Panel of significant risk factors predicts early stage gastric cancer and indication of poor prognostic association with pathogens and microsatellite stability

Abstract

Background: There are very few studies covering the epidemiological risk factors associated with Epstein Barr Virus (EBV) and Microsatellite stability for Gastric Cancer (GC) cases. Early diagnosis of GC through epidemiological risk factors is very necessary for the clinical assessment of GC. The aim of this study was to find out the major risk factors to predict GC in early stage and the impact of pathogen infection and MSI on survival rate of patients. GC samples were screened for Helicobacter pylori, Epstein Barr Virus, and Mismatch repair (MMR) gene status (microsatellite stable or instable). Chi-square and logistic regression analysis of Odd ratio and 95% confidence interval (OR, 95% CI) were performed to find out the association between epidemiological factors and the risk of gastric cancer. The pathogen and MMR gene status were analysed to predict their effect on overall survival and the risk score and hazard ratio was calculated for prognostic assessment.

Results: Excess body weight, consumption of extra salt, smoked food, alcohol, and smoking were the major risk factors for GC development. This study achieved a high area under the curve (AUC 0.94) for the probable GC patients in early-stage using the five-panel epidemiological risk factors. H. pylori infected cases were significant with smoked food, while EBV was found to be associated with tuibur intake and smoked food. In overall survival analysis EBV infected and microsatellite stable (HR: 1.32 and 1.34 respectively) GC cases were showing poor prognosis.

Conclusion: This study might provide new opportunities for personalized treatment options using this epidemiological factor risk score and clinicopathological factors assessment for early detection and prognosis in high-risk GC populations.

Keywords: Clinicopathological data; EBV; Gastric Cancer; H. pylori; MSI; Risk factors.

Fig. 1

Study design for the epidemiological risk factors and prognostic assessments for H. pylori, EBV and MMR gene status among gastric cancer patient group

Fig. 2

Frequency distributions of each demographic factors in the gastric cancer patients (pink ribbon) and healthy control (blue ribbon) groups in study cohort. The data were visualized via Circos software. The frequency of occurrence of different demographic factors association with gastric cancer and heathy control groups is depicted in the outer ring. The inner ring of circos plot depicts the subject number exposed with different demographic risk factors. Each factor has been assigned a specific color. The arc originates from gastric cancer and healthy control groups and terminates at different demographical factors to compare the association between the origin and terminating factors. The area of each colored ribbon depicts the frequency of the samples

Fig. 3

Estimation of accuracy value of the significant epidemiological factors based on the logistic model between gastric cancer and healthy control samples a Water fall plot and risk score estimation for stage-I, II, III and IV samples, b Receiver operating curve (ROC) and accuracy estimation of epidemiological factors panel (BMI, extra salt consumptions, smoked food consumptions, alcohol drinking and smoking) c Significant association of the estimated probability values of the epidemiological factors panel between gastric cancer (n = 73) and healthy controls (n = 157), d Water fall plot and risk score estimation for stage-I and II samples, e Receiver operating curve (ROC) and accuracy estimation of epidemiological factors panel. f Significant association of the estimated probability values of the epidemiological factors panel between stage-I and II gastric cancer (n = 30) and healthy controls (n = 157)

Fig. 4

Association of overall survival probability and demographic factors with H. pylori infection, EBV infection and MMR gene status in gastric cancer patients. Odd ratios and 95% confidence interval of the demographic factors presented for the H. pylori (a), EBV (c) and MMR gene status (e). Association between overall survival and the H. Pylori (g) and MMR gene status (h) in TCGA-STAD cohort. EBV status could not be analyzed due to less sample size in TCGA-STAD dataset

Fig. 5

Flow chart depicting the Major risk factors in the present study and their mechanism of Gastric Carcinogenesis from Literature review. The numerical in parenthesis [] represents the bibliographic information