Application of SNAI1 expression in glioma diagnosis

Abstract

The invention discloses application of SNAI1 expression in glioma diagnosis, and relates to the field of medicine. The application is the application of the SNAI1 gene or the encoded protein thereof as a biomarker in preparation of a product for glioma diagnosis. Wherein the diagnosis comprises the step of judging whether a subject suffers from glioma or evaluating the malignant degree of glioma; when it is detected that the mRNA expression level of the SNAI1 gene or the expression level of the SNAI1 protein in the sample of the subject is higher than a normal control level, it is indicated that the subject suffers from the glioma or the malignant degree of the glioma is high. Analysis of a plurality of independent databases such as TCGA, GEPIA and GEO proves that the mRNA and protein expression levels of SNAI1 in glioma tissues (especially glioblastoma) are obviously higher than those in non-tumor tissues and low-level astrocytoma, and the expression levels are in positive correlation with tumor pathological grading.

Description

Technical Field

[0001] This invention relates to the medical field, and more particularly to the application of SNAI1 expression in the diagnosis of glioma. Background Technology

[0002] Gliomas are the most common primary malignant tumors of the central nervous system, characterized by high invasiveness, high recurrence rate, and poor prognosis. Currently, the diagnosis of gliomas mainly relies on medical imaging examinations and postoperative pathological analysis. However, imaging examinations are difficult to accurately determine the malignancy and prognosis of the tumor, while pathological analysis is invasive and cannot achieve dynamic monitoring. Therefore, finding molecular markers that can be used for early diagnosis, accurate prognostic assessment, and risk stratification of gliomas is of great significance for improving the clinical management of patients.

[0003] Currently, although some known molecular markers associated with gliomas exist (such as IDH mutations and combined 1p / 19q deletions), more sensitive and specific markers are still needed to supplement the existing diagnostic system, especially in non-invasive diagnosis, prognostic prediction, and the development of potential therapeutic targets. SNAI1 (Snail family transcriptional repressor 1) is a key regulator in the epithelial-mesenchymal transition (EMT) process, but its specific clinical value in gliomas, particularly as an independent diagnostic and prognostic marker, has not yet been clearly defined.

[0004] Therefore, this invention proposes an application of SNAI1 expression in the diagnosis of glioma. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by proposing an application of SNAI1 expression in the diagnosis of glioma.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: An application of SNAI1 expression in glioma diagnosis, wherein the application is the use of the SNAI1 gene or its encoded protein as a biomarker in the preparation of products for glioma diagnosis; wherein the diagnosis includes determining whether a subject has glioma or assessing the malignancy of glioma; when the mRNA expression level of the SNAI1 gene or the expression level of the SNAI1 protein in the subject's sample is detected to be higher than the normal control level, it indicates that the subject has glioma or that the glioma is highly malignant.

[0007] Preferably, the application is as follows: the SNAI1 gene or its encoded protein is used as a biomarker in the preparation of a product for prognostic assessment of glioma; wherein, the prognostic assessment includes predicting the overall survival or progression-free survival of glioma patients; when the mRNA expression level of the SNAI1 gene or the expression level of the SNAI1 protein in the patient's tumor sample is detected to be higher than a preset threshold, it indicates that the patient has a poor prognosis.

[0008] Preferably, SNAI1 is used as an independent risk factor in constructing a prognostic assessment model for gliomas; wherein, an independent risk factor means that the prognostic value of SNAI1 does not depend on other clinical variables such as patient age, sex, race and pathological grade, and is determined by univariate and multivariate Cox regression analysis.

[0009] Preferably, the prognostic assessment further quantifies the patient's survival probability by combining the SNAI1 expression level with one or more clinical variables such as the patient's age, sex, race, and pathological grade, and inputting them into a pre-established predictive model or nomograph to calculate the patient's 1-year, 3-year, or 5-year survival probability.

[0010] Preferably, the glioma includes glioblastoma; the expression level of SNAI1 is positively correlated with the pathological grade of the glioma, that is, the expression level is highest in glioblastoma.

[0011] A kit comprising reagents for specifically detecting the mRNA expression level of the SNAI1 gene or the SNAI1 protein expression level; the reagents include specific primers and probes for the SNAI1 gene, or specific antibodies for the SNAI1 protein; the kit also includes instructions for use, indicating how to determine the diagnosis or prognosis of glioma based on the test results.

[0012] An application of SNAI1 expression in the diagnosis of glioma: A diagnostic method for glioma includes the following steps: Obtain biological samples from the subjects; The expression levels of SNAI1 gene mRNA or SNAI1 protein in the sample were detected. The detected expression levels were compared with those of normal controls; If the expression level is significantly higher than that of the normal control, the subject is judged to have glioma or a high degree of malignancy in the glioma.

[0013] A prognostic assessment method for the application of SNAI1 expression in the diagnosis of glioma includes the following steps: Obtain tumor tissue samples from glioma patients; The expression levels of SNAI1 gene mRNA or SNAI1 protein in the sample were detected. Based on the test results, patients were divided into a high-expression group or a low-expression group of SNAI1. Patients classified as having high SNAI1 expression were predicted to have shorter overall survival and progression-free survival, and a poorer prognosis.

[0014] A method for screening or evaluating anti-glioma drugs, targeting SNAI1; comprising: The candidate substance was administered to the test system, and it was observed whether the candidate substance could downregulate the expression level of SNAI1 or inhibit its biological function. If the candidate substance can effectively downregulate the expression or function of SNAI1, it indicates that the candidate substance has the potential to treat glioma.

[0015] The beneficial effects of this invention are as follows: Clear diagnostic value: Analysis of multiple independent databases such as TCGA, GEPIA, and GEO confirmed that the mRNA and protein expression levels of SNAI1 in glioma tissues (especially glioblastoma) were significantly higher than those in non-tumor tissues and low-grade astrocytomas, and the expression level was positively correlated with the tumor pathological grade.

[0016] Strong prognostic predictive ability: Survival analysis showed that glioma patients with high SNAI1 expression had significantly shorter overall survival and progression-free survival. Univariate and multivariate Cox regression analyses confirmed that high SNAI1 expression was a prognostic risk factor independent of other clinical factors such as age and pathological stage, suggesting its reliability as a prognostic biomarker.

[0017] With diverse applications, this invention not only provides a diagnostic and prognostic method based on SNAI1 expression levels, but also constructs a nomogram that includes clinical variables such as SNAI1 expression levels, age, gender, race, and pathological grade. This nomogram can quantify and predict patients' 1-year, 3-year, and 5-year survival probabilities, providing clinicians with a more intuitive and personalized prognostic assessment tool. Attached Figure Description

[0018] Figure 1 This diagram illustrates the expression of SNAI1 in gliomas and its positive correlation with grading, as described in the present invention. Figure 1 A: Pan-cancer analysis diagram of SNAI1 expression levels in various human tumor tissues and normal tissues; Figure 1 B: Comparison of SNAI1 expression levels between glioblastoma tissue and non-tumor brain tissue; Figure 1C: Validation diagram of SNAI1 mRNA expression level in glioblastoma; Figure 1 D and Figure 1 E: Validation diagram of SNAI1 mRNA expression levels in different grades of gliomas and non-tumor control groups; Figure 1 F: Immunohistochemical results of SNAI1 protein expression levels in normal tissues, low-grade astrocytomas, and glioblastomas; Figure 2 This is a schematic diagram illustrating the prognostic value of SNAI1 and the construction of a nomogram according to the present invention, wherein: Figure 2 A: ROC curve of SNAI1 expression level in relation to the diagnostic value of glioma; Figure 2 B: Kaplan-Meier curves of overall survival and progression-free survival in glioma patients based on SNAI1 expression levels; Figure 2 C: Table of univariate and multivariate Cox regression analysis results for assessing whether SNAI1 is an independent prognostic risk factor; Figure 2 D: A nomogram that integrates clinical variables such as SNAI1 expression level, age, sex, race, and pathological grade to predict the 1-year, 3-year, and 5-year survival probability of patients. Figure 2 E: Yes Figure 2 D shows the calibration curve used to verify the accuracy of the nomograph prediction. Figure 3 Spearman correlation analysis plot of SNAI1 scores with epithelial-mesenchymal transition-related signaling pathways. Detailed Implementation

[0019] The technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0020] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "setting" should be interpreted broadly. For example, they can refer to a fixed connection or setting, a detachable connection or setting, or an integral connection or setting. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0021] Example 1: SNAI1 overexpression was observed in glioma patients and was positively correlated with cancer grade. To determine the expression pattern of SNAI1 in tumor and non-tumor lung tissues, we analyzed the expression level of SNAI1 in different tumors and normal tissues using the TCGA database. SNAI1 expression was significantly enhanced in tumors including cholangiocarcinoma (CHOL), colorectal cancer (COAD), esophageal cancer (ESCA), glioblastoma (GBM), head and neck squamous cell carcinoma (HNSC), clear cell renal carcinoma (KIRC), rectal adenocarcinoma (READ), cutaneous melanoma (SKCM), and gastric adenocarcinoma (STAD). Furthermore, SNAI1 expression was lower in bladder urothelial carcinoma (BLCA), cervical squamous cell carcinoma and cervical endometrial carcinoma (CESC), renal chromophobe carcinoma (KICH), renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), pheochromocytoma and paraganglioma (PCPG), thymic carcinoma (THYM), and endometrial carcinoma (UCEC). Figure 1 A). Furthermore, in the GEPIA database, the mean expression level of SNAI1 in glioblastoma tissues was significantly higher than in non-tumor tissues (A). Figure 1 B). Similar results were obtained from the GEO database using the GSE86574 dataset, indicating that SNAI1 has high mRNA expression levels in glioblastoma. Figure 1 C). Subsequent validation using the TCGA, GSCA693, and GSCA301 datasets further demonstrated that SNAI1 mRNA levels in glioblastoma patients were significantly higher than in astrocytoma cases and non-tumor controls, indicating a positive correlation between SNAI1 expression and histopathological tumor grade progression. Figure 1 D, 1E). Furthermore, the THPA database indicates that SNAI1 antibody is expressed at low levels in normal tissues, increases in low-grade astrocytomas, and reaches its highest expression in glioblastomas. Figure 1 F). In summary, these findings indicate that SNAI1 expression is increased at both the mRNA and protein levels in glioma tissues, and a stronger SNAI1 signal is observed in most glioblastoma tissues, suggesting a positive correlation between SNAI1 expression and cancer grade.

[0022] 2. Survival Analysis: In the TCGA database, SNAI1 expression levels in each glioma patient were assigned to high-expression and low-expression groups based on the median SNAI1 expression level. Kaplan-Meier curves were then plotted using TCGA data, revealing that elevated SNAI1 levels were associated with poorer overall survival (OS). Finally, ROC curve analysis was used to assess the reliability of the diagnostic value model of SNAI1 expression levels for gliomas (1 year, AUC=0.788; 3 years, AUC=0.786; 5 years, AUC=0.746). Figure 2 A). Further analysis using the GEPIA database showed that the high expression of SNAI1 significantly reduced overall survival and progression-free survival. Figure 2 B).

[0023] SNAI1 is an independent risk factor: Furthermore, univariate and multivariate Cox regression analyses were used to assess the relationship between SNAI1 and clinical characteristics of glioma. The results showed that high SNAI1 expression was significantly associated with patient age and pathological stage, suggesting that SNAI1 is an independent risk factor. Figure 2 C).

[0024] Diagnostic and predictive value of SNAI1 expression in gliomas: To examine the predictive value of SNAI1 expression levels in gliomas, we constructed a nomogram based on the SNAI1 expression profile in the TCGA database. Clinical variables were selected in conjunction with multivariate Cox analysis results and frequent clinical variables age and sex to construct nomograms predicting 1-year, 3-year, and 5-year survival probabilities. Figure 2 D). Calibrate the nomograph using the calibration curve ( Figure 2 E).

[0025] 3. SNAI1 was positively correlated with EMT pathway scores. The relationship between SNAI1 and pathway scores was studied using Spearman correlation analysis. It can be seen that SNAI1 is positively correlated with EMT-related signaling pathways. Figure 3 EMT has been studied in particular in cancer, where it can be locally and time-dependently activated to produce tumor cells with enhanced invasive mesenchymal properties.

[0026] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. An application of SNAI1 expression in the diagnosis of glioma, characterized in that, The application is the use of the SNAI1 gene or its encoded protein as a biomarker in the preparation of products for glioma diagnosis; wherein the diagnosis includes determining whether a subject has glioma or assessing the malignancy of glioma; when the mRNA expression level of the SNAI1 gene or the expression level of the SNAI1 protein in the subject's sample is detected to be higher than the normal control level, it indicates that the subject has glioma or that the glioma is highly malignant.

2. The application of SNAI1 expression in the diagnosis of glioma according to claim 1, characterized in that, The application is the use of the SNAI1 gene or its encoded protein as a biomarker in the preparation of products for prognostic assessment of gliomas; wherein, the prognostic assessment includes predicting the overall survival or progression-free survival of glioma patients; when the mRNA expression level of the SNAI1 gene or the expression level of the SNAI1 protein in the patient's tumor sample is detected to be higher than a preset threshold, it indicates that the patient has a poor prognosis.

3. The application of SNAI1 expression in the diagnosis of glioma according to claim 1, characterized in that, The application of SNAI1 as an independent risk factor in constructing a prognostic assessment model for gliomas; whereby an independent risk factor means that the prognostic value of SNAI1 does not depend on other clinical variables such as patient age, sex, race, and pathological grade, and is determined through univariate and multivariate Cox regression analysis.

4. The application of SNAI1 expression in the diagnosis of glioma according to claim 2, characterized in that, Prognostic assessment further quantifies the patient's survival probability by combining SNAI1 expression levels with one or more clinical variables, such as the patient's age, sex, race, and pathological grade, and inputting them into a pre-established predictive model or nomograph to calculate the patient's 1-year, 3-year, or 5-year survival probability.

5. The application of SNAI1 expression in the diagnosis of glioma according to any one of claims 1-4, characterized in that, Gliomas include glioblastomas; the expression level of SNAI1 is positively correlated with the pathological grade of gliomas, that is, the expression level is highest in glioblastomas.

6. A kit for the application of SNAI1 expression in the diagnosis of glioma according to claim 1 or 2, characterized in that, The kit contains reagents for specifically detecting the mRNA expression level of the SNAI1 gene or the SNAI1 protein expression level; the reagents include specific primers and probes for the SNAI1 gene, or specific antibodies for the SNAI1 protein; the kit also includes instructions for use, which indicate how to determine the diagnosis or prognosis of glioma based on the test results.

7. A diagnostic method for gliomas based on the application of SNAI1 expression in glioma diagnosis according to claim 1, characterized in that, Includes the following steps: Obtain biological samples from the subjects; The expression levels of SNAI1 gene mRNA or SNAI1 protein in the sample were detected. The detected expression levels were compared with those of normal controls; If the expression level is significantly higher than that of the normal control, the subject is judged to have glioma or a high degree of malignancy in the glioma.

8. The prognostic assessment method for SNAI1 expression in glioma diagnosis according to claim 2, characterized in that, Includes the following steps: Obtain tumor tissue samples from glioma patients; The expression levels of SNAI1 gene mRNA or SNAI1 protein in the sample were detected. Based on the test results, patients were divided into a high-expression group or a low-expression group of SNAI1. Patients classified as having high SNAI1 expression were predicted to have shorter overall survival and progression-free survival, and a poorer prognosis.

9. A method for screening or evaluating anti-glioma drugs, characterized in that, It targets SNAI1; including: The candidate substance was administered to the test system, and it was observed whether the candidate substance could downregulate the expression level of SNAI1 or inhibit its biological function. If the candidate substance can effectively downregulate the expression or function of SNAI1, it indicates that the candidate substance has the potential to treat glioma.

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