KR20210015259A - Biomarker composition for diagnosing or prognostic analysis of bladder cancer, kit comprising the same and method for diagnosing bladder cancer using the same - Google Patents

Abstract

The present invention relates to a biomarker composition for bladder cancer diagnosis or prognosis analysis, a kit, and a diagnostic method using the same. More specifically, the present invention relates to the biomarker composition including an agent for measuring the expression level of a protein of soluble FAS and an agent for measuring the expression level of apolipoprotein A1 or matrix metallopeptidase 9 (MMP9) protein as an active ingredient.

Description

A biomarker composition for diagnosing or prognostic analysis of bladder cancer, kit comprising the same and method for diagnosing bladder cancer using the same}

The present invention relates to a biomarker composition, a kit, and a diagnostic method using the same for diagnosis or prognosis of bladder cancer, and in more detail, 2 of soluble FAS (sFAS), apolipoprotein A1 (Apolipoprotein A1) and MMP9 (Matrix metallopeptidase 9). It relates to the use of predicting the diagnosis and prognosis of bladder cancer with multiple diagnosis of species or combinations of three.

Bladder cancer is the most frequently occurring cancer in the urinary system, and it has been reported that 16.5 people per 100,000 people per year in the West, while 4.5 people occur in Korea. As such, the incidence rate is lower than in the West, but the incidence rate is increasing year by year, and in Korea, it is known as the most frequent cancer among urinary system cancers.

Bladder cancer is largely classified into non-muscle invasive bladder cancer and invasive bladder cancer according to the degree of invasion. Non-invasive bladder cancer is a lesion in which the cancer is localized to the mucous membrane without invading the muscle layer.After transurethral resection of bladder tumor, depending on the presence or absence of risk factors, it can be treated relatively simply by injecting an anticancer drug or BCG into the bladder. Recurrence and progression to invasive cancer are problematic. On the other hand, invasive bladder cancer refers to a state in which cancer has penetrated to the muscle layer, and for its treatment, complex urinary diversion must be performed along with radical cystectomy, and may cause fatal results to the patient. Therefore, it is very important to predict recurrence and progression, early detection, and prevention after primary treatment. Therefore, such frequent recurrence and progression of stage is a problem that is frequently raised in bladder cancer, and it is necessary to find an index that can effectively predict the progression of bladder cancer recurrence and invasiveness or to develop a treatment (Korean Patent No. 10-1557183, Bladder cancer prognosis diagnostic marker).

Because bladder cancer has a higher probability of recurrence after treatment compared to other cancers, regular retests are required after surgery (JB Shah, DJ McConkey, CP Dinney, New strategies in muscle-invasive bladder cancer: on the road to personalized medicine, Clin. Cancer Res. 17 (9) (2011) 2608-2612. KN Rayn, GR Hale, GP Grave, PK Agarwal, New therapies in nonmuscle invasive bladder cancer treatment, Indian J. Urol. 34 (1) (2018) 11-19 .). Cystoscopy currently being used has limitations in that the procedure is expensive and the method is invasive, so it can cause pain to the patient (AS Brems-Eskildsen, K. Zieger, H. Toldbod, C. Holcomb, R. Higuchi, F. Mansilla) , L. Dyrskjot, Prediction and diagnosis of bladder cancer recurrence based on urinary content of hTERT, SENP1, PPP1CA, and MCM5 transcripts, BMC Cancer 10 (2010) 646.SF Shariat, JA Karam, Y. Lotan, PI Karakiewizc, Critical evaluation of urinary markers for bladder cancer detection and monitoring, Rev. Urol. 10 (2) (2008) 120-135).

In order to overcome these limitations, there is a growing need to provide a combination of biomarkers for diagnosing bladder cancer with high specificity and sensitivity while being able to conveniently perform non-invasive tests.

Korean Patent Registration No. 10-1557183 (2015.09.24)

Accordingly, an object of the present invention is to provide a biomarker composition, a kit, and a diagnostic method for bladder cancer diagnosis or prognosis analysis that can be predicted with high accuracy by improving the accuracy of the diagnosis and prognosis of bladder cancer with a combination of biomarkers for bladder cancer diagnosis.

Another object of the present invention is to provide a biomarker composition, a kit for diagnosis or prognosis analysis of bladder cancer, and a diagnostic method using the same, which can be conveniently tested non-invasively and have high specificity and sensitivity.

A biomarker composition for diagnosing bladder cancer or analyzing prognosis according to a preferred embodiment of the present invention for achieving the above object comprises: an agent measuring the expression level of a protein of soluble FAS; And an agent for measuring the expression level of a protein of apolipoprotein A1 or matrix metallopeptidase 9 (MMP9) as an active ingredient.

In addition, a biomarker composition for diagnosing bladder cancer or analyzing prognosis according to an embodiment of the present invention includes an agent measuring the expression level of a protein of soluble FAS; An agent for measuring the expression level of the protein of Apolipoprotein A1; And an agent for measuring the expression level of a protein of Matrix metallopeptidase 9 (MMP9) as an active ingredient.

In addition, in the biomarker composition for diagnosis or prognosis analysis of bladder cancer according to the present invention, the agent for measuring the expression level of the protein may be any one selected from the group including antibodies, aptamers, antagonists, and combinations thereof.

In addition, in the biomarker composition for diagnosis or prognosis analysis of bladder cancer according to the present invention, the protein is one or more biological samples selected from the group consisting of tissues, cells, whole blood, serum, plasma, saliva, sputum, and urine obtained from mammals. It may be derived from

In addition, in the biomarker composition for diagnosing bladder cancer or analyzing prognosis according to the present invention, the diagnosis of bladder cancer may include diagnosis of the bladder cancer, including progression and recurrence.

The kit for diagnosing bladder cancer or analyzing prognosis according to a preferred embodiment of the present invention may include the composition.

In addition, in the kit for diagnosis or prognosis of bladder cancer according to the present invention, the kit is a microarray, an aptamer chip kit, an ELISA (enzyme linked immunosorbent assay) kit, a blotting kit, an immunoprecipitation kit. , Immunofluorescence test kit, protein chip kit, and a combination thereof.

A method of providing information necessary for diagnosis or prognosis analysis of bladder cancer according to a preferred embodiment of the present invention includes the steps of: (a) measuring the expression level of a protein of soluble FAS from a biological sample; (b) measuring the expression level of the protein of apolipoprotein A1 or Matrix metallopeptidase 9 (MMP9) from the biological sample; And (c) when the expression level of soluble FAS and apolipoprotein A1 (apolipoprotein A1) protein is high, or when the expression level of soluble FAS and matrix metallopeptidase 9 (MMP9) is high compared to the normal control, it is judged as bladder cancer disease. It may include the step of.

In addition, in the method of providing information necessary for diagnosis or prognosis analysis of bladder cancer according to the present invention, the (b) measurement of the expression level of the protein of apolipoprotein A1 or MMP9 (Matrix metallopeptidase 9) from the biological sample The step of, measuring the expression level of the protein of apolipoprotein A1 (Apolipoprotein A1) from the biological sample; And measuring the expression level of the protein of Matrix metallopeptidase 9 (MMP9) from the biological sample.

In addition, in the method of providing information necessary for diagnosis or prognosis analysis of bladder cancer according to the present invention, the expression level of the protein is measured using any one selected from the group including antibodies, aptamers, antagonists, and combinations thereof. Can be.

In addition, in the method for providing information necessary for diagnosis or prognosis analysis of bladder cancer according to the present invention, the level measurement includes immunoassay, ligand binding assay, MALDI-TOF (Matrix Desorption/Ionization Time of Flight Mass Spectrometry) analysis, SELDI-TOF (Sulface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry) analysis, radioimmunoassay, radioactive immunodiffusion method, octeroni immunodiffusion method, rocket immunoelectrophoresis, complement fixation method, two-dimensional electrophoresis analysis, liquid chromatography Any one method selected from the group consisting of liquid chromatography-Mass Spectrometry (LC-MS), LC-MS/MS (liquid chromatography-Mass Spectrometry/Mass Spectrometry), and ELISA (enzyme linked immunosorbent assay) It may be to use.

In addition, in the method of providing information necessary for diagnosis or prognosis analysis of bladder cancer according to the present invention, the biological sample is 1 from the group consisting of tissues, cells, whole blood, serum, plasma, saliva, sputum and urine obtained from mammals. More than a species is selected, and the bladder cancer diagnosis may include diagnosis of the bladder cancer including progression and recurrence.

According to the present invention, the biomarker composition, kit, and diagnostic method using the same for the diagnosis or prognosis of bladder cancer of the present invention include two types of soluble FAS (sFAS), apolipoprotein A1 (Apolipoprotein A1), and MMP9 (Matrix metallopeptidase 9) or The diagnosis of bladder cancer and the accuracy of the prognosis test can be improved with a combination of three types of multiple diagnosis, so that it can be predicted with high accuracy.

In addition, the prior art uses an invasive cystoscopy and a biomarker in blood for the diagnosis of bladder cancer, but the present invention can provide a method of non-invasively testing a urine sample.

In particular, it is possible to provide a urine biomarker suitable for POCT (on-site diagnosis) or home health care (self-diagnosis) for prognostic management after treatment of bladder cancer with high recurrence.

1 is a graph showing the result of measuring the concentration of MMP9 according to a clinical study according to an embodiment of the present invention.
2 is a graph showing a result of measuring the concentration of apolipoprotein A1 according to a clinical study according to an embodiment of the present invention.
3 is a graph showing the result of measuring the concentration of soluble FAS according to a clinical study according to an embodiment of the present invention.
4 is a graph showing the result of measuring the concentration of soluble FAS according to a clinical study for TURB patients and radical cystectomy patients according to an embodiment of the present invention.
5 is a graph showing the results of performing ROC curve analysis of a combination of two biomarkers of apolipoprotein A1 and MMP9 for sensitivity and specificity.
6 is a graph showing the results of performing ROC curve analysis of a combination of two biomarkers of apolipoprotein A1 and soluble FAS for sensitivity and specificity.
7 is a graph showing the results of performing ROC curve analysis of the two biomarkers of MMP9 and soluble FAS for sensitivity and specificity.
8 is a graph showing the results of performing ROC curve analysis of three biomarkers of apolipoprotein A1, MMP9 and soluble FAS for sensitivity and specificity.

Since the present invention can apply various transformations and have various embodiments, specific embodiments will be described in detail in the detailed description. However, this is not intended to limit the present invention to a specific embodiment, it is to be understood to include all conversions, equivalents, and substitutes included in the spirit and scope of the present invention. In describing the present invention, when it is determined that a detailed description of a related known technology may obscure the subject matter of the present invention, a detailed description thereof will be omitted.

The terms used in the present application are only used to describe specific embodiments, and are not intended to limit the present invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. In the present application, terms such as "comprise" or "have" are intended to designate the presence of features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, but one or more other features. It is to be understood that the presence or addition of elements or numbers, steps, actions, components, parts, or combinations thereof, does not preclude in advance.

Terms such as first and second may be used to describe various components, but the components should not be limited by the terms. These terms are used only for the purpose of distinguishing one component from another component.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the drawings. It is obvious to those skilled in the art that the present invention can be embodied in other specific forms without departing from the spirit and essential features of the present invention.

A biomarker composition for diagnosing bladder cancer or analyzing prognosis according to an embodiment of the present invention includes an agent measuring the expression level of a protein of soluble FAS; And an agent for measuring the expression level of a protein of apolipoprotein A1 or matrix metallopeptidase 9 (MMP9) as an active ingredient.

In addition, a biomarker composition for diagnosing bladder cancer or analyzing prognosis according to an embodiment of the present invention includes an agent measuring the expression level of a protein of soluble FAS; An agent for measuring the expression level of the protein of Apolipoprotein A1; And an agent for measuring the expression level of a protein of Matrix metallopeptidase 9 (MMP9) as an active ingredient.

FAS (CD95, apoptosis antigen 1) is a type of tumor necrosis factor receptor, and FAS ligand is mainly expressed in activated T lymphocytes. When FAS ligand is bound to FAS, a series of intracellular cysteine proteases It is known that is activated and the nucleic acid protein is segmented, resulting in apoptosis.

Soluble FAS (sFAS) is primarily expressed on epithelial cells and activated lymphocytes and regulates T cell homeostasis by mediating the proliferation and death of T lymphocytes. High sFas levels have been associated with several autoimmune disorders, including multiple sclerosis, autoimmune lymphoproliferative syndrome and autoimmune thyroiditis (Hashimoto's thyroiditis).

"Apolipoprotein" is a protein formed by binding to a lipid to form a lipoprotein. These proteins can act as enzyme cofactors, receptor ligands, and lipid transport carriers that regulate the metabolism and absorption of proteins in tissues.

"Apolipoprotein A1" is a protein that is a major protein component of high-density lipoprotein (HDL) in plasma. Apolipoprotein A1 is a cofactor of lecithin cholesterol acyltransferase (LCAT), which is responsible for the formation of most plasma cholesteryl esters. In humans, Apolipoprotein A1 is encoded by the APOAI gene and can be derived from any origin, eg, human, bovine, murine, horse, dog, and the like.

MMP9 (Matrix metallopeptidase 9) is a type of extracellular matrix metal-containing protease (MMP), and MMP is type IV collagenase (MMP2, 9), stromelysin (MMP-3) and interstitial collagenase (MMP-3), depending on substrate preference. MMP-1), and type IV collagenase is divided into gelatinase A (MMP-2, molecular weight 72 kD) and gelatinase B (MMP-9, molecular weight 92 kD), and MMP-9 is produced in both normal and cancer cells. It is known to be closely related to the malignancy of tumor cells.

When using the biomarker composition for diagnosing bladder cancer or prognostic analysis according to the present invention, soluble FAS, apolipoproteins according to the measurement of changes in the expression level of two or three selected from the group consisting of soluble FAS, apolipoprotein A1 and MMP9 Bladder cancer can be diagnosed with remarkably higher accuracy compared to the single markers of A1 and MMP9.

In the present invention, the term "diagnosis" means to confirm the presence or characteristics of a pathological condition. For the purposes of the present invention, the diagnosis means predicting or confirming the prognosis of bladder cancer, and the diagnosis of bladder cancer of the present invention may include diagnosis of the bladder cancer, including progression and recurrence. "Prognosis" means the prediction of the course and outcome of a disease, and in the present invention, it includes predicting the recurrence and progression of bladder cancer.

In the present invention, "biomarker", "marker" or "diagnostic marker" refers to a marker capable of distinguishing normal or pathological conditions, predicting a treatment response, and measuring objectively. In particular, with respect to bladder cancer in the present invention, it means that the protein expression level or gene expression level is significantly increased or decreased in an individual having a bladder cancer disease or a possibility (risk) compared to a normal control group.

In the present invention, "measurement of the expression level of a protein" refers to a process of confirming the presence and expression of a bladder cancer diagnostic marker (protein) or a gene encoding the same in a biological sample in order to diagnose bladder cancer. The agent for measuring the expression level of the above protein may be any one selected from the group containing antibodies, aptamers, antagonists, and combinations thereof. Specifically, the formulation includes an antibody specific for a protein encoded by a gene, which means a specific protein molecule directed against an antigenic site, and includes all of polyclonal antibodies, monoclonal antibodies, and recombinant antibodies.

For the measurement of the expression level of the protein, quantitative and qualitative analysis methods known in the art may be used, for example, enzyme immunoassay (ELISA), radioimmunoassay (RIA), and sandwich assay. ), Western Blotting, Immunoprecipitation, Immunohistochemical Staining, Fluorescence Immunization, Enzyme Substrate Coloring, Antigen-Antibody Aggregation, Flow Cytometry (Fluorescence Activated Cell Sorter, FACS), Mass Spectrometry Method , MRM (Multiple Reaction Monitoring) analysis, multiple amine-specific stable isotope experiments (iTRAQ, Isobaric tags for relative and absolute quantitation), or protein chip, and the like, but is not limited thereto.

At this time, the protein is derived from one or more biological samples selected from the group consisting of tissues, cells, whole blood, serum, plasma, saliva, sputum, and urine obtained from mammals.

The kit for diagnosing or prognosing bladder cancer according to an embodiment of the present invention includes an agent for measuring the expression level of a soluble FAS protein; And an agent for measuring the expression level of a protein of apolipoprotein A1 or MMP9 (Matrix metallopeptidase 9); a biomarker composition for diagnosis or prognosis analysis of bladder cancer comprising as an active ingredient.

In addition, the kit according to the present invention comprises an agent for measuring the expression level of a soluble FAS protein; An agent for measuring the expression level of the protein of Apolipoprotein A1; And it may include a biomarker composition for diagnosing bladder cancer or analyzing the prognosis comprising a; and an agent for measuring the expression level of the protein of MMP9 (Matrix metallopeptidase 9) as an active ingredient.

The kit according to the present invention can diagnose bladder cancer-related diseases by quantitatively or qualitatively analyzing proteins, and methods for measuring proteins include enzyme immunoassay (ELISA), radioimmunoassay (RIA), and sandwich assay. ), Western Blotting, Immunoprecipitation, Immunohistochemical Staining, Fluorescence Immunization, Enzyme Substrate Coloring, Antigen-Antibody Aggregation, Flow Cytometry (Fluorescence Activated Cell Sorter, FACS), Mass Spectrometry Method , MRM (Multiple Reaction Monitoring) analysis, multiple amine-specific stable isotope experiments (iTRAQ, Isobaric tags for relative and absolute quantitation), or protein chip (protein chip) can be measured.

For example, the diagnostic kit of the present invention may contain essential elements necessary to perform ELISA. The ELISA kit contains antibodies specific for these proteins. Antibodies are antibodies having high specificity and affinity for a marker protein and little cross-reactivity with other proteins, and are monoclonal, polyclonal, or recombinant antibodies. In addition, the ELISA kit may contain an antibody specific for a control protein. Other ELISA kits include reagents capable of detecting bound antibodies, such as labeled secondary antibodies, chromophores, enzymes (e.g., conjugated with antibodies), and their substrates or antibodies capable of binding. Other materials may be included.

The kit according to the present invention is not limited thereto, and a microarray, an aptamer chip kit, an ELISA (enzyme linked immunosorbent assay) kit, a blotting kit, an immunoprecipitation kit, an immunofluorescence test kit, a protein chip It may be selected from the group consisting of kits and combinations thereof.

A method of providing information necessary for diagnosis or prognosis analysis of bladder cancer according to an embodiment of the present invention includes the steps of: (a) measuring the expression level of a soluble FAS protein from a biological sample; (b) measuring the expression level of the protein of apolipoprotein A1 or Matrix metallopeptidase 9 (MMP9) from the biological sample; And (c) when the expression level of soluble FAS and apolipoprotein A1 (apolipoprotein A1) protein is high, or when the expression level of soluble FAS and matrix metallopeptidase 9 (MMP9) is high compared to the normal control, it is judged as bladder cancer disease. It may include the step of.

In the present invention, the "biological sample" of step (a) includes a sample whose protein expression level or gene expression level is different according to bladder cancer-related diseases, and specifically, tissues, cells, and cells obtained from mammals It means at least one selected from the group consisting of whole blood, serum, plasma, saliva, sputum, and urine, and the biological sample may be isolated from the human body.

The expression level of the protein in step (a) can be measured using any one selected from the group including antibodies, aptamers, antagonists, and combinations thereof. In addition, protein expression level measurements include immunoassay, ligand binding assay, MALDI-TOF (Matrix Desorption/Ionization Time of Flight Mass Spectrometry) analysis, SELDI-TOF (Sulface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry) analysis, Radiation Immunoassay, Radioimmune Diffusion Method, Okteroni Immune Diffusion Method, Rocket Immunoelectrophoresis, Complement Immobilization Assay, 2D Electrophoresis Analysis, Liquid Chromatography-Mass Spectrometry, LC-MS, LC- Any one method selected from the group consisting of MS/MS (liquid chromatography-Mass Spectrometry/Mass Spectrometry), and ELISA (enzyme linked immunosorbent assay) may be used, but is not limited thereto.

The step of measuring the expression level of apolipoprotein A1 (Apolipoprotein A1) or MMP9 (Matrix metallopeptidase 9) protein from the biological sample of step (b) includes the expression of the protein of Apolipoprotein A1 from the biological sample. Measuring the level; And measuring the expression level of the protein of Matrix metallopeptidase 9 (MMP9) from the biological sample.

In the step (c), the "normal control group" includes a normal group without bladder cancer or a group that does not develop or recover from bladder cancer. According to the present invention, when the protein expression level of soluble FAS, apolipoprotein A1, and matrix metallopeptidase 9 (MMP9) is high compared to a normal control group, it can be classified as a group of patients with bladder cancer disease.

According to the present invention, the present invention improves the accuracy of the diagnosis and prognosis of bladder cancer through multiple diagnosis of two or three combinations of soluble FAS, apolipoprotein A1 (A1), and matrix metallopeptidase 9 (MMP9), resulting in high accuracy. Can be predicted.

In addition, the prior art uses an invasive cystoscopy and a biomarker in blood for the diagnosis of bladder cancer, but the present invention can provide a method of non-invasively testing a urine sample.

In particular, it is possible to provide a urine biomarker suitable for POCT (on-site diagnosis) or home health care (self-diagnosis) for prognostic management after treatment of bladder cancer with high recurrence.

Hereinafter, the present invention will be described in more detail through examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

<Example 1>

Preoperative urine samples were obtained from 47 patients with bladder cancer, including TURB (Transurethral Resection of Bladder Tumor), radical cystectomy, and 19 kidney donors as a normal control group. sFAS was studied in 20 normal subjects, 35 patients with TURB, and 23 patients with radical cystectomy.

ELISA (enzyme-linked immunosorbent assay) was used to measure MMP9, Apolipoprotein A1, and sFAS in urine. The degree of color development was measured to obtain a standard curve, and then the concentration was measured (see FIGS. 1 to 4).

The concentrations of apolipoprotein A1, MMP9, and sFAS show a large difference between normal subjects and patients, and this is significant. These have implications as candidates for bladder cancer biomarkers. In addition, as in sFAS, there was a significant difference between TURB patients and severely ill patients with radical cystectomy. This indicates that the concentration of sFAS also increases as bladder cancer progresses. The excellence in the diagnosis and prognosis of bladder cancer was analyzed for a panel that combined three biomarkers of apolipoprotein A1, MMP9, and sFAS, which showed significant differences between the normal subjects and patients.

5 is a graph showing the results of performing ROC curve analysis of a combination of two biomarkers of apolipoprotein A1 and MMP9 for sensitivity and specificity.

The ROC curve was confirmed using the concentration values of each of MMP9 and apolipoprotein A1 selected as candidate bladder cancer biomarkers as one panel. The ROC curve expresses how sensitivity and specificity have a relationship with each other on a two-dimensional plane. The larger the AUC (area under curve) value corresponding to the area under the ROC curve, the better the diagnosis method. When the cut off value on the curve was set to 0.66, the most appropriate sensitivity (84%) and specificity (93%) were shown, and the AUC was 0.94.

6 is a graph showing the results of performing ROC curve analysis of a combination of two biomarkers of apolipoprotein A1 and soluble FAS for sensitivity and specificity.

The ROC curve was confirmed by using the concentration values of each of the apolipoprotein A1 and soluble FAS selected as candidate bladder cancer biomarkers as one panel. When the cut off value was set to 0.58, sensitivity (91%) and specificity (93%) were shown, and the AUC was 0.96.

7 is a graph showing the results of performing ROC curve analysis of the two biomarkers of MMP9 and soluble FAS for sensitivity and specificity.

The ROC curve was confirmed using the concentration values of MMP9 and soluble FAS selected as candidate bladder cancer biomarkers as one panel. When the cut off value was set to 0.59, sensitivity (87%) and specificity (93%) were shown, and the AUC was 0.96.

8 is a graph showing the results of performing ROC curve analysis of three biomarkers of apolipoprotein A1, MMP9 and soluble FAS for sensitivity and specificity.

The ROC curve was confirmed by using the concentration values of MMP9, apolipoprotein A1 and soluble FAS selected as candidate bladder cancer biomarkers as one panel. When the cut off value on the curve was set to 0.549, the most appropriate sensitivity (87.5%) and specificity (93.3%) were shown, and the AUC was 0.96.

The selection and application of significant diagnostic markers determines the reliability of the diagnostic results. A significant diagnostic marker means a marker with high reliability so that the result obtained by diagnosis is accurate and thus has high validity and consistent results even in repeated measurements. The combination of two or three types of apolipoprotein A1, MMP9, and sFAS of the present invention is a highly reliable marker combination for bladder cancer diagnosis and prognosis because the difference in expression level is very large compared to the control group.

Meanwhile, the above detailed description should not be construed as restrictive in all respects and should be considered as illustrative. The scope of the present invention should be determined by reasonable interpretation of the appended claims, and all changes within the equivalent scope of the present invention are included in the scope of the present invention.

Claims (12)

An agent for measuring the expression level of a protein of soluble FAS; And
An agent for measuring the expression level of a protein of apolipoprotein A1 or MMP9 (Matrix metallopeptidase 9);
A biomarker composition for diagnosing bladder cancer or analyzing prognosis comprising as an active ingredient.
An agent for measuring the expression level of a protein of soluble FAS;
An agent for measuring the expression level of the protein of Apolipoprotein A1; And
An agent measuring the expression level of the protein of MMP9 (Matrix metallopeptidase 9);
A biomarker composition for diagnosing bladder cancer or analyzing prognosis comprising as an active ingredient.
The method according to claim 1 or 2,
The agent for measuring the expression level of the protein is any one selected from the group comprising antibodies, aptamers, antagonists, and combinations thereof, a biomarker composition for diagnosis or prognosis of bladder cancer.
The method according to claim 1 or 2,
The protein is derived from one or more biological samples selected from the group consisting of tissues, cells, whole blood, serum, plasma, saliva, sputum, and urine obtained from mammals, a biomarker composition for diagnosis or prognosis of bladder cancer.
The method according to claim 1 or 2,
The bladder cancer diagnosis is to diagnose, including the progression and recurrence (Recurrence) of the bladder cancer, bladder cancer diagnosis or prognostic biomarker composition for analysis.
A kit for diagnosing bladder cancer or analyzing prognosis, comprising the composition according to claim 1 or 2.
The method of claim 6,
The kit is a group consisting of a microarray, an aptamer chip kit, an ELISA (enzyme linked immunosorbent assay) kit, a blotting kit, an immunoprecipitation kit, an immunofluorescence test kit, a protein chip kit, and combinations thereof. Kit for diagnosis or prognosis analysis of bladder cancer, characterized in that selected from.
(a) measuring the expression level of the protein of soluble FAS from the biological sample;
(b) measuring the expression level of the protein of apolipoprotein A1 or Matrix metallopeptidase 9 (MMP9) from the biological sample; And
(c) When the expression level of soluble FAS and apolipoprotein A1 (A1) protein is high or the expression level of soluble FAS and MMP9 (Matrix metallopeptidase 9) protein is high compared to the normal control A method of providing information necessary for diagnosis or prognosis analysis of bladder cancer, including.
The method of claim 8,
The step of measuring the expression level of the protein of the (b) apolipoprotein A1 or MMP9 (Matrix metallopeptidase 9) from the biological sample,
Measuring the expression level of the protein of Apolipoprotein A1 from the biological sample; And
Measuring the expression level of the protein of MMP9 (Matrix metallopeptidase 9) from the biological sample;
That includes, a method for providing information necessary for diagnosis or prognosis analysis of bladder cancer.
The method of claim 8,
The expression level of the protein is measured using any one selected from the group including antibodies, aptamers, antagonists, and combinations thereof, a method of providing information necessary for bladder cancer diagnosis or prognosis analysis.
The method of claim 8,
The level measurement, immunoassay, ligand binding assay, MALDI-TOF (Matrix Desorption/Ionization Time of Flight Mass Spectrometry) analysis, SELDI-TOF (Sulface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry) analysis, radioimmunoassay , Radiation immunodiffusion method, Okteroni immunodiffusion method, rocket immunoelectrophoresis, complement fixation method, 2D electrophoresis analysis, liquid chromatography-Mass Spectrometry (LC-MS), LC-MS/MS (liquid chromatography-Mass Spectrometry/Mass Spectrometry), and ELISA (enzyme linked immunosorbent assay) is to use any one method selected from the group consisting of, a method of providing information necessary for bladder cancer diagnosis or prognosis analysis.
The method of claim 8,
The biological sample is selected from the group consisting of tissues, cells, whole blood, serum, plasma, saliva, sputum and urine obtained from mammals,
The bladder cancer diagnosis is to diagnose including the progression and recurrence of the bladder cancer, the method of providing information necessary for bladder cancer diagnosis or prognosis analysis.

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