KR20160002582A - Composition for diagnosing lung cancer comprising AIMP2-DX2 protein or fragment thereof - Google Patents

Abstract

The present invention relates to a composition comprising an AIMP2-DX2 protein or a fragment thereof for diagnosing lung cancer and, more specifically, to a composition comprising an AIMP2-DX2 protein or a fragment thereof for diagnosing lung cancer, and to a method for detecting an autoantibody of an AIMP2-DX2 protein for providing information needed for diagnosis of lung cancer, comprising the following steps: detecting an antibody against an AIMP2-DX2 protein from an object-derived sample; and determining the object who has the detected amount of the antibody increased compared with a normal person as a patient having lung cancer, or an object having possiblity to get lung cancer. the composition, method, and kit in the present invention is effective to lung cancer diagnosis by confirming whether lung cancer occurs only with a serum sample of an object.

Description

[0001] The present invention relates to a composition for diagnosing lung cancer comprising AIMP2-DX2 protein or fragments thereof,

The present invention relates to a composition for diagnosing lung cancer comprising AIMP2-DX2 protein or a fragment thereof, and more particularly to a composition for diagnosing lung cancer comprising AIMP2-DX2 protein or a fragment thereof and an antibody against AIMP2-DX2 protein DX2 protein in an amount sufficient to detect the presence of an autoantibody of the AIMP2-DX2 protein in an amount sufficient to diagnose lung cancer, And a method for detecting the same.

Lung cancer is a rapidly growing tumor in Korea due to increased smoking and air pollution. The incidence of lung cancer is third in males after stomach cancer and colorectal cancer, and in females in thyroid cancer, breast cancer, colon cancer, stomach cancer (2011 National Cancer Center). Lung cancer accounts for 10% of total cancer incidence, but lung cancer is number one in both men and women in cancer mortality, and lung cancer mortality accounts for 22.6% of total cancer deaths in 2012. National Cancer Center.

This high mortality rate is due to the fact that most cases of lung cancer are diagnosed to have progressed to stage 3 or more at the time of diagnosis and most cases are difficult to cure. Therefore, early diagnosis of lung cancer and reducing mortality from lung cancer are urgent issues (Wulfkuhle et al., Nat. Rev. Cancer 3, 267-275 (2003)).

To date, several methods have been used to diagnose lung cancer. However, up to now, the size of the tumor, the presence of lymph node metastasis, the biopsy of the lung tumor tissue or lymph nodes, the immunohistochemical analysis, (Manser et al., Curr. Opin. Pulm. Med., 10, 266-271 (2004)).

However, in chest computed tomography, the size of the lung cancer must be at least about 0.1 cm. This time, there is a high probability that cancer has already metastasized to other tissues. The method using bronchoscopy is an endoscope inserted into the bronchus It is possible to observe the inside of the lungs directly, but it has a problem of the spatial limitation that it is difficult to observe the tumor at the distal end of the lung.

In order to overcome the disadvantages of the conventional diagnostic methods, the method of the present invention has been used in the blood of patients as follows: Complete blood count (CBC), serum electrolytes, alkaline phosphatase, albumin, aspartate aminotransferase, alanine transaminase (Fishman et al., Cancer Res., 28, 150-154 (1968)), Nagamine et al., Clin. Chem. 29, 379-381 (1983), Muggia et al., 1, 217-228 (1974)).

Thus, research and development of lung cancer markers are continuing, but there are no commercially available diagnostic markers for lung cancer, and development thereof is necessary.

The inventors of the present invention have found that an autoantibody against AIMP2-DX2 protein is detected in a lung cancer patient while studying a method for effectively diagnosing lung cancer, thereby completing the present invention.

Accordingly, an object of the present invention is to provide a composition for diagnosing lung cancer comprising AIMP2-DX2 protein or a fragment thereof.

Another object of the present invention is (a) a method for detecting an antibody against AIMP2-DX2 protein from a sample derived from a subject; And

(b) detecting an autoantibody of AIMP2-DX2 protein to provide information for diagnosis of lung cancer, comprising determining that the detected antibody amount is greater than that of a normal subject, To provide a method to do so.

Another object of the present invention is to provide a lung cancer diagnostic kit comprising an AIMP2-DX2 protein or fragment thereof.

In order to accomplish the above object, the present invention provides a composition for diagnosing lung cancer comprising AIMP2-DX2 protein or a fragment thereof.

According to another aspect of the present invention, there is provided a method for detecting AIMP2-DX2 protein, comprising: (a) detecting an antibody against AIMP2-DX2 protein from a sample derived from a subject; And (b) determining whether the detected antibody amount is greater than that of a normal subject as lung cancer-susceptible or susceptible individuals, comprising the step of administering an autoantibody of AIMP2-DX2 protein The method comprising:

In order to achieve another object of the present invention, there is provided a lung cancer diagnostic kit comprising an AIMP2-DX2 protein or a fragment thereof.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for diagnosing lung cancer comprising AIMP2-DX2 protein or fragment thereof.

The composition of the present invention is characterized by comprising an AIMP2-DX2 protein or fragment thereof.

Autologous antibodies against AIMP2-DX2 protein are found in lung cancer patients, especially in small cell lung cancer. Therefore, the detection of the autoantibody can diagnose lung cancer. A typical method for detecting the autoantibody is to immobilize a target protein to be an antigen on a fixative, and to react the sample such as blood or serum containing an autoantibody extracted from the subject to confirm whether or not the protein is bound.

The inventors of the present invention have found that an autoantibody to AIMP2-DX2 protein occurs in lung cancer patients, fix AIMP2-DX2 protein to a fixed body, and then react with the serum of the subject so that an autoantibody to AIMP2-DX2 protein Serum levels of AIMP2-DX2 protein were not detected in healthy human serum, and autoantibodies were detected in SCLC or NSCLC patients. This point is first disclosed in the present invention.

Thus, the AIMP2-DX2 protein or fragment thereof can be used for lung cancer diagnostic applications.

The AIMP2-DX2 protein is a mutant in which the region of exon 2 in the AIMP2 protein sequence is deleted.

AIMP2 (ARS-interacting multi-functional protein 2) is one of the proteins involved in the formation of aminoacyl-tRNA synthetases (ARSs) and may be called p38 / JTV-1 or p38. The present inventor has found that a novel function of AIMP2 protein is that the genetic collapse of AIMP2 induces overexpression of c-myc in a previous study and causes neonatal lethality of neuronal mouse with hyperproliferation of alveolar epithelial cell of lung, , And that AIMP2 was induced by TGF-β and transferred to the nucleus and inhibited the expression of c-myc (MJ Kim, B.-J. Park, Y J.-H. Park, JW Kang, SW Lee, JM Han, H.-W. Lee, S. Kim, Nat Genet., 34, 330-336, 2003).

The AIMP2-DX2 protein of the present invention is a mutant in which the region of exon 2 in the AIMP2 protein sequence is deleted. The sequence of the AIMP2 protein (312aa version: AAC50391.1 or GI: 1215669; 320aa version: AAH13630.1, GI: 15489023, BC013630 (2), 329-334 (1995)), as well as a novel overlapping gene, < RTI ID = 0.0 > // 320 aa version: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences, Proc Natl Acad Sci USA 99 (26), 16899-16903 (2002) Is a protein in which the region corresponding to exon 2 is deleted. Korean Patent Application No. 10-2003-0018424 filed by the present inventor describes the therapeutic effect of AIMP2 protein on cancer, and the description of AIMP2 protein described in this patent document is incorporated herein by reference.

The AIMP2-DX2 protein comprises a protein having deletion of the region of the exon 2 in the AIMP2 of the entire sequence, and has an activity equivalent to that of the AIMP2 equivalent (substitution, deletion, insertion, or a combination of the amino acid sequences, Or a functional derivative that has a modification that increases or decreases physicochemical properties, but has substantially equivalent activity to AIMP2) in which the region of exon 2 is deleted.

The AIMP2-DX2 protein contains the amino acid sequence of the exon 2 of the AIMP2 protein or deletes all of these regions in the exon 1, exon 3, exon 4 or both of these regions, including the amino acid sequence of this region, And only a part of the sequence is deleted. Preferably, the AIMP2-DX2 protein of the present invention is a protein in which the amino acid sequence of exon 2 of the AIMP2 protein has been deleted.

In addition, the AIMP2-DX2 protein of the present invention includes not only a protein having a native amino acid sequence thereof but also an amino acid sequence variant thereof within the scope of the present invention. A variant of AIMP2-DX2 protein means a protein having a sequence that differs by deletion, insertion, non-conservative or conservative substitution, or a combination thereof, with the AIMP2-DX2 native amino acid sequence and one or more amino acid residues. Amino acid exchanges in proteins and peptides that do not globally alter the activity of the molecule are known in the art (H. Neurath, R. L. Hill, The Proteins, Academic Press, New York, 1979). The most commonly occurring exchanges involve amino acid residues Ala / Ser, Val / Ile, Asp / Glu, Thr / Ser, Ala / Gly, Ala / Thr, Ser / Asn, Ala / Val, Ser / Gly, Thy / Pro, Lys / Arg, Asp / Asn, Leu / Ile, Leu / Val, Ala / Glu and Asp / Gly.

In some cases, it may be modified by phosphorylation, sulfation, acrylation, glycosylation, methylation, farnesylation, and the like.

A fragment of the AIMP2-DX2 protein of the present invention refers to a peptide or protein comprising a partial amino acid sequence of the AIMP2-DX2 protein. The fragment contains a partial amino acid sequence of the AIMP2-DX2 protein, and any fragment can be used as long as it has a structure capable of binding an antibody that specifically binds to AIMP2-DX2 protein.

The AIMP2-DX2 protein or fragment thereof can be prepared by natural extraction or synthesis (Merrifleld, J. Amer. Chem. Soc. 85: 2149-2156, 1963) or by recombinant methods based on DNA sequences Sambrook et al., Molecular Cloning, Cold Spring Harbor Laboratory Press, New York, USA, Second Edition, 1989). When a recombinant technology is used, a nucleic acid encoding AIMP2-DX2 is inserted into an appropriate expression vector, a host cell is cultured to express AIMP2-DX2 in a transformant transformed with a recombinant expression vector, and then transformed from the transformant And recovering AIMP2-DX2.

Preferably, the AIMP2-DX2 protein of the present invention can be represented by the amino acid sequence of SEQ ID NO: 5 or 6.

The lung cancer of the present invention includes both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Preferably, the lung cancer of the present invention may be small cell lung cancer.

(A) detecting an antibody against AIMP2-DX2 protein from a sample derived from a subject; And (b) determining whether the detected antibody amount is greater than that of a normal subject as lung cancer-susceptible or susceptible individuals, comprising the step of administering an autoantibody of AIMP2-DX2 protein The method comprising:

Hereinafter, the method of the present invention will be described step by step.

(a) detecting an antibody against AIMP2-DX2 protein from a sample derived from a subject;

In step (a), an antibody against AIMP2-DX2 protein is detected from a sample derived from a subject.

The sample derived from the subject is a substance extracted from a person who wants to check whether lung cancer is present, and the kind thereof is not particularly limited.

The sample of the present invention refers to a composition obtained from, or derived from, a subject to be examined for lung cancer, including, for example, an autoantibody identified based on physical, biochemical, chemical or physiological characteristics.

The sample includes blood and other liquid samples of biological origin and tissue samples. The source of the tissue sample may be from a fresh or frozen and / or preserved organ or tissue sample, or a solid tissue from a biopsy or aspirate, blood or any blood components, fluids, and any time during pregnancy or development of the subject Of cells or plasma. The sample of the present invention includes, but is not limited to, whole blood, blood-derived cells, serum, plasma, lymphatic fluid, synovial fluid, cell extract and combinations thereof, preferably serum, plasma or serum, May be serum.

The antibody is preferably an anti-AIMP2-DX2 autoantibody, more preferably an anti-AIMP2-DX2 IgG antibody, to the AIMP2-DX2 protein.

The step of detecting the antibody against the AIMP2-DX2 protein of the present invention is preferably by antigen-antibody binding. This is because an epitope, which is a two to three-dimensional region of an antigen, specifically binds to an antibody. Thus, it is " specific "or " recognizable" or " binding "if the antigen and the antibody are capable of immunologically specific binding to each other. The antigen is preferably the AIMP2-DX2 protein or fragment thereof.

Any known method for detecting the presence of an antibody is possible as a method for detecting an antibody of the method of the present invention. Such methods may be heterogeneous or homogeneous, sequential or concurrent, competitive or non-competitive. U.S. Patent Nos. 5,563,036, 5,627,080, 5,633,141, 5,679,525, 5,691,147, 5,698,411, 5,747,352, 5,811,526, 5,851,778 and 5,976,822 disclose the format and application of several other assay methods Explain. The detection method may be a quantitative configuration to test the concentration or amount of the anti-AIMP2-DX2 autoantibody or a qualitative configuration to test for the presence or absence of the anti-AIMP2-DX2 autoantibody can do.

Preferably, the step (a) of detecting the antibody against the AIMP2-DX2 protein from the sample derived from the subject comprises: (a1) adding a sample derived from the subject to a solid immobilized with the AIMP2-DX2 protein or fragment thereof ; And (a2) detecting an antibody bound to the AIMP2-DX2 protein in the reaction.

The step of detecting the antibody of the present invention may be a method of binding the non-immobilized antigen to the antibody and a method of binding the immobilized antigen and antibody, but preferably a method of binding the non-immobilized antigen to the antibody .

That is, the AIMP2-DX2 protein (antigen), which specifically reacts with the anti-AIMP2-DX2 autoantibody, is bound to a solid body (solid support) To produce a reaction. The antigen is in contact with the immobilized body and is contacted with the non-bound biological sample to form an antigen-antibody bond. Then, by washing the solid body, the reaction sample, such as the antibody not bound to the fixed antigen, is removed. After this treatment, an immune complex is formed between the antigen and the anti-AIMP2-DX2 antibody.

Detection of the present invention more preferably involves adding a conjugate of a secondary antibody (e. G., An anti-human IgG antibody) conjugated with a detectable label to the binding between the secondary antibody conjugate and the anti-AIMP2-DX2 antibody of the immunoconjugate To form a sandwich-type antigen-antibody complex, and then identifying a detectable label conjugated to the secondary antibody bound to the sandwich-type antigen-antibody complex.

 Secondary antibodies include recombinant, synthetically produced immunoglobulin fragments with native immunoglobulins isolated from non-human primates (eg, anti-human IgG murine antibodies, anti-human IgG goat antibodies, etc.).

The labeling of the secondary antibody is preferably a conventional coloring agent which causes a color reaction, and is preferably a coloring agent such as HRP (Horseradish peroxidase), basic alkaline phosphatase, colloidal gold, FITC (Poly-Lysine-fluorescein isothiocyanate Fluorescent material such as Rhodamine-B-isothiocyanate (RITC), and coloring matter (Dye) may be used.

The sandwich assay is described by Schuurs et al. U.S. Patent Nos. 3,791,932 and 4,016,043, and Pankratz, et al., U.S. Patent No. 5,876,935, which identify the detectable label bound to the secondary antibody can be detected by conventional ELISA (enzyme-linked immunosorbent assay ), RIA (radioimmunoassay), sandwich assay, Western blotting on polyacrylamide gel, immunoblot analysis or immunohistochemical staining.

The solid body of the present invention can be used as the solid body of the present invention in all solid supports widely used as means for fixing the AIMP2-DX2 protein or a fragment thereof. Suitable materials for use as a fixture consist of synthetic materials such as polystyrene, polyvinyl chloride, polyamide, or other synthetic polymers and may be used in natural polymers such as cellulose acetate, nitrocellulose, and glass as well as natural polymers such as cellulose ≪ / RTI > The fixture may take the form of a ball, a branch, a tube, and a microcalculation or microtiter plate. In addition, sheet-like structures such as paper strips, small plates, and membranes can be used.

(b) determining that the subject having an increased amount of antibody as compared to the normal amount of the subject is lung cancer-susceptible or susceptible

In step (b), the amount of the anti-AIMP2-DX2 antibody relative to the amount of the anti-AIMP2-DX2 antibody detected in step (a) is judged to be the subject having or susceptible to lung cancer.

The amount of the antibody detected in step (a) refers to the amount of the antibody against the AIMP2-DX2 protein in the sample, that is, the amount of the anti-AIMP2-DX2 autoantibody.

Anti-AIMP2-DX2 autoantibodies are not detected in normal individuals who do not have lung cancer and are detected in lung cancer patients. Especially in patients with small cell lung cancer (SCLC).

Therefore, if an autoantibody of the AIMP2-DX2 protein is detected in a sample of the subject to be highly elevated compared with the level of a normal person, the subject can be judged to have lung cancer or have a high probability of being caught.

The method for detecting an autoantibody of the AIMP2-DX2 protein of the present invention through the above steps can provide information for diagnosis of lung cancer to the subject.

The effects of the present invention are well illustrated in the embodiments of the present invention.

In one embodiment of the present invention, transcription and expression levels of AIMP2-DX2 were measured by culturing various small cell lung cancer and non-small cell lung cancer cell lines. As a result, it was confirmed that AIMP2-DX2 was transcribed and expressed in small cell lung cancer and non-small cell lung cancer cell line, and the level was not different.

In another embodiment of the present invention, sera from patients with small cell lung cancer and non-small cell lung cancer were obtained and the amount of anti-AIMP2-DX2 antibody in the serum was measured using nitrocellulose membrane having AIMP2-DX2 protein attached thereto.

As a result, anti-AIMP2-DX2 antibody was not detected in the control group of healthy human serum, and anti-AIMP2-DX2 antibody was detected in serum of patients with small cell lung cancer and non-small cell lung cancer. In particular, it was confirmed that anti-AIMP2-DX2 antibody was detected at a very high frequency in patients with small cell lung cancer.

The present invention also provides a lung cancer diagnostic kit comprising the AIMP2-DX2 protein or a fragment thereof.

Since the kit of the present invention contains the AIMP2-DX2 protein or fragment thereof, the antibody against the AIMP2-DX2 protein contained in the sample can be detected, thereby enabling the diagnosis of lung cancer for the subject.

The kit of the present invention is characterized in that it comprises an AIMP2-DX2 protein or a fragment thereof, and preferably the AIMP2-DX2 protein or fragment thereof is a solid body capable of immobilizing AIMP2-DX2 protein or a fragment thereof As shown in FIG.

The fixture is as described above.

In addition, the kit of the present invention may further comprise a secondary antibody conjugate conjugated with an autoantibody specifically binding to the AIMP2-DX2 protein, and a detectable label conjugated thereto. The secondary antibody is an antibody that binds to an autoantibody (anti-AIMP2-DX2 antibody), preferably an anti-human IgG antibody, and the detectable label is as described above.

In addition, the kit of the present invention may further comprise an anti-AIMP2-DX2 autoantibody which is known in advance. An anti-AIMP2-DX2 autoantibody that is known in advance can be used to establish a standard curve to measure the amount of anti-AIMP2-DX2 autoantibody that is not quantified in the sample from the subject.

In addition, the kit of the present invention may comprise a suitable substrate, buffer, etc. for antigen-antibody reaction and color development of the label.

INDUSTRIAL APPLICABILITY As described above, the present invention relates to a composition for diagnosing lung cancer comprising AIMP2-DX2 protein or a fragment thereof, a step of detecting an antibody against AIMP2-DX2 protein from a sample derived from a subject, DX2 protein or a fragment thereof, in order to provide information necessary for the diagnosis of lung cancer, including the step of determining whether the subject has lung cancer or who is likely to be suffering from lung cancer, and a method for detecting lung cancer including the AIMP2- Provide a diagnostic kit. The composition, method, and kit of the present invention can confirm the incidence of lung cancer by using only the serum sample of the subject, and thus it is effective for diagnosis of lung cancer.

Figure 1 is a photograph of AIMP2-DX2 expression level measured in various lung cancer cell lines (NSCLC: non-small cell lung cancer cell line: SCLC: small cell lung cancer cell line: H322, H460: NSCLC cell line: H146, H69: SCLC cell line: AIMP2: aminoacyl tRNA synthetase complex-interacting multifunctional protein 2; Actin: actin).
Figure 2 is a photograph of AIMP2-DX2 transcription level measured in various lung cancer cell lines (NSCLC: non-small cell lung cancer cell line; SCLC: small cell lung cancer cell line; A549, H1299, H32, H322, H460: NSCLC cell line; H146, H69: SCLC AIMP2: aminoacyl tRNA synthetase complex-interacting multifunctional protein 2; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase.
Figure 3 is a schematic diagram of an experimental procedure to measure ATMP2-DX2 autoantibody levels in SCLC and NSCLS patient sera. The experimental procedure consists of three steps: one is to prepare the diagnostic membrane, two to react with the patient's serum, and the other to react with the anti-human antibody.
Figure 4 shows the results of measuring the level of AIMP2-DX2 autoantibodies in serum of patients with small cell lung cancer and non-small cell lung cancer (Normal serum, N1 ~ N10: normal serum, SCLC serum, S1 ~ S10: serum of small cell lung cancer patients; NSCLC, L1 to L20: serum of patients with non-small cell lung cancer, Lamin A: lamin A; red samples of anti-AIMP2-DX2 antibodies and black samples of anti-AIMP2-DX2 antibodies) .

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

≪ Example 1 >

Comparison of AIMP2-DX2 expression levels in SCLC and NSCLC cells

<1-1> Cell culture

NSCLC cell lines (A549, H1299, NCI-H23, NCI-H322, NCI-H358 and NCI-H460), HCT116 and HEK293 cell lines were obtained from the American Type Culture Collection And 1% antibiotics in RPMI-1640 medium or Dulbecco's modified Eagle medium.

SCLC cell lines NCI-H69, NCI-H128 and NCI-H146 were purchased from Korean Cell Line Bank (Seoul, Korea) and cultured in RPMI-1640 medium containing 10% fetal bovine serum.

<1-2> AIMP2-DX2 expression level measurement

The cells were suspended in RIPA buffer (150 mM NaCl, 25 mM Tris-Cl, 1% Nonidet P-40, 1% sodium deoxycholate, 0.1% sodium dodecyl sulfate and protease inhibitor cocktail)

Separated protein samples were inactivated by treatment at 95 ° C for 7 minutes and then inactivated by SDS-PAGE according to a conventional method (T. Mahmood, PC Yang, N. Am. J. Med. Science 4: 429-434, 2012) PAGE and Western blotting.

actin antibody (sc-1616, Santa Cruz Biotechnology) was commercially available, and AIMP2 and AIMP2-DX2 antibodies were prepared by conventional antibody preparation methods.

As shown in FIG. 1, the expression level of AIMP2-DX2 was similarly expressed in NSCLC and SCLC cells without significant difference.

<1-3> Measurement of AIMP2-DX2 transcription level

To measure ATMP2-DX2 transcription levels, NSCLCs A549, H1299, H23, H322 and H460 and SCLC H146 and H69 cells were used. ATMP2-DX2 was amplified using primers 1-2 of the nucleotide sequences shown in Table 1 below, and GAPDH was amplified using primers 3 to 4. As shown in FIG. 2, the AIMP2-DX2 transcription level was not different between SCLS and NSCLC cells.

Name of the primer Base sequence SEQ ID NO: Forward ATMP2-DX2 5'-AACGTGCACGGCAGGAGCTAC -3 ' One Reverse ATMP2-DX2 5'-CCAGCTGATAGTCTTGGCGGG -3 ' 2 Forward GAPDH 5'-ATCTTCCAGGAGCGAGATCCC-3 ' 3 Reverse GAPDH 5'-AGTGAGCTTCCCGTTCAGCTC -3 ' 4

< Example  2>

SCLC  And NSCLS  In patient serum AIMP2 - DX2  Autoantibody level measurement

Serum from healthy individuals, SCLC and NSCLC patients was obtained from Bucheon Hospital (schbc-biobank-2011-003). In order to measure anti-AIMP2-DX2 antibody, the level of autoantibody was measured according to the experimental method of [Fig. 3]. Recombinant AIMP2-DX2, lamin A and Snail were attached to nitrocellulose membrane (0.5 ng / well). Each membrane was reacted with a serum sample diluted 1: 1000 in blocking buffer for 1 hour and reacted with anti-human antibody (1: 20,000) conjugated with Horseradish peroxidase for 30 minutes. ECL was used to visualize the binding sites of human antibodies with chemiluminescence and X-ray film exposure.

As shown in FIG. 4, no AIMP2-DX2 autoantibody was detected in the healthy control group, and AIMP2-DX2 autoantibody was detected in the NSCLC or SCLC patient group. In particular, AIMP2-DX2 autoantibody was detected in 8 out of 10 cases in the SCLC patient group, and AIMP2-DX2 autoantibody was detected in serum of SCLC patients in a particularly high frequency.

The present invention relates to a composition for the diagnosis of lung cancer using the AIMP2-DX2 protein, and more particularly to a composition for diagnosing lung cancer comprising ATMP2-DX2 protein, (b) a composition for detecting AIMP2-DX2 protein from a sample derived from a subject, Detecting an antibody; And (c) determining that the subject having an increased amount of the antibody as compared to the normal amount of the subject is an individual who has been or may be susceptible to lung cancer. Also provided is a method for detecting an autoantibody of AIMP2-DX2 protein and a lung cancer diagnostic kit comprising AIMP2-DX2 protein or fragment thereof to provide information necessary for diagnosis of lung cancer. The composition, method, and kit of the present invention can detect the incidence of lung cancer by using only the serum sample of the subject, and thus it is highly effective in the diagnosis of lung cancer and thus is highly industrially applicable.

<110> Pusan National University Industry-University Cooperation Foundation <120> Composition for diagnosing lung cancer comprising AIMP2-DX2 <130> NP14-0019 <160> 6 <170> Kopatentin 2.0 <210> 1 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> AIMP2-DX2 forward primer <400> 1 aacgtgcacg gcaggagcta c 21 <210> 2 <211> 21 <212> DNA <213> Artificial Sequence <220> &Lt; 223 > AIMP2-DX2 reverse primer <400> 2 ccagctgata gtcttggcgg g 21 <210> 3 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> GAPDH forward primer <400> 3 atcttccagg agcgagatcc c 21 <210> 4 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> GAPDH reverse primer <400> 4 agtgagcttc ccgttcagct c 21 <210> 5 <211> 251 <212> PRT <213> Artificial Sequence <220> <223> AIMP2-DX2 of Homo sapiens <400> 5 Met Pro Met Tyr Gln Val Lys Pro Tyr His Gly Gly Gly Ala Pro Leu   1 5 10 15 Arg Val Glu Leu Pro Thr Cys Met Tyr Arg Leu Pro Asn Val His Gly              20 25 30 Arg Ser Tyr Gly Pro Ala Pro Gly Ala Gly His Val Gln Asp Tyr Gly          35 40 45 Ala Leu Lys Asp Ile Val Ile Asn Ala Asn Pro      50 55 60 Ser Leu Leu Val Leu His Arg Leu Leu Cys Glu His Phe Arg Val Leu  65 70 75 80 Ser Thr Val His Thr His Ser Ser Val Lys Ser Val Pro Glu Asn Leu                  85 90 95 Leu Lys Cys Phe Gly Glu Gln Asn Lys Lys Gln Pro Arg Gln Asp Tyr             100 105 110 Gln Leu Gly Phe Thr Leu Ile Trp Lys Asn Val Pro Lys Thr Gln Met         115 120 125 Lys Phe Ser Ile Gln Thr Met Cys Pro Ile Glu Gly Glu Gly Asn Ile     130 135 140 Ala Arg Phe Leu Phe Ser Leu Phe Gly Gln Lys His Asn Ala Val Asn 145 150 155 160 Ala Thr Leu Ile Asp Ser Trp Val Asp Ile Ala Ile Phe Gln Leu Lys                 165 170 175 Glu Gly Ser Ser Lys Glu Lys Ala Ala Val Phe Arg Ser Ser Met Asn Ser             180 185 190 Ala Leu Gly Lys Ser Pro Trp Leu Ala Gly Asn Glu Leu Thr Val Ala         195 200 205 Asp Val Val Leu Trp Ser Val Leu Gln Gln Ile Gly Gly Cys Ser Val     210 215 220 Thr Val Pro Ala Asn Val Gln Arg Trp Met Arg Ser Ser Cys Glu Asn Leu 225 230 235 240 Ala Pro Phe Asn Thr Ala Leu Lys Leu Leu Lys                 245 250 <210> 6 <211> 243 <212> PRT <213> Artificial Sequence <220> <223> AIMP2-DX2 of Homo sapiens <400> 6 Met Pro Met Tyr Gln Val Lys Pro Tyr His Gly Gly Gly Ala Pro Leu   1 5 10 15 Arg Val Glu Leu Pro Thr Cys Met Tyr Arg Leu Pro Asn Val His Gly              20 25 30 Arg Ser Tyr Gly Pro Ala Pro Gly Ala Gly His Val Gln Asp Tyr Gly          35 40 45 Ala Leu Lys Asp Ile Val Ile Asn Ala Asn Pro      50 55 60 Ser Leu Leu Val Leu His Arg Leu Leu Cys Glu His Phe Arg Val Leu  65 70 75 80 Ser Thr Val His Thr His Ser Ser Val Lys Ser Val Pro Glu Asn Leu                  85 90 95 Leu Lys Cys Phe Gly Glu Gln Asn Lys Lys Gln Pro Arg Gln Asp Tyr             100 105 110 Gln Leu Gly Phe Thr Leu Ile Trp Lys Asn Val Pro Lys Thr Gln Met         115 120 125 Lys Phe Ser Ile Gln Thr Met Cys Pro Ile Glu Gly Glu Gly Asn Ile     130 135 140 Ala Arg Phe Leu Phe Ser Leu Phe Gly Gln Lys His Asn Ala Val Asn 145 150 155 160 Ala Thr Leu Ile Asp Ser Trp Val Asp Ile Ala Ile Phe Gln Leu Lys                 165 170 175 Glu Gly Ser Ser Lys Glu Lys Ala Ala Val Phe Arg Ser Ser Met Asn Ser             180 185 190 Ala Leu Gly Lys Ser Pro Trp Leu Ala Gly Asn Glu Leu Thr Val Ala         195 200 205 Asp Val Val Leu Trp Ser Val Leu Gln Gln Ile Gly Gly Cys Ser Val     210 215 220 Thr Val Pro Ala Asn Val Gln Arg Trp Met Arg Ser Ser Cys Glu Asn Leu 225 230 235 240 Ala Pro Phe            

Claims (8)

A composition for the diagnosis of lung cancer comprising AIMP2-DX2 protein or fragment thereof.
The composition of claim 1, wherein the lung cancer is a small cell lung cancer.
(a) detecting an antibody against AIMP2-DX2 protein from a sample derived from a subject; And
(b) detecting an autoantibody of AIMP2-DX2 protein to provide information for diagnosis of lung cancer, comprising determining that the detected antibody amount is greater than that of a normal subject, How to.
4. The method according to claim 3, wherein the step of (a) detecting the antibody against the AIMP2-DX2 protein from the sample derived from the subject comprises
(a1) adding a sample derived from a subject to a fixed body on which the AIMP2-DX2 protein or a fragment thereof is immobilized, and reacting; And
(a2) detecting an antibody bound to the AIMP2-DX2 protein in the reaction.
4. The method according to claim 3, wherein the sample is a sample selected from the group consisting of blood, plasma, and serum of the subject.
4. The method of claim 3, wherein the lung cancer is a small cell lung cancer.
A lung cancer diagnostic kit comprising AIMP2-DX2 protein or fragment thereof.
[8] The kit according to claim 7, wherein the kit further comprises a secondary antibody conjugate conjugated with an autoantibody specifically binding to AIMP2-DX2 protein and a detectable label conjugated thereto Kits.

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