Prognostic Significance Of The Tumor-stroma Ratio In Gallbladder Cancer

Background and Objective: Gallbladder cancer(GBC)is the most prevalent and aggressive malignancy of the biliary tract.There are no obvious symptoms in patients with gallbladder cancer,so it is difficult to diagnose early.Regional nodal status and the depth of tumor invasion(T status)are the two most important prognostic factors for GBC.The histological subtype of gallbladder cancer is another important prognostic factor.Treatment of the cancer mainly depends on its clinical stage and the characteristics of the tumor cells.However,patients diagnosed at the same stage often have markedly different prognoses.Current research needs to investigate additional prognostic markers.In recent years,the tumor-stroma ratio(TSR)has attracted increasing attention as an independent prognostic factor for several solid tumors.However,the importance of the stromal compartment has not been investigated yet in gallbladder cancer(GBC).The objective of this study is to investigate the prognostic value of TSR in GBC and the relationship between TSR and other known prognostic parameters.Methods: A total of 51 patients who underwent operations for gallbladder carcinoma were selected for this study.These operations included radical operations,cholecystectomy,and palliative resection.Patients who were treated with pre-operative chemotherapy or radiotherapy were excluded.TSR was determined on haematoxylin and eosin(H&E)-stained sections by two independent investigators.The most invasive region of the GBC tumor on each section was analyzed using a 4× objective.The stroma and tumor were then analyzed using a 10× objective.Stromal ratio groups were classified as stroma-poor(ratio of stroma < 50%)and stroma-rich(ratio of stroma >50%).The Mann-Whitney test,the Chi-squared test,the Kaplan-Meier method,and the Cox proportional hazard model were used to analyze the data.All cases of death irrelevant to GBC were censored.The survival curves were analyzed via the Kaplan-Meier method.The log rank test was used to assess the differences between the groups for statistical significance.The Cox proportional hazards model was used to determine the hazard ratio(HR)and 95% confidence intervals(CIs)of variables for OS in univariate and multivariate analysis.Only those variables with statistical significance in univariate analysis were included in multivariate analysis.All statistical tests were 2-sided,and P<0.05 was considered to be statistically significant.Results: The median survival time for patients in the stroma-rich group was 6.00 months(95% CI,4.47–7.54).In contrast,for the stroma-poor group,the median survival time was17.00 months(95% CI,3.64-30.36).The 3-year overall survival rate was 19.7% in the stroma-poor group and 7.2% in the stroma-rich group.Patients with stroma-rich tumors had a worse prognosis than those with stroma-poor tumors(log-rank P=0.004).According to the univariate analysis,the TSR,differentiation grade,p TNM stage,and operative methods were shown to be related to overall survival(OS)with statistical significance.The hazard ratio(HR)of TSR was 2.428(95% CI,1.29-4.58;P=0.006).However,the TSR did not prove to be an independent prognostic factor in the multivariate analysis.Conclusion: Our study demonstrated that the tumor-stroma ratio(TSR)is an important prognostic parameter for gallbladder cancer(GBC).Stroma-rich tumors were associated with poor overall survival.