Application of CERS5 as a biomarker in the preparation of a detection agent for gastric cancer prognosis

Abstract

The present invention discloses the application of CERS5 as a biomarker in the preparation of a detection agent for gastric cancer prognosis, belonging to the field of tumor molecular biology. The detection agent is used for detecting the level of CERS5 in samples of gastric cancer patients in the Asian population. The expression level of CerS5 is an independent influencing factor for the poor prognosis of gastric cancer in the Asian population. The present invention also provides the application of CERS5 as a biomarker in constructing a model for evaluating the prognosis of gastric cancer in gastric cancer patients, where the gastric cancer patients are gastric cancer patients in the Asian population. A tissue microarray is constructed from samples of gastric cancer patients in the Asian population; the expression of CERS5 in the tissue microarray is detected by immunohistochemistry; the H scoring system is used to evaluate the expression intensity of CERS5. If the CERS5 level in the sample of a gastric cancer patient > the critical value, it indicates a poor prognosis for the gastric cancer patient; if the CERS5 level in the sample of a gastric cancer patient ≤ the critical value, it indicates a good prognosis for the gastric cancer patient.

Description

Technical Field

[0001] The present invention belongs to the field of tumor molecular biology, and particularly relates to the application of CERS5 as a biomarker in the preparation of a detection agent for gastric cancer prognosis. Background Art

[0002] Gastric cancer is one of the most common malignant tumors globally, with the incidence and mortality rates ranking 5th and 4th respectively. According to statistics, there were over 1 million newly diagnosed gastric cancer patients in 2020. The overall prognosis of gastric cancer is poor, with a 5-year survival rate of only 35.1%. Surgical resection remains the main method for treating gastric malignancies. In recent years, with the development of treatment techniques such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy, the treatment plan for gastric cancer has gradually become comprehensive. However, due to the toxic side effects and drug resistance of drugs, the overall treatment effect of gastric cancer is still not satisfactory. Currently, the early screening and diagnosis methods for gastric cancer mainly rely on imaging examinations, tumor markers, endoscopic examinations, and tissue biopsies, etc. Pathological diagnosis obtained by endoscopic biopsy is the gold standard for current gastric cancer diagnosis. However, due to the invasiveness of endoscopic procedures, early screening and diagnosis of gastric cancer have not been popularized. Therefore, it is particularly important to find early diagnosis or treatment targets for gastric cancer.

[0003] Ceramide synthases (CERSs) are essential membrane proteins in the endoplasmic reticulum. So far, six types of CERSs (CERS1 - CERS6), including CERS5, have been discovered in mammals. CERSs are involved in the de novo synthesis pathway and salvage pathway of ceramide (CERs). At the same time, bioactive sphingomyelin ceramide (CERs) is not only a structural component of biological membranes but also a signal molecule that induces cell death and tumor suppression. Different CERSs have different fatty acyl-CoA chain lengths, which means that CERSs may be involved in the regulation of different tissues and affect their metabolism. Some studies have confirmed that changes in CERSs levels are closely related to the apoptosis and malignant progression of tumor cells. However, the function of CERS5 in gastric cancer remains to be revealed. Summary of the Invention

[0004] One object of the present invention is to provide the application of a biomarker related to the prognosis of gastric cancer in Asian populations. The biomarker is CERS5, which can be used as a biomarker to construct a model for evaluating the prognosis of gastric cancer in gastric cancer patients, and can also be used as a biomarker to prepare a detection agent for gastric cancer prognosis.

[0005] The technical solution adopted by the present invention to achieve the above object is as follows:

[0006] The application of CERS5 as a biomarker in constructing a model for evaluating the prognosis of gastric cancer in gastric cancer patients, where the gastric cancer patients are gastric cancer patients in Asian populations, and the model is constructed by the following method,

[0007] 1) Construct a tissue microarray from gastric cancer patient samples of the Asian population;

[0008] 2) Detect the expression of CERS5 in the tissue microarray by immunohistochemistry;

[0009] 3) Use the H scoring system to evaluate the expression intensity of CERS5. Among them,

[0010] - If the CERS5 level in the gastric cancer patient sample > the critical value, this indicates a poor prognosis for the gastric cancer patient;

[0011] - If the CERS5 level in the gastric cancer patient sample ≤ the critical value, this indicates a good prognosis for the gastric cancer patient.

[0012] CERS5 is highly expressed in the gastric cancer tissue and / or metastatic lymph node tissue of gastric cancer patients. Its expression level is an independent influencing factor for the poor prognosis of gastric cancer in the Asian population. The higher the expression level of CERS5 in the gastric cancer tissue and / or metastatic lymph node tissue of Asian gastric cancer patients, the worse the prognosis of gastric cancer patients; the lower the expression level of CERS5 in the gastric cancer patient samples of the Asian population, the better the prognosis of gastric cancer patients. In addition, an increase in CerS5 level was significantly associated with poor prognosis in gastric cancer patients collected from ACRG, but not with TCGA, indicating that CerS5 is a prognostic marker for gastric cancer in the Asian population.

[0013] Preferably, the gastric cancer patient is a primary gastric cancer patient.

[0014] Preferably, the sample includes gastric cancer tissue and / or metastatic lymph node tissue.

[0015] Preferably, the gastric cancer patient sample is a formalin-fixed and / or paraffin-embedded gastric cancer patient sample.

[0016] Preferably, the formula of the H scoring system is as follows: H score = (∑IS × AP), where IS represents the staining intensity, no staining is 0 points, weak staining is 1 point, moderate staining is 2 points; AP represents the percentage of positively stained cells, 0% is 0 points, 1%-25% is 1 point, 26%-50% is 2 points, 51%-75% is 3 points, 76%-100% is 4 points.

[0017] Preferably, the critical value = 4 points.

[0018] The present invention also provides the application of CERS5 as a prognostic marker for gastric cancer patients. The gastric cancer patients are Asian gastric cancer patients, and CERS5 is detected in the gastric cancer patient samples; the higher the expression level of CERS5 in the gastric cancer patient samples, the worse the prognosis of gastric cancer patients; the lower the expression level of CERS5 in the gastric cancer patient samples, the better the prognosis of gastric cancer patients.

[0019] Preferably, the gastric cancer patients are primary gastric cancer patients.

[0020] Preferably, the gastric cancer patient samples include gastric cancer tissues and / or metastatic lymph node tissues.

[0021] Preferably, the gastric cancer patient samples are formalin-fixed and / or paraffin-embedded gastric cancer patient samples.

[0022] Preferably, after the gastric cancer patient samples are stained by immunohistochemistry, the CERS5 expression intensity is evaluated by using the immunohistochemical H scoring system.

[0023] More preferably, the formula of the H scoring system is as follows: H score = (∑IS × AP), where IS represents the staining intensity, 0 points for no staining, 1 point for weak staining, and 2 points for moderate staining. AP represents the percentage of positively stained cells, 0 points for 0%, 1 point for 1% - 25%, 2 points for 26% - 50%, 3 points for 51% - 75%, and 4 points for 76% - 100%.

[0024] Further preferably, gastric cancer patients with H score ≤ the critical value are in the CERS5 low-expression group, and gastric cancer patients with H score > the critical value are in the CERS5 high-expression group. Even more preferably, the critical value = 4 points.

[0025] Even more preferably, the 5-year overall survival rate of the CERS5 high-expression group in the gastric cancer tissues of gastric cancer patients is 32.8%, and the 5-year overall survival rate of the CERS5 low-expression group in the gastric cancer tissues of gastric cancer patients is 52.8%.

[0026] The present invention also provides the application of CERS5 as a biomarker in the preparation of a gastric cancer prognosis detection preparation, and the detection preparation is used for detecting the CERS5 level in gastric cancer patient samples of the Asian population.

[0027] Preferably, the detection preparation includes a CERS5 antibody.

[0028] The present invention also provides a gastric cancer prognosis detection preparation, including a reagent for detecting the CERS5 expression level in gastric cancer patient samples.

[0029] Preferably, the gastric cancer patients are gastric cancer patients of the Asian population, and the gastric cancer patient samples are gastric cancer tissues and / or metastatic lymph node tissues.

[0030] Preferably, the reagent is a CERS5 antibody.

[0031] The present invention also provides a kit for gastric cancer prognosis detection, including the reagent for detecting the CERS5 level in gastric cancer patient samples as described above.

[0032] Preferably, the measured CERS5 level is the CERS5 protein level.

[0033] Preferably, the CERS5 protein level is determined by immunohistochemical staining, ELISA or Western blotting.

[0034] The present invention also provides the application of CERS5 in the auxiliary diagnosis of gastric cancer. The expression level of CERS5 is positively correlated with the value of CA50. The abnormal rate of glycoprotein antigen CA50 in gastric cancer patients with high expression of CERS5 in gastric cancer tissues is 20.4%, and the abnormal rate of CA50 in gastric cancer patients with low expression of CERS5 in gastric cancer tissues is only 6.3%. This means that CERS5 has certain value in the auxiliary diagnosis of gastric cancer.

[0035] Since the present invention uses CERS5 as a prognostic marker for gastric cancer, it has the following beneficial effects: CERS5 is highly expressed in gastric cancer tissues and / or metastatic lymph node tissues of gastric cancer patients, and its expression level is an independent influencing factor for the poor prognosis of gastric cancer in the Asian population. The higher the expression level of CERS5 in gastric cancer tissues and / or metastatic lymph node tissues of Asian gastric cancer patients, the worse the prognosis of gastric cancer patients; the lower the expression level of CERS5 in the samples of Asian gastric cancer patients, the better the prognosis of gastric cancer patients. Among them, the 5-year overall survival rate of the high-expression group of CERS5 in gastric cancer tissues of Asian gastric cancer patients is 32.8%, and the 5-year overall survival rate of the low-expression group of CERS5 in gastric cancer tissues of Asian gastric cancer patients is 52.8%. In addition, the increase in CerS5 level is significantly correlated with the poor prognosis of gastric cancer patients collected from ACRG, but not related to TCGA, which indicates that CerS5 is a prognostic marker for gastric cancer in the Asian population. Therefore, the present invention provides the application of a marker CERS5 related to the prognosis of gastric cancer in the Asian population, which can be used as a marker to construct a model for evaluating the prognosis of gastric cancer in gastric cancer patients, and can also be used as a marker to prepare a detection preparation for gastric cancer prognosis. Description of the Drawings

[0036] Figure 1 Immunohistochemical staining of CERS5 in tumor tissues, adjacent tissues and metastatic lymph node tissues of gastric cancer patients;

[0037] Figure 2 Differential expression of CERS5 in gastric cancer, a is the differential expression of CERS5 in tumor tissues and adjacent tissues based on 150 clinical samples, b is the differential expression of CERS5 in tumor tissues and normal tissues based on TCGA, c is the differential expression of CERS5 in tumor tissues and normal tissues based on ACRG, d is the differential expression of CERS5 in tumor tissues and metastatic lymph node tissues based on 99 clinical specimens;

[0038] Figure 3For the correlation between CERS5 and the prognosis of gastric cancer patients, a is the overall survival rate of gastric cancer patients with low CERS5 expression and high CERS5 expression, b is the survival probability of gastric cancer patients with different CERS5 levels from the TCGA database, and c is the survival probability of gastric cancer patients with different CERS5 levels from the ACRG database. Detailed implementation manner

[0039] To make the objectives, technical solutions, and advantages of the present invention more clear and understandable, the present invention will be further described in detail below with reference to specific embodiments and the accompanying drawings.

[0040] The experimental methods in the following embodiments are all conventional methods unless otherwise specified. The materials, reagents, etc. used in the following embodiments can all be obtained from commercial channels unless otherwise specified.

[0041] Example 1:

[0042] 1. Materials and methods

[0043] 1.1. Patients

[0044] A total of 150 patients who underwent radical gastrectomy and were admitted to the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) between January 2013 and December 2017 were collected. All patients were of Asian ethnicity. The inclusion criteria were as follows: (1) The postoperative pathology was clearly diagnosed as gastric cancer; (2) The patient's medical record data was relatively complete; (3) Anti-tumor comprehensive treatments such as radiotherapy, chemotherapy, targeted therapy, or immunotherapy were not performed before surgery; (4) There were complete survival follow-up data. The exclusion criteria were as follows: (1) Patients with other types of malignant tumors; (2) Patients metastasized from other malignant tumors. The medical record data of this batch of patients were retrospectively collected, including demographic characteristics and clinicopathological characteristics, and the overall survival time was obtained through telephone follow-up. The last follow-up time was August 2021. The overall survival (OS) was defined as the duration from the initial surgery to death or the last follow-up.

[0045] 1.2. Immunohistochemical staining method

[0046] The tissue samples were fixed with formalin and embedded in paraffin to prepare tissue specimens. Representative gastric cancer tissue specimens, adjacent tissue specimens, and metastatic lymph node specimens were collected to construct a tissue microarray and stained by immunohistochemistry. The sections were incubated at 56 - 60 °C for 15 minutes, and the xylene was changed twice. The sections were rehydrated with ethanol, 90% ethanol, and 80% ethanol, then rinsed in gently flowing tap water and washed with 1×PBS. Subsequently, the sections were incubated in water in a microwave oven three times for 5 minutes each time, slowly cooled to room temperature, incubated with 3% hydrogen peroxide for 5 minutes, and then the primary antibody (anti-CERS5 1:500) was added and incubated overnight at 4 °C. The sections were washed with 1×PBS for 5 minutes × 3 times; then the secondary antibody (goat anti-rabbit IgG H&L, 1:1000) was added to the tissue microarray and incubated for 30 minutes, and the sections were washed with 1×PBS for 5 minutes × 3 times; then the IHC kit (Abcam, ab64261) for rabbit-specific HRP / DAB (ABC) was used to detect DAB, and the cell nuclei were stained with hematoxylin. Finally, the tissue microarray was dehydrated and sealed with neutral gel.

[0047] 1.3. Interpretation of staining results

[0048] The expression intensity of CERS5 was evaluated using the H-score system. The formula of the H-score system is as follows: H-score = (∑IS × AP), where IS represents the staining intensity, 0 points for no staining, 1 point for weak staining, and 2 points for moderate staining. AP represents the percentage of positively stained cells, 0 points for 0%, 1 point for 1% - 25%, 2 points for 26% - 50%, 3 points for 51% - 75%, and 4 points for 76% - 100%. The median H-score of CERS5 was 4 points, which was set as the cut-off value, and the patients with different CERS5 levels were divided into the high-expression group and the low-expression group.

[0049] 1.4. Public tumor databases

[0050] The RNA-seq data of gastric cancer patients were downloaded from the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) (21) databases, with 405 cases from TCGA and 246 cases from ACRG. The CERS5 levels in gastric cancer tissues and adjacent tissues were compared. According to the corresponding clinicopathological data, the Kaplan-Meier method was used to determine the correlation between CERS5 level and the survival time of gastric cancer patients.

[0051] 1.5. Data analysis

[0052] Statistical analysis was performed using SPSS 25.0 software. Chi-square test, corrected chi-square test, and Fisher's exact test were used to analyze the correlation between CERS5 expression level and clinicopathological features. The Kaplan-Meier method was used to plot the survival curve, and univariate and multivariate Cox regression analyses were used to analyze the independent factors affecting the prognosis of gastric cancer patients. At the same time, the hazard ratio (HR) and 95% confidence interval (CI) were calculated. p < 0.05 represented statistical significance.

[0053] 2. Results

[0054] 2.1. Clinicopathological features

[0055] The median age of the gastric cancer patients included in the study was 61 years, including 106 males (70.7%) and 44 females (29.3%). In terms of the tumor location distribution, distal gastric cancer accounted for the majority, accounting for 61.3%. In terms of the tumor TNM stage, most patients were in stage III, accounting for 78.7% of the total, and the patients in stage II and stage IV accounted for 12.0% and 9.3% respectively. Among the 150 patients, the pathological examination showed that the degree of differentiation was mainly low differentiation and medium-low differentiation, accounting for 44.0% and 34.7% respectively. All the enrolled patients were followed up regularly, and the last follow-up time was in August 2021. During the follow-up period, 81 patients died. More specific clinicopathological data are shown in Table 1.

[0056] Table 1 Clinicopathological features of 150 gastric cancer patients

[0057]

[0058]

[0059] Note: x represents unknown

[0060] 2.2. Expression levels of CERS5 in gastric cancer tissues and adjacent tissues

[0061] Through immunohistochemical staining, it was found that CERS5 was expressed in 118 of the 150 gastric cancer patient tissues, accounting for 78.7%. The number of gastric cancer patients with negative CERS5 expression (0 score) was 32, accounting for 21.3% ( Figure 1 and Table 2). According to the immunohistochemical H score evaluation standard, the median H score of CERS5 was 4 points. Taking H score = 4 points as the cut-off value, we defined the patients with H score ≤ 4 points as the CERS5 low-expression group, and the patients with H score > 4 points as the CERS5 high-expression group. High levels of CERS5 were present in the tumor tissues of 50 / 150 (33.3%) patients, while CERS5 was only present in the adjacent tissues of 24 / 150 (16.0%) patients ( Figure 2a and Table 3). These data indicate that CERS5 is highly expressed in the tumor tissues of gastric cancer patients compared to adjacent tissues. To explore the expression of CERS5 in gastric cancer tissues from different populations, RNA-seq data of CERS5 were extracted from the TCGA database and the ACRG database respectively. In terms of proportion and clinical characteristics, the TCGA database mainly includes European and American populations, while the ACRG database mainly includes Asian populations. 373 tumor tissues and 32 normal tissues were collected from TCGA, and 122 tumor tissues and 123 normal tissues were collected from ACRG. The results show that CERS5 is overexpressed in cancer tissues compared to normal tissues in TCGA and ACRG ( Figure 2 b and 2c), which means that CERS5 is generally upregulated in gastric cancer patients regardless of population.

[0062] To study the role of CERS5 in gastric cancer patients from different populations, we downloaded the RNA-seq data of CERS5 from the TCGA and ACRG databases. In terms of proportion and clinical characteristics, TCGA is mainly based on European populations, while ACRG is mainly based on Asian populations. 373 tumor tissues and 32 normal tissues were collected from TCGA, and 122 tumor tissues and 123 normal tissues were collected from ACRG respectively. The results show that CERS5 is highly expressed in gastric cancer tissues from different populations, and the conclusions of the TCGA database and the ACRG database are consistent ( Figure 2 b and 2c). The above results indicate that CERS5 is generally highly expressed in gastric adenocarcinoma patients, and its expression level has no correlation with race.

[0063] Table 2 Expression levels of CERS5 in tumor tissues

[0064]

[0065] Note: Score ≥ 1 indicates expression; score > 4 indicates high expression

[0066] Table 3 Expression levels of CERS5 in tumor tissues and adjacent tissues

[0067]

[0068] Note: ** represents p <0.001

[0069] 2.3. Expression levels of CERS5 in gastric cancer tissues and metastatic lymph node tissues

[0070] To further analyze the difference in CERS5 expression levels between gastric cancer tissues and metastatic lymph node tissues, paired tissues from the same patients were collected and subjected to IHC staining. It was found that 99 out of 150 gastric cancer patients had perigastric lymph node metastasis, with a metastasis rate of 66.0%. In addition, among the 99 patients with perigastric lymph node metastasis, 29 cases (29.3%) had high CERS5 expression and 70 cases (70.7%) had low CERS5 expression; among the 99 paired gastric cancer tissue samples, 38 cases (38.4%) had high CERS5 expression and 61 cases (61.6%) had low CERS5 expression; however, among the 99 paired adjacent tissue samples, 14 cases (14.1%) had high CERS5 expression and 85 cases (85.9%) had low CERS5 expression (Table 4). The results showed that the expression of CERS5 in metastatic lymph node tissues was significantly higher than that in paired adjacent tissues (p = 0.01), while there was no significant difference in the expression of CERS5 between gastric cancer tissues and metastatic lymph node tissues (p = 0.176). These data indicate that CERS5 is overexpressed in both cancer tissues and metastatic lymph node tissues compared with adjacent tissues of gastric cancer patients ( Figure 2 d).

[0071] Table 4 Expression levels of CERS5 in tumor tissues, adjacent tissues, and metastatic lymph node tissues

[0072]

[0073] Note: * represents p <0.05; ** represents p <0.001

[0074] 2.4. CERS5 expression and clinicopathological features

[0075] To clarify the correlation between CERS5 and clinicopathological features, the collected retrospective clinicopathological data were sorted out, and various statistical methods such as chi-square test, corrected chi-square test, or Fisher's exact test were used for statistical analysis and correlation analysis. As shown in Table 5, when CERS5 was lowly expressed, the main location of gastric cancer patients was distal gastric cancer (66 / 96, 68.8%), and when CERS5 was highly expressed, the main locations of gastric cancer patients were proximal (23 / 54, 42.6%) and distal (26 / 54, 48.1%) gastric cancer. The correlation between CERS5 level and tumor location was statistically significant ( p = 0.045), indicating that CERS5 was involved in the distribution of gastric cancer. In addition, we also found that among gastric cancer patients with high CERS5 expression, the abnormal rate of glycoprotein antigen CA50 was 20.4% (11 / 54), while the abnormal rate of CA50 in patients with low CERS5 expression was only 6.3% (6 / 96) (Table 5, p= 0.011), there was a correlation between CERS5 and the CA50 value in gastric cancer patients (Table 5, p = 0.011). As a non-specific broad-spectrum tumor marker, glycoprotein antigen CA50 is mainly used for the auxiliary diagnosis of pancreatic cancer, colorectal cancer, and gastric cancer. Our study found that the expression level of CERS5 was positively correlated with the CA50 value, which means that CERS5 has certain value in the auxiliary diagnosis of gastric cancer. However, other indicators such as age, gender, smoking history, drinking history, family history, TNM stage, Lauren classification, tumor size, tumor differentiation degree, and common digestive tract tumor markers such as CA125 were not significantly correlated with the expression level of CERS5.

[0076] Table 5 Correlation between CERS5 and clinicopathological features of gastric cancer

[0077]

[0078]

[0079] Note: * represents p < 0.05; x represents unknown

[0080] 2.5. Influence of CERS5 expression on the prognosis of gastric cancer

[0081] To explore the influence of CERS5 level on the prognosis of gastric cancer patients, we regularly followed up 150 gastric cancer patients to obtain survival data, and used the Kaplan-Meier method to draw survival curves to analyze the influence of the CERS5 expression level in gastric cancer tissues on the prognosis of patients. As Figure 3As shown in Figure a, the prognosis of gastric cancer patients in the high CERS5 expression group was significantly worse than that in the low expression group. The 5-year survival rate of the low CERS5 expression group was 52.8%, while that of the high CERS5 expression group was only 32.8%. These results suggest that the expression level of CERS5 is negatively correlated with the prognosis of gastric cancer patients. To verify the correlation between CERS5 and the prognosis of gastric cancer in a larger cohort, we collected samples from 399 gastric cancer patients from TCGA and divided them into two different groups, the high expression group and the low expression group. As shown in Figure 3b, there was no significant correlation between CERS5 level and the prognosis of TCGA gastric cancer patients. Since TCGA is mainly based on European populations, we collected the survival data of gastric cancer patients from ACRG, which is based on Asian populations, to further study the role of CERS5 in different populations. The samples of 300 gastric cancer patients and the corresponding survival data from ACRG (GSE66229, https: / / www.ncbi.nlm.nih.gov / geo) were analyzed by the Kaplan-Meier method. The results showed that patients with high CERS5 expression levels in the GSE66229 dataset had a worse prognosis than those with low CERS5 expression levels, indicating that the expression level of CERS5 was significantly negatively correlated with the prognosis ( Figure 3 c). The above results indicate that the expression level of CERS5 is correlated with the prognosis of gastric cancer patients from Asian populations, but not with the prognosis of gastric cancer from European and American populations.

[0082] To clarify the impact of CERS5 expression level and clinicopathological characteristics on the prognosis of gastric cancer patients, first, univariate Cox regression analysis was used to analyze each factor included in the study (Table 6). The results showed that the expression level of CERS5 (p = 0.023), family history of gastric cancer (p = 0.008), Lauren classification (p = 0.015), N stage (p < 0.001), M stage (p < 0.001), TNM stage (p = 0.001), hemangioma thrombus (p = 0.001), CEA (p = 0.005), and CA125 (p < 0.001) were related factors affecting the prognosis of patients. Next, the indicators with p < 0.1 in the results of univariate Cox regression analysis were included in the multivariate Cox regression analysis. The results showed that these 5 indicators, namely CERS5 expression (p = 0.046), Lauren classification (p = 0.022), N stage (p = 0.010), M stage (p = 0.023), and CA125 (p = 0.001), were independent influencing factors affecting the prognosis of gastric cancer patients (Table 7).

[0083] Table 6 Univariate COX regression analysis of 150 gastric cancer patients

[0084]

[0085] Note: * represents p <0.05; ** represents p <0.001

[0086] Table 7 Multivariate COX regression analysis of 150 gastric cancer patients

[0087]

[0088] Note: * represents p <0.05

[0089] The routine operations in the operation steps of the present invention are well-known to those skilled in the art and will not be elaborated herein.

[0090] The above-described embodiments have described the technical solutions of the present invention in detail. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the present invention. Any modifications, supplements, or substitutions in a similar manner within the principle scope of the present invention should be included within the protection scope of the present invention.

Claims

1. The application of CERS5 as a biomarker in constructing a model for evaluating the prognosis of gastric cancer in gastric cancer patients, wherein the gastric cancer patients are Asian gastric cancer patients, and the model is constructed by the following method: 1) Construct a tissue microarray from samples of Asian gastric cancer patients; 2) Detect the expression of CERS5 in the tissue microarray by immunohistochemistry; 3) Evaluate the expression intensity of CERS5 using the H-scoring system, wherein, - If the CERS5 level in the gastric cancer patient sample > the critical value, this indicates a poor prognosis for the gastric cancer patient; - If the CERS5 level in the gastric cancer patient sample ≤ the critical value, this indicates a good prognosis for the gastric cancer patient.

2. The application according to claim 1, characterized in that: The gastric cancer patients mentioned are primary gastric cancer patients.

3. The application according to claim 1, characterized in that: The samples mentioned include gastric cancer tissues and / or metastatic lymph node tissues.

4. The application according to claim 1, characterized in that: The formula for the H scoring system is as follows: H score = (∑IS × AP), where IS represents the staining intensity, 0 points for no staining, 1 point for weak staining, and 2 points for moderate staining; AP represents the percentage of positively stained cells, 0% for 0 points, 1% - 25% for 1 point, 26% - 50% for 2 points, 51% - 75% for 3 points, and 76% - 100% for 4 points.

5. The application according to claim 1, characterized in that: The critical value mentioned = 4 points.

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