KR102584898B1 - Methods for diagnosis about endometrial carcinoma and kit using the same - Google Patents

Abstract

The present specification includes measuring the expression rate of Nectin-4 in a biological sample isolated from an individual; And a method for diagnosing endometrial cancer using the nectin-4 expression rate, which includes determining whether an individual develops endometrial cancer based on the measured expression rate of nectin-4, and a kit using the same are provided. According to the present invention, there is an effect of providing a new biomarker that can diagnose, predict, and evaluate endometrial cancer.

Description

Endometrial cancer diagnosis method and kit using the same {METHODS FOR DIAGNOSIS ABOUT ENDOMETRIAL CARCINOMA AND KIT USING THE SAME}

The present invention relates to a method for diagnosing endometrial cancer and a kit using the same.

Endometrial cancer is cancer that occurs in the endometrium that covers the space within the uterus. The prognosis is known to be positive when diagnosed early, but continuous management is essential because the risk of metastasis and recurrence is high.

Endometrial cancer is a different type of cancer that is distinct from cervical cancer and ovarian cancer. When it occurs at the entrance to the uterus, it is called cervical cancer, when it occurs in the body part of the upper part of the uterus, it is called endometrial cancer, and when it occurs in the ovaries on the left and right sides of the uterus, it is called ovarian cancer. do.

In particular, among epithelial ovarian cancers, which account for the largest proportion of ovarian cancers, endometrioid adenocarcinoma has a name similar to endometrial cancer, but endometrioid carcinoma is endometrial cancer. It is a different cancer that is distinct from (endometrial cancer).

Currently, the diagnosis of endometrial cancer is, in most cases, performed through ultrasound and endometrial cell smears. The thickness of the endometrium is measured through ultrasound, and endometrial tissue is obtained and cells are identified through a microscope. is performed. However, endometrial cancer diagnostic testing is not as easy and inexpensive as a blood test, and endometrial cancer cannot be diagnosed with a cervical cytology test.

Therefore, the diagnosis of endometrial cancer is currently performed on patients who visit the hospital because of symptoms, and cancer diagnosis is often delayed.

Therefore, early diagnosis of endometrial cancer is possible even if there are no symptoms, and a biomarker with high diagnostic accuracy is needed.

The technology behind the invention has been written to facilitate easier understanding of the invention. It should not be understood as an admission that matters described in the technology underlying the invention exist as prior art.

The present inventors noted that the relationship between endometrial cancer development and nectin-4 expression in endometrial carcinoma (EC) is not yet known.

Accordingly, the present inventors compared the copy number (Log2 copy number units) of nectin genes including nectin-1, nectin-2, and nectin-4 in endometrial carcinoma (EC) with the normal group (Normal). , it was found that the copy number of the nectin-4 gene in endometrial cancer (EC) was significantly increased compared to the normal group.

Furthermore, the present inventors noted that the nectin-4 expression rate can be effective in diagnosing endometrial cancer, and as a result, they were able to develop a method of providing information on the diagnosis of endometrial cancer using the nectin-4 expression rate.

Accordingly, the problem to be solved by the present invention is to measure the expression rate of Nectin-4 in biological samples isolated from an individual, and to diagnose endometrial cancer in an individual based on the measured Nectin-4 expression rate. The goal is to provide endometrial cancer diagnosis methods and kits using the same, which are configured to provide information about endometrial cancer.

The problems of the present invention are not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

In order to solve the problems described above, the present invention provides a step of measuring the expression rate of nectin-4 in a biological sample isolated from an individual, and measuring the expression rate of nectin-4 in the uterus of the individual based on the measured expression rate of nectin-4. A method for diagnosing endometrial cancer using the nectin-4 expression rate, including the step of determining whether endometrial cancer has occurred, is provided.

As used herein, the term “individual” may refer to an animal, including a human, for which it is intended to be diagnosed with a cancerous disease, including endometrial cancer, and may be used interchangeably with terms such as host, subject, and patient.

The term “endometrial carcinoma (EC)” used in the present name may refer to a malignant cancer or malignant tumor with metastatic properties that arises in the body part belonging to the upper part of the uterus.

The term “endometrial intraepithelial neoplasia (EIN)” used in this specification refers to a benign cancer that does not grow beyond a certain size and does not metastasize to other tissues. It can mean cancer or benign tumor.

The term “Nectin-4” used herein may refer to the nectin-4 protein or a gene encoding the nectin-4 protein. Nectin-4 protein, also known as poliovirus receptor-related-4 (PVRL4), is a transmembrane protein of approximately 52 kDa in size.

The term "nectin-4 expression rate" used herein is expressed as a ratio of the number of cells expressing nectin-4 among cells collected from a biological sample isolated from an individual, preferably an endometrial tissue sample. In this case, the ratio may be expressed as a percentage (%), but is not limited thereto.

The term “nectin-4 expression rate measurement” used herein may mean measuring the level of nectin-4 protein or mRNA of its gene.

As used herein, the term “diagnosis” means confirming the presence or characteristics of a pathological condition. For the purpose of the present invention, diagnosis is to confirm the occurrence of endometrial cancer, and the occurrence of endometrial cancer can be confirmed early based on the nectin-4 expression rate.

As used herein, the term “gene copy number” refers to the number of copies of a nucleic acid molecule in a cell. Gene copy number includes the number of gene copies in a cell's genomic (chromosomal) DNA. Gene copy number in normal cells (non-tumor cells) is normally 2 copies (1 copy for each member of a chromosome pair). The gene copy number often includes half the gene copy number obtained from a sample of the cell population.

According to a feature of the present invention, the step of determining whether the above-mentioned individual develops endometrial cancer includes determining that the above-mentioned individual has endometrial cancer when the measured nectin-4 expression rate is above a predetermined level. More may be included.

According to another feature of the present invention, the above-mentioned nectin-4 expression rate may be the ratio of the number of cells expressing nectin-4 to the number of cells collected from the separated biological sample.

According to another feature of the present invention, the above-mentioned predetermined level may be a nectin-4 expression rate of 0.5% or more in the biological sample.

According to another feature of the present invention, the above-described method for measuring the expression rate of nectin-4 is immunohistochemical staining, RT-PCR, northern blotting, microarray, nuclease protection assay (NPA), or In situ hybridization, ELISA, western blotting, radioimmunoassay, radioimmunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, immunoprecipitation assay, and complement fixation. It may be at least one selected from the group consisting of analysis method, FACS, protein chip kit, and DNA chip kit.

According to another feature of the present invention, the above-described biological sample may be at least one selected from the group consisting of tissue fluid, semen, bone marrow fluid, lymph fluid, tears, nasal discharge, saliva, sweat, milk, blood, serum, plasma, and tissue. there is.

According to another feature of the present invention, the above-described tissue is endometrial tissue, is a biological sample that can be used for immunohistochemical staining, and is selected from the group consisting of frozen tissue sections, paraffin sections, and cell smears. You can.

In order to solve the problems described above, the present invention includes an agent configured to measure the expression rate of nectin-4 in a biological sample isolated from an individual, and based on the measured expression rate of nectin-4, the present invention provides a method for detecting endometrial cancer in an individual based on the measured expression rate of nectin-4. Provided is a kit for providing information on endometrial cancer using the nectin-4 expression rate, which includes a means for providing information on endometrial cancer.

According to a feature of the present invention, the agent configured to measure the nectin-4 expression rate of the kit for providing information on endometrial cancer using the above-described nectin-4 expression rate includes an antibody, an oligopeptide that specifically binds to the nectin-4 protein. It may be at least one of an oligopeptide, a ligand, a peptide nucleic acid (PNA), and an aptamer.

According to a feature of the present invention, the kit for providing information on endometrial cancer using the above-described nectin-4 expression rate may further include an agent for measuring the mRNA expression rate of the gene encoding nectin-4.

According to another feature of the present invention, the agent for measuring the mRNA expression rate of the gene encoding the nectin-4 described above includes primers, probes, and nucleotides that specifically bind to the gene encoding nectin-4. It may be at least one of (nucleotide).

According to another feature of the present invention, the kit for providing information on endometrial cancer using the above-described nectin-4 expression rate may include means for providing prognostic information on endometrial cancer of the above-mentioned individual, One means is a device configured to display information about endometrial cancer, and may include a communication unit for transmitting the expression rate of nectin-4 to a separate computing device to provide information about endometrial cancer.

Furthermore, according to another feature of the present invention, the computing device configured to display information about the above-described endometrial cancer, when the measured expression rate of nectin-4 is above a predetermined level, the endometrium including the nectin-4 expression rate It can provide information that has been determined to be cancer. At this time, the nectin-4 expression rate may be the ratio of the number of cells expressing nectin-4 to the number of cells collected from the separated biological sample. Furthermore, the predetermined level described above may be a percentage of nectin-4 expressing cells in the biological sample of 0.5% or more.

According to another feature of the present invention, the biological sample used in the kit for providing information on endometrial cancer using the above-described nectin-4 expression rate is endometrial tissue, and is a biological sample that can be used for immunohistochemical staining. , may be selected from the group consisting of frozen tissue sections, paraffin sections, and cell smears.

Hereinafter, the present invention will be described in more detail through examples. However, since these examples are only for illustrative purposes of the present invention, the scope of the present invention should not be construed as being limited by these examples.

The present invention has the effect of providing a new biomarker for diagnosing, predicting, and evaluating endometrial cancer.

In addition, the present invention provides a kit that includes an agent configured to measure the expression rate of nectin-4 in a biological sample isolated from an individual, and informs whether the individual develops endometrial cancer based on the measured expression rate of nectin-4. More can be provided.

Furthermore, the present invention classifies normal groups and endometrial cancer patients according to the nectin-4 expression rate, obtains a probability value, calculates a cutoff value based on sensitivity, specificity, and ROC curve, and then determines the endometrial cancer with high accuracy. A method comprising determining whether cancer has occurred may be provided.

In addition, when using the biomarker provided by the present invention, endometrial cancer can be diagnosed early with greater ease and accuracy, thereby contributing to increasing the survival rate of endometrial cancer patients.

The effects according to the present invention are not limited to the contents exemplified above, and further various effects are included in the present specification.

Figure 1 exemplarily illustrates the procedures of a method for providing information on endometrial cancer according to various embodiments of the present invention.
Figure 2 shows the results showing the copy number (Log2 copy number units) of the nectin-4 gene in endometrial carcinoma (EC) compared to the normal group.
Figure 3a shows immunity against nectin-4 expressed in normal endometrial tissue, endometrial intraepithelial neoplasia (EIN) tissue, and endometrial cancer (Endothelial carcinoma (EC)) tissue according to various embodiments of the present invention. This shows the results of immunohistochemical staining (IHC).
Figure 3b is a result showing the ratio of nectin-4 expressing cells in the normal endometrial group (Normal), endometrial benign cancer group (EIN), and endometrial cancer group (EC) according to various embodiments of the present invention.
Figure 4a shows the nectin-4 expression rate predicted using the optimal cutoff value obtained through the Youden index method in the receiver operating characteristic (ROC) curve according to various embodiments of the present invention. It indicates the accuracy of endometrial cancer prediction according to .
Figure 4b shows the cutoff value, sensitivity, specificity, and positive predictive value of the ROC curve for predicting endometrial cancer according to the nectin-4 expression rate according to various embodiments of the present invention. value, PPV) and negative predictive value (NPV).

The advantages and features of the present invention and methods for achieving them will become clear by referring to the embodiments described in detail below along with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and will be implemented in various different forms, but the present embodiments only serve to ensure that the disclosure of the present invention is complete and are within the scope of common knowledge in the technical field to which the present invention pertains. It is provided to fully inform those who have the scope of the invention, and the present invention is only defined by the scope of the claims.

As used in this document, the expression “configured to” depends on the situation, for example, “suitable for,” “having the capacity to.” ," can be used interchangeably with "designed to," "adapted to," "made to," or "capable of."

Terms used in this document are merely used to describe specific embodiments and may not be intended to limit the scope of other embodiments. Singular expressions may include plural expressions, unless the context clearly dictates otherwise. Terms used herein, including technical or scientific terms, may have the same meaning as generally understood by a person of ordinary skill in the technical field described in this document. Among the terms used in this document, terms defined in general dictionaries may be interpreted to have the same or similar meaning as the meaning they have in the context of related technology, and unless clearly defined in this document, have an ideal or excessively formal meaning. It is not interpreted as In some cases, even terms defined in this document cannot be interpreted to exclude embodiments of this document.

Each feature of the various embodiments of the present invention can be partially or fully combined or combined with each other, and as can be fully understood by those skilled in the art, various technical interconnections and operations are possible, and each embodiment may be implemented independently of each other. It may be possible to conduct them together due to a related relationship.

Hereinafter, with reference to FIG. 1, the procedures of the endometrial cancer diagnosis method according to various embodiments of the present invention will be described in detail.

Figure 1 exemplarily illustrates the procedures of an endometrial cancer diagnosis method according to various embodiments of the present invention.

Referring to Figure 1, the endometrial cancer diagnosis method according to various embodiments of the present invention first measures the expression rate of nectin-4 (Nectin-4) in a biological sample isolated from an individual (S110), and the measured nectin It is configured to determine whether an individual develops endometrial cancer based on the expression rate of -4 (S120).

According to various embodiments of the present invention, measuring the expression rate of nectin-4 may mean measuring the level of protein of nectin-4 or mRNA of its gene.

Furthermore, nectin-4 overexpression may mean that the percentage of positive cells expressing nectin-4 is greater than a predetermined reference value.

According to various embodiments of the present invention, endometrial cancer may include cancer characterized by overexpression of nectin-4 protein. However, it is not limited to this and may include cancers in which nectin-4 is overexpressed and has a physiological state characterized by uncontrolled cell growth. For example, cancers for which information may be provided in the present disclosure include colon cancer, pancreatic cancer, stomach cancer, liver cancer, cervical cancer, thyroid cancer, parathyroid cancer, lung cancer, non-small cell lung cancer, prostate cancer, gallbladder cancer, biliary tract cancer, and non-Hodgkin's lymphoma. , Hodgkin lymphoma, blood cancer, bladder cancer, kidney cancer, melanoma, colon cancer, bone cancer, skin cancer, head cancer, uterine cancer, rectal cancer, brain tumor, perianal cancer, fallopian tube carcinoma, vaginal cancer, vulvar carcinoma, esophageal cancer, small intestine cancer, and endocrine cancer. At least one selected from the group consisting of adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, ureteral cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, primary CNS lymphoma, spinal cord tumor, brainstem glioma, or cerebral pituitary adenoma. It may include, but preferably, it may be endometrial cancer.

Here, according to various embodiments of the present invention, the agent for measuring the mRNA expression rate may be at least one of a primer, a probe, and a nucleotide that specifically binds to the gene encoding nectin-4. there is.

Furthermore, the agent for measuring the expression rate of the nectin-4 protein includes at least an antibody, oligopeptide, ligand, PNA (peptide nucleic acid), and aptamer that specifically binds to the nectin-4 protein. It can be composed of one.

Furthermore, referring to Figure 1, in the step of determining whether an individual develops endometrial cancer, the nectin-4 expression rate is determined by expressing nectin-4 among cells collected from a biological sample isolated from the individual, preferably an endometrial tissue section. The number of cells may be expressed as a ratio, and when the measured nectin-4 expressing cells are more than 0.5%, it can be determined that the individual has developed endometrial cancer.

However, without being limited, a predetermined value for determining that endometrium cancer has developed may be determined as an expression rate of nectin-4 expressing cells of 0.5% or more, 0.7821% or more, or 1% or more.

At this time, the nectin-4 expression rate was measured using immunohistochemical staining, RT-PCR, northern blotting, microarray, nuclease protection assay (NPA), or in situ hybridization. , ELISA, western blotting, radioimmunoassay, radioimmunodiffusion method, Ouchterlony immunodiffusion method, rocket immunoelectrophoresis, immunoprecipitation assay, complement fixation assay, FACS, protein chip kit, DNA chip. It can be measured by selecting from a kit.

Furthermore, the biological sample used to measure the nectin-4 expression rate may be tissue fluid, semen, bone marrow fluid, lymph fluid, tears, nasal discharge, saliva, sweat, milk, blood, serum, plasma, and tissue, but is preferably endometrial tissue. It is a biological sample that can be used for immunohistochemical staining, and endometrial tissue can be processed into one of frozen tissue sections, paraffin sections, and cell smears to measure the nectin-4 expression rate.

According to the above procedure, the endometrial cancer diagnosis method using the nectin-4 expression rate according to various embodiments of the present invention can provide information that can increase the accuracy of endometrial cancer diagnosis by measuring the expression rate of nectin-4. Furthermore, a kit for providing information on endometrial cancer using the above diagnostic method can be provided.

Figure 2 shows the copy number (Log2 copy number units) of the nectin-4 gene in endometrial carcinoma (EC) analyzed from public data extracted from The Cancer Genome Atlas (TCGA) program of the U.S. National Cancer Institute (NCI). ) is the result compared to the normal group (Normal). Referring to Figure 2, nectin-1 and nectin-2 are known to be involved in cell-cell adhesion in poliovirus receptor-related protein 4 (PVRL4), such as nectin-4. Nectin-1 and nectin-3 interact at synapses, and it is known that nectin-1 is mainly found on the axonal side and nectin-3 on the dendritic side in neural tissue in the early and aging stages of brain development.

Referring to Figure 2, the copy number of the nectin-4 gene in endometrial cancer (EC) is statistically significantly (p<0.0001) significantly increased compared to the normal group (Normal).

Accordingly, the present inventors focused on the copy number of the nectin-4 gene, which showed a statistically significant difference (p<0.0001) between the endometrial cancer (EC) group and the normal group, and found that nectin-4 was used to diagnose endometrial cancer. It was discovered that it can serve as a biomarker for

Example 1. Immunohistochemical staining (IHC) results for nectin-4

Furthermore, the inventors of the present invention sought to verify the expression rate of nectin-4 in endometrial cancer as a biomarker derived through the above-described process.

Figure 3a shows immunity against nectin-4 expressed in normal endometrial tissue, endometrial intraepithelial neoplasia (EIN) tissue, and endometrial cancer (Endothelial carcinoma (EC)) tissue according to various embodiments of the present invention. Shows the results of immunohistochemical staining (IHC).

Referring to FIG. 3A, nectin-4 in FIG. 3A appears stained yellow, and nectin-4 stained blue represents the nucleus of the cell. “Cytoplasmic & membrane” shown on the right side of Figure 3a indicates that the yellow-stained areas in (A), (B), and (C) of Figure 3a are nectin-4 proteins expressed in the cytoplasm and cell membrane. “Cytoplasmic” shown on the right indicates that the yellow-stained area in (D), (E), and (F) of Figure 3a is the nectin-4 protein expressed in the cytoplasm.

Referring again to Figure 3a, the expression rate of nectin-4 is the normal endometrial tissue ((A) and (D) in Figure 3a) and endometrial benign cancer (EIN) tissue ((B) and (in Figure 3a) It appears higher in endometrial cancer (EC) tissue ((C) and (F) of Figure 3a) compared to E)).

Figure 3b shows the ratio (%) of nectin-4 expressing cells in endometrial tissue in normal endometrial patients (Normal), endometrial benign cancer patients (EIN), and endometrial cancer patients (EC) according to various embodiments of the present invention. This result shows (of positive cells, intensity > weak, low).

At this time, the nectin-4 expression rate was measured using the Nectin-4 ELISA kit from an American R&D company.

Referring to Figure 3b, the median value of the endometrial cancer patient group (EC) represents a % of positive cells expressing nectin-4 of 23.615%. In other words, this may mean that 23.615% of the cells in the endometrial tissue in the endometrial cancer patient group (EC) are nectin-4 expressing cells. The ratio of nectin-4 expressing cells of 23.615% in the endometrial cancer group shows a clear difference compared to the median value (0%) of the normal group, which has almost no nectin-4 expressing cells, and shows a clear difference in the endometrial cancer group. Even when compared to the median value of 3.87% in the benign cancer group (EIN), the percentage of cells expressing nectin-4 is clearly higher.

In other words, the proportion of nectin-4 expressing cells in endometrial tissue is higher in the endometrial cancer group (EC) than in the normal endometrial group (Normal) and the endometrial benign cancer group (EIN) (p<0.0001).

< Immunohistochemical staining and measurement method for nectin-4 >

To confirm the expression rate of nectin-4 in endometrial tissue, we attempted to perform immunohistochemical staining of the endometrial tissue. For this purpose, a tissue microarray (TMA) of the endometrial tissue was first sectioned. Next, 5-μm-thick tissue microarray (TMA) sections obtained through tissue microarray sectioning were deparaffinized in xylene and rehydrated in a series of graded ethanol. In the present invention, the sample obtained through the above process was used as a biological sample.

Heat-mediated antigen retrieval of TMA sections was then performed using a pressure chamber (Pascal; Dako, Carpinteria, CA, USA) after treatment with citrate buffer at pH 6.0.

Next, the sample was immersed in 3% hydrogen peroxide solution (Dako) for 20 minutes at room temperature to inhibit endogenous peroxidase activity, and then the TMA section slide was incubated with mouse monoclonal anti-Nectin-4 antibody (Santa Cruz) for 1 hour at room temperature. Biotechnology, Dallas, TX, USA).

Then, for confirmation of immunohistochemically stained nectin-4 protein, the slides were stained with Envision+Ms HRP link secondary (Dako), visualized with 3,3'-diaminobenzidine (Dako), and stained with hematoxylin. The immunostained slides were then scanned using an Aperio AT2 digital scanner (Leica Biosystems, Vista, CA) and image analyzed with Visiopharm Digital Image Analysis (DIA) software v6.9.1 (Visiopharm, Hø?rsholm, Denmark).

In the present invention, the nectin-4 expression rate was expressed as the percentage (0-100%) of cells expressing nectin-4 compared to the number of cells collected from the biological sample.

Example 2. Accuracy of endometrial cancer prediction according to nectin-4 expression rate

Figure 4a shows the nectin-4 expression rate predicted using the optimal cutoff value obtained through the Youden index method in the receiver operating characteristic (ROC) curve according to various embodiments of the present invention. It indicates the accuracy of endometrial cancer prediction according to . The number of normal groups used in statistics is 87, and the number of endometrial cancer groups (EC), which is the test group, is 320.

Figure 4b shows the cutoff value, sensitivity, specificity, and positive predictive value of the ROC curve of Figure 4a for predicting endometrial cancer according to the nectin-4 expression rate according to various embodiments of the present invention. (Positive predictive value, PPV) and negative predictive value (NPV).

According to Figure 4a, when the cutoff value of the percentage of positive cells expressing nectin-4 for determining the occurrence of endometrial cancer is 0.7821%, it shows a high value of AUC = 0.922, When the nectin-4 expression rate in endometrial cancer is 0.7821% or higher, the probability of endometrial cancer is high.

Referring to Figure 4b, sensitivity is 82.81%, specificity is 95.4%, positive predictive value (PPV) is 98.5%, and negative predictive value (NPV) is 60.1%. represents. Here, sensitivity refers to the probability of determining positive for a positive individual, and specificity refers to the probability of determining negative for a negative individual. Furthermore, positive predictive value (PPV) represents the probability that the disease actually exists when the test result is positive, and negative predictive value (NPV) represents the probability that the disease actually does not exist when the test result is negative. means.

Accordingly, the present invention may further include a step of determining whether endometrial cancer develops based on a model that classifies the normal group and endometrial cancer patients in FIGS. 4A and 4B according to the nectin-4 expression rate.

As a result of the above examples, it can be seen that the patient group with a high nectin-4 expression rate, that is, a high proportion of nectin-4 expressing cells, shows a nectin-4 expression rate higher than the cutoff value compared to the normal group.

Accordingly, it was confirmed that nectin-4 is a specific molecular marker that shows a high expression rate specifically for endometrial cancer, especially endometrial cancer including nectin-4 expression, that is, nectin-4-expressing endometrial cancer. At this time, the biological sample for diagnosing endometrial cancer may be endometrial tissue. In other words, measuring the nectin-4 expression rate in endometrial tissue has the effect of diagnosing endometrial cancer with higher accuracy.

In addition, the present invention provides a kit that includes an agent configured to measure the expression rate of nectin-4 in a biological sample isolated from an individual, and informs whether the individual develops endometrial cancer based on the measured expression rate of nectin-4. More can be provided.

Each of the features of the various embodiments of the present invention can be combined or combined with each other, partially or entirely, and as can be fully understood by those skilled in the art, various technical interconnections and operations are possible, and each embodiment may be implemented independently of each other. and may be implemented together due to a related relationship.

Although embodiments of the present invention have been described in more detail with reference to the accompanying drawings, the present invention is not necessarily limited to these embodiments, and various modifications may be made without departing from the technical spirit of the present invention. . Accordingly, the embodiments disclosed in the present invention are not intended to limit the technical idea of the present invention, but are for illustrative purposes, and the scope of the technical idea of the present invention is not limited by these embodiments. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive. The scope of protection of the present invention should be interpreted in accordance with the claims below, and all technical ideas within the equivalent scope should be construed as being included in the scope of rights of the present invention.

Claims (16)

Measuring the expression rate of Nectin-4 in an endometrial tissue sample isolated from an individual; and
A method of providing information necessary for diagnosing endometrial cancer using the nectin-4 expression rate, comprising providing information on whether an individual develops endometrial cancer based on the measured expression rate of nectin-4. According to claim 1,
The step of providing information regarding whether the individual develops endometrial cancer,
If the measured nectin-4 expression rate is above a predetermined level,
A method of providing information necessary for diagnosing endometrial cancer using the nectin-4 expression rate, further comprising providing information that the individual has endometrial cancer. According to claim 1,
The nectin-4 expression rate is a ratio of the number of cells expressing nectin-4 to the number of cells collected from the separated endometrial tissue sample. A method of providing information necessary for diagnosing endometrial cancer using the nectin-4 expression rate. According to clause 2,
The predetermined level of the nectin-4 expression rate is,
A method of providing information necessary for diagnosing endometrial cancer using the nectin-4 expression rate, which is 0.5% or more. According to claim 1,
The method for measuring the nectin-4 expression rate is,
Immunohistochemical staining, RT-PCR, northern blotting, microarray, nuclease protection assay (NPA) or in situ hybridization, ELISA, western blotting. at least one selected from the group consisting of blotting, radioimmunoassay, radioimmunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, immunoprecipitation assay, complement fixation assay, FACS, protein chip kit, and DNA chip kit. Hanain, a method of providing information necessary for diagnosing endometrial cancer using nectin-4 expression rate. According to claim 1,
The endometrial tissue sample,
Necessary for diagnosing endometrial cancer using nectin-4 expression rate, further comprising at least one selected from the group consisting of tissue fluid, semen, bone marrow fluid, lymph fluid, tears, nasal discharge, saliva, sweat, milk, blood, serum, plasma, and tissue. How to provide information. According to clause 6,
The endometrial tissue is,
It is a biological sample that can be used for immunohistochemical staining,
A method of providing information necessary for diagnosing endometrial cancer using the nectin-4 expression rate, which is selected from the group consisting of frozen tissue sections, paraffin sections, and cell smears. Comprising an agent configured to measure the expression rate of nectin-4 in an endometrial tissue sample isolated from an individual,
A kit for providing information on endometrial cancer using the nectin-4 expression rate, comprising means for providing information on the development of endometrial cancer in an individual based on the measured nectin-4 expression rate. According to clause 8,
The agent configured to measure the nectin-4 expression rate,
Using the nectin-4 expression rate, at least one selected from the group consisting of antibodies, oligopeptides, ligands, PNA (peptide nucleic acids), and aptamers that specifically bind to the nectin-4 protein. Informational kit about endometrial cancer. According to clause 8,
A kit for providing information on endometrial cancer using the nectin-4 expression rate, further comprising an agent for measuring the mRNA expression rate of the gene encoding the nectin-4. According to claim 10,
An agent for measuring the mRNA expression rate of the gene encoding the nectin-4,
A kit for providing information on endometrial cancer using the nectin-4 expression rate, which is at least one of a primer, a probe, and a nucleotide that specifically binds to the gene encoding the nectin-4. According to clause 8,
The means are:
A device configured to display information about endometrial cancer,
A kit for providing information on endometrial cancer using the nectin-4 expression rate, including a communication unit for transmitting the expression rate of nectin-4 to a separate computing device to provide information on the endometrial cancer. According to claim 12,
The computing device is,
If the measured expression rate of nectin-4 is above a predetermined level,
A kit for providing information on endometrial cancer using the nectin-4 expression rate, which provides information determined as endometrial cancer including nectin-4 expression. According to claim 13,
A kit for providing information on endometrial cancer using the nectin-4 expression rate, wherein the nectin-4 expression rate is the ratio of the number of cells expressing nectin-4 to the number of cells collected from the separated endometrial tissue sample. According to claim 13,
The predetermined level of the nectin-4 expression rate is,
Kit for providing information on endometrial cancer using nectin-4 expression rate of 0.5% or higher. According to clause 8,
The endometrial tissue sample,
It is a biological sample that can be used for immunohistochemical staining,
A kit for providing information on endometrial cancer using the nectin-4 expression rate, selected from the group consisting of frozen tissue sections, paraffin sections, and cell smears.

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