Comprehensive Analysis of the Prognosis and Correlations With Immune Infiltration of S100 Protein Family Members in Hepatocellular Carcinoma

Susu Zheng; Linxia Liu; Tongchun Xue; Chuyu Jing; Xin Xu; Yanfang Wu; Meixia Wang; Xiaoying Xie; Boheng Zhang

doi:10.3389/fgene.2021.648156

Comprehensive Analysis of the Prognosis and Correlations With Immune Infiltration of S100 Protein Family Members in Hepatocellular Carcinoma

Front Genet. 2021 Mar 18:12:648156. doi: 10.3389/fgene.2021.648156. eCollection 2021.

Authors

Susu Zheng^{1

2}, Linxia Liu³, Tongchun Xue², Chuyu Jing², Xin Xu², Yanfang Wu¹, Meixia Wang¹, Xiaoying Xie^{1

2}, Boheng Zhang^{1

2

4}

Affiliations

¹ Xiamen Branch, Department of Hepatic Oncology, Zhongshan Hospital, Fudan University, Xiamen, China.
² Key Laboratory for Carcinogenesis and Cancer Invasion, Zhongshan Hospital, Shanghai Medical School, The Liver Cancer Institute, The Chinese Ministry of Education, Fudan University, Shanghai, China.
³ School of Nursing and Health Management, Shanghai University of Medicine and Health Sciences, Shanghai, China.
⁴ Center for Evidence-Based Medicine, Shanghai Medical School, Fudan University, Shanghai, China.

Abstract

S100 protein family members (S100s) are commonly dysregulated in various tumors including hepatocellular carcinoma (HCC). However, the diverse expression, mutation, prognosis and associations with immune infiltration of S100s in HCC have yet to be analyzed. Herein we investigated the roles of S100s in HCC from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal and TIMER databases. Compared with para-cancer tissues, the expression levels of S100A4/S100A6/S100A10/S100A11/S100A13/S100A14/S100P were higher in HCC tissues, while the expression levels of S100A8/S100A9/S100A12 were decreased in tumor tissues. The mRNA levels of S100A2/S100A7/S100A7A/S100A8/S100A9/S100A11 were correlated with advanced tumor stage. Besides, higher mRNA expressions of S100A6/S100A10/S100A11/S100A13/S100A14/S100P were shown to have shorter overall survival (OS), while higher expression of S100A12 was associated with favorable OS. Further, the mutation rate of S100s was investigated, and the high mutation rate (53%) was associated with shorter OS. Additionally, the expressions of S100s were found to be significantly associated with various immune infiltrating cells. Hence, our results showed that S100A6/S100A10/S100A11/S10012/S100A13/S100A14/S100P may be regarded as new prognostic or therapeutic markers and S100s inhibitors may be helpful in the combination of immunotherapies.

Keywords: S100 protein family; hepatocellular carcinoma; immune infiltrates; mutations; prognosis.