar carcinoma, esophageal cancer, small intestine cancer, endocrine cancer, adrenal cancer , Soft tissue sarcoma, urethral cancer, penile cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS central nervous system tumor, primary CNS lymphoma, spinal cord tumor, brain stem glioma or pituitary adenoma, How to provide information to make predictions.

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