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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.
Highlights
Hepatocellular carcinoma (HCC) comprises nearly 80% of primary liver cancer and is the sixth most common and fourth deadly malignancy globally (Bray et al, 2018)
The role of some members of S100 protein family members (S100s) in the tumorigenesis and prognosis of several cancers has been partially confirmed, comprehensive understanding the role of twenty S100s in hepatocellular carcinoma (HCC) has yet to be conducted
Our work aims to explore the expression, mutation, prognosis and associations with immune infiltration of S100s in HCC
Summary
Hepatocellular carcinoma (HCC) comprises nearly 80% of primary liver cancer and is the sixth most common and fourth deadly malignancy globally (Bray et al, 2018). Apart from S100A5, S100A7, S100A7A, S100A12, S100A13, S100A16, S100B, S100P, S100G, S100Z, the rest family members, such as S100A1, S100A2, S100A3, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, S100A14, and S100P are shown to be expressed in HCC (Wang et al, 2001; Kittaka et al, 2008; Hua et al, 2011; Luo et al, 2013; Yan et al, 2013; Zhao et al, 2013; De Ponti et al, 2015; Tao et al, 2017; Guo et al, 2018). On the basis of in-depth analysis, we analyzed the expressions, mutations, predictive signaling pathways and associations with immune infiltration of different S100s in patients with HCC and further explored their possible functions, different prognostic roles and the associations with immune infiltrates in HCC
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