Identification of TP53 Mutation Associated-Immunotype and Prediction of Survival in Patients with Hepatocellular Carcinoma

Abstract

Background: TP53 gene is one of the most frequent alterations, and heterogeneity in immune cell content is found in hepatocellular carcinoma (HCC). However, TP53 mutations associated immunotype of HCC has not been reported. This study aimed to identify the TP53 mutations associated immunotype. Methods: The mutation annotation format (MAF) document, mRNA expression data and clinical data of HCC patients were downloaded from the publicly available TCGA (The Cancer Genome Atlas) data portal. 332 HCC patients were finally incorporate into this study. Infiltrating immune cells were evaluated by well-known CIBERSORT method. Another mutation data of HCC patients was downloaded from the COSMIC (Catalogue of Somatic Mutations in Cancer) database. Findings: TP53 was the gene harboring the highest frequency of mutations. Subsequently, 5 lethal features including TP53 mutations were screen by LASSO (Least absolute shrinkage and selector operation)-COX regression according to TP53 mutations and 22 infiltrating immune cells. And then, two distinct subgroups of HCC were identified according to previous five lethal features. What's more, the expression levels of co-inhibitory immune checkpoints were significantly up-regulated, and the GO terms or pathways to boost immune responses were found to be inhibited in immunotype B subgroup compared with that in immunotype A subgroup. Finally, the immunotype was proved to be an independent adverse prognostic factor, contribute to improving the predictive accuracy of the immunotype-based model and avoiding excessive medical treatment. Interpretation: Stratification of tumors is paramount to achieve better clinical outcomes. Herein, two distinct immunotypes of HCC in terms of prognosis, phenotype, and function were identified and subverted the traditional understanding of intratumoral CD8+ T cells. Moreover, the immunotypes contributed to improving the predictive accuracy and avoiding excessive medical treatment of some HCC patients. Funding: This study was funded by grants from the National Natural Science Foundation of China (81401988 and 81770266), the Six talent peaks project in Jiangsu Province (WSN-060) and the Key talents of youth medicine in Jiangsu Provincial Department of health (QNRC2016681). Declaration of Interest: The authors have declared that no conflicts of interest exist.