Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma.

Autor:	Zhu XR; Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.; Department of Medical Oncology, Affiliated Kunshan Hospital of Jiangsu University, Medical School of Jiangsu University, Kunshan, China., Zhu JQ; Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.; Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases and Research Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China., Chen YF; Department of Hepatology, Infectious Diseases Hospital Affiliated with Soochow University, Suzhou, China., Liu YY; Clinical Research and Lab Center, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China., Lu JJ; Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China., Sun J; Department of Medical Oncology, Affiliated Kunshan Hospital of Jiangsu University, Medical School of Jiangsu University, Kunshan, China., Peng SQ; Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.; Department of Medical Oncology, Affiliated Kunshan Hospital of Jiangsu University, Medical School of Jiangsu University, Kunshan, China., Chen MB; Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China., Du YP; Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Aug 02; Vol. 12, pp. 972744. Date of Electronic Publication: 2022 Aug 02 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.972744
Abstrakt:	Background: Liver cancer is among the leading causes of death related to cancer around the world. The most frequent type of human liver cancer is hepatocellular carcinoma (HCC). Fatty acid (FA) metabolism is an emerging hallmark that plays a promoting role in numerous malignancies. This study aimed to discover a FA metabolism-related risk signature and formulate a better model for HCC patients' prognosis prediction. Methods: We collected mRNA expression data and clinical parameters of patients with HCC using the TCGA databases, and the differential FA metabolism-related genes were explored. To create a risk prognostic model, we carried out the consensus clustering as well as univariate and multivariate Cox regression analyses. 16 genes were used to establish a prognostic model, which was then validated in the ICGC dataset. The accuracy of the model was performed using receiver operating characteristic (ROC) analyses, decision curve analysis (DCA) and nomogram. The immune cell infiltration level of risk genes was evaluated with single-sample GSEA (ssGSEA) algorithm. To reflect the response to immunotherapy, immunophenoscore (IPS) was obtained from TCGA-LIHC. Then, the expression of the candidate risk genes (p < 0.05) was validated by qRT-PCR, Western blotting and single-cell transcriptomics. Cellular function assays were performed to revealed the biological function of HAVCR1. Results: According to the TCGA-LIHC cohort analysis, the majority of the FA metabolism-related genes were expressed differentially in the HCC and normal tissues. The prognosis of patients with high-risk scores was observed to be worse. Multivariate COX regression analysis confirmed that the model can be employed as an independent prognosis factor for HCC patients. Furthermore, ssGSEA analysis revealed a link between the model and the levels of immune cell infiltration. Our model scoring mechanism also provides a high predictive value in HCC patients receiving anti-PDL1 immunotherapy. One of the FA metabolism-related genes, HAVCR1, displays a significant differential expression between normal and HCC cell lines. Hepatocellular carcinoma cells (Huh7, and HepG2) proliferation, motility, and invasion were all remarkably inhibited by HAVCR1 siRNA. Conclusion: Our study identified a novel FA metabolism-related prognostic model, revealing a better potential treatment and prevention strategy for HCC. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Zhu, Zhu, Chen, Liu, Lu, Sun, Peng, Chen and Du.)
Databáze:	MEDLINE
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