Secreted phosphoprotein 1 (SPP1) functions in several physiological processes. The role of SPP1 expression in the prognosis and tumor immunity of hepatocellular carcinoma (HCC) is unknown. The aim of this study was to investigate the expression pattern of SPP1 in HCC and its correlation with prognosis and tumor immunity.

Clinical and gene expression data of The Cancer Genome Atlas-liver hepatocellular carcinoma (LIHC) cohort and 11 other HCC datasets were collected. The Kaplan-Meier method and Cox regression analysis were used to analyze the prognostic value of SPP1. The DESeq2 package in R was used to analyze SPP1-related genes. Gene Ontology analysis and gene set enrichment analysis were used to determine the biological function of SPP1 in HCC. The single sample Gene Set Enrichment Analysis (ssGSEA) method was used to analyze the immune infiltrates of HCC. Illumina human methylation 450 data and level 3 HTSeq-FPKM data from The Cancer Genome Atlas-LIHC were used to analyze the effects of DNA methylation level on SPP1 expression.

SPP1 was overexpressed in HCC and correlated with T stage, histological grade, adjacent hepatic tissue inflammation, and vascular invasion in HCC. The analysis of survival rates indicated that high SPP1 levels were associated with poor overall survival in HCC. Functional analysis showed that SPP1 is related to tumor immunity, especially macrophage infiltration. Aberrant demethylation of the promoter region is one of the mechanisms underlying the increase of SPP1 in HCC.

Our results indicate that SPP1 is an independent prognostic factor for HCC and is correlated with the clinical features and macrophage infiltration in HCC.