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Original Article | Open Access

A high level of secreted phosphoprotein 1 is associated with macrophage infiltration and poor prognosis in hepatocellular carcinoma

Jianping Songa,1, Jingxian Sunb,1, Shuhong Jingb, Tingxiao Zhangc, Jianlei Wangc, Yanfeng Liud( )
Department of Hepatobiliary Surgery, Second Hospital of Shandong University, Jinan 250012, China
Department of Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250012, China
Department of Organ Transplantation, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, China

1 These authors contributed equally to this work.

Show Author Information

Abstract

Background and aims

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.

Methods

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.

Results

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.

Conclusion

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

Keywords

Hepatocellular carcinomaPrognosisSecreted phosphoprotein 1Promoter demethylationTumor immunity

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iLIVER
Volume 2 Issue 1,
March 2023
Pages 26-35
DOI: 10.1016/j.iliver.2023.01.004
Cite this article:
Song J, Sun J, Jing S, et al. A high level of secreted phosphoprotein 1 is associated with macrophage infiltration and poor prognosis in hepatocellular carcinoma. iLIVER, 2023, 2(1): 26-35. https://doi.org/10.1016/j.iliver.2023.01.004

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Received: 11 December 2022
Revised: 06 January 2023
Accepted: 27 January 2023
Published: 19 February 2023
© 2023 The Author(s). Published by Elsevier Ltd on behalf of Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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