Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2024; 16(3): 439-451
Published online Mar 27, 2024. doi: 10.4254/wjh.v16.i3.439
Comprehensive prognostic and immune analysis of sterol O-acyltransferase 1 in patients with hepatocellular carcinoma
Chang-Jiao Gan, Yue Zheng, Bin Yang, Li-Min Cao
Chang-Jiao Gan, Development Research Department, National Medical Products Administration Institute of Executive Development, Beijing 100071, China
Yue Zheng, School of Medicine, Nankai University Affiliated Third Center Hospital, Tianjin 300070, China
Bin Yang, Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin 300170, China
Li-Min Cao, Department of Science and Technology, Tianjin Third Central Hospital, Tianjin 300170, China
Co-first authors: Chang-Jiao Gan and Yue Zheng.
Co-corresponding authors: Li-Min Cao and Bin Yang.
Author contributions: Gan CJ, Zheng Y, Cao LM, and Yang B conceptualized and designed the research; Gan CJ and Zheng Y performed data analysis; Gan CJ and Zheng Y wrote the paper. All the authors have read and approved the final manuscript. Both Gan CJ and Zheng Y have made crucial and indispensable contributions towards the completion of the project and thus are qualified as the co-first authors of the paper. Both Cao LM and Yang B have played important and indispensable roles in the study design, and manuscript preparation as the co-corresponding authors. Both Cao LM and Yang B applied for and obtained the funds for this research project. Cao LM conceptualized, designed, and supervised the whole process of the project. She searched the literature, and revised and submitted the early version of the manuscript. Yang B was instrumental and responsible for data re-analysis and re-interpretation, figure plotting, comprehensive literature search, and preparation and submission of the current version of the manuscript. This collaboration between Cao LM and Yang B is crucial for the publication of this manuscript and other manuscripts still in preparation.
Supported by the Tianjin Municipal Project of Science and Technology, No. 21ZXGWSY00040; and the Tianjin Health Research Project, No. TJWJ2022QN043.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of Tianjin Third Central Hospital.
Informed consent statement: Consent was not needed as the study was retrospective without exposure to the patients’ data.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li-Min Cao, PhD, Adjunct Associate Professor, Department of Science and Technology, Tianjin Third Central Hospital, No. 83 Jintang Road, Hedong District, Tianjin 300170, China. rosemary1993@139.com
Received: November 8, 2023
Peer-review started: November 8, 2023
First decision: November 30, 2023
Revised: December 22, 2023
Accepted: February 18, 2024
Article in press: February 18, 2024
Published online: March 27, 2024
Processing time: 140 Days and 4.8 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) has a poor prognosis and heavy disease burden, but its treatment methods are not satisfactory.

Research motivation

High sterol O-acyltransferase 1 (SOAT1) expression has been shown to be associated with several tumor types (liver cancer, pancreatic cancer, and prostate cancer) and with diagnosis and treatment. However, the relationship between SOAT1 expression and HCC remains unclear. As patients would greatly benefit from early detection of HCC, the complementary study of HCC-associated proteins in serum samples using state-of-the-art proteomics would also be a very attractive direction for future research. Therefore, SOAT1 may serve as a novel target that drives the development of immunotherapy and metabolic therapy.

Research objectives

This study aimed to investigate the correlation between SOAT1 expression and HCC, using RNA-seq and gene expression data of The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) and pan-cancer. Our findings demonstrate that SOAT1 may serve as a new target for HCC treatment and promote the development of new strategies for immunotherapy and metabolic therapy.

Research methods

The correlation between SOAT1 expression and HCC was analyzed. Cox hazard regression models were used to investigate the prognostic value of SOAT1. Overall survival and disease-specific survival were also explored in TCGA-LIHC. Moreover, the biological processes and functional pathways regulated by SOAT1 were characterized using gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. To better understand the regulatory mechanism of SOAT1 in HCC, protein–protein interaction network and co-expression analyses of SOAT1 in HCC were conducted.

Research results

SOAT1 and SOAT2 were highly expressed in unpaired samples, while only SOAT1 was highly expressed in paired samples. The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748, while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676. Patients with higher SOAT1 expression had lower survival rates. Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway, the IL-18 signaling pathway, the calcium signaling pathway, secreted factors, the Wnt signaling pathway, the Jak/STAT signaling pathway, the MAPK family signaling pathway, and cell–cell communication were involved in such association. SOAT1 expression was positively associated with the abundance of macrophages, Th2 cells, T helper cells, CD56bright natural killer cells, and Th1 cells, and negatively linked to the abundance of Th17 cells, dendritic cells, and cytotoxic cells.

Research conclusions

As patients would greatly benefit from early detection of hepatocellular carcinoma, the complementary study of hepatocellular carcinoma-associated proteins in serum samples using state-of-the-art proteomics would be a very attractive direction for future exploration.

Research perspectives

The identification of other HCC proteins involved in this multigenic heterogeneous cancer type is an important objective for future research.