Effect Of Tumor-stroma Ratio Of Prognosis Evaluation In Hepatocellular Carcinoma Patients After Liver Transplantation

Background:For a long time, awareness and research of cancer was focused on the tumor cell. However, the studies of tumor stroma and tumor microenvironment were insufficient. In recent years, the role of tumor stroma played in the process of tumor growth, invasion and metastasis drew more and more attention from scholars. Tumor-stroma ratio(TSR) had been upheld as an independent prognostic factor of patients in a variety of solid tumors. However, the prognostic predicting significance of TSR in patients with hepatocellular carcinoma(HCC), especially in those patients underwent liver transplantation was unclear.Methods:This study retrospectively analyzed the data of112patients with hepatocellular carcinoma who underwent liver transplantation in the First Affiliated Hospital of Zhejiang University. Tumor-stroma ratio was evaluated through hematoxylin and eosin (H&E) stained sections. A50%cut-off value was made. Patients were divided into2groups:stroma-rich group(the percentage of stroma≥50%) and stroma-poor group(the percentage<50%). Chi-square test, Kaplan-Meier method and Cox univariable and multivariable regression were used in to analyze the data.Results:Among the112post liver transplantation patients,25patients were stroma-rich, and87were stroma-poor. Chi-square test did not indicate the relation between TSR and gender, age, tumor size, tumor number, differentiation of tumor, pTNM stage, and preoperative AFP. The tumor-stroma ratio was associated with overall survival(OS) in univariate and multivariate analyses (HR:2.92;95%CI:1.63-5.23; HR:2.76;95%CI:1.47-4.85, respectively), and TSR was also associated with recurrence-free survival (RFS) in univariate and multivariate analyses (HR:2.63;95%CI:1.42-4.86; HR:1.93;95%CI:1.03-3.62, respectively). In the field of patient selection for liver transplantation, we found patients with stroma-poor tumor and within Milan criteria, UCSF criteria and Hangzhou criteria had a better prognosis for OS rate and RFS rate.Conclusion:This study indicates that tumor-stroma ratio is an independent prognostic factor for HCC patients who undergo liver transplantation. The patients with stoma-rich tumors suffer a worse prognosis compared with those patients with stroma-poor tumors. In the field of patient selection for liver transplantation, TSR could be combined with Milan criteria, UCSF criteria and Hangzhou criteria to assess the prognosis and screen proper patients for liver transplantation. A prospective study of a large sample is recommended to confirm the prognostic predicting significance of TSR in patients with hepatocellular carcinoma, especially in those patientsunderwent liver transplantation.