Establishment of a prognostic signature based on fatty acid metabolism genes in HCC associated with hepatitis B.

Publisher: BioMed Central Country of Publication: England NLM ID: 100968547 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-230X (Electronic) Linking ISSN: 1471230X NLM ISO Abbreviation: BMC Gastroenterol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Carcinoma, Hepatocellular*/genetics ; Liver Neoplasms*/genetics ; Hepatitis B*/complications ; Hepatitis B*/genetics; Humans ; Prognosis ; Hepatitis B virus/genetics ; Fatty Acids ; Tumor Microenvironment

Background: Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is one of the most common and deadly cancer and often accompanied by varying degrees of liver damage, leading to the dysfunction of fatty acid metabolism (FAM). This study aimed to investigate the relationship between FAM and HBV-associated HCC and identify FAM biomarkers for predicting the prognosis of HBV-associated HCC.
Methods: Gene Set Enrichment Analysis (GSEA) was used to analyze the difference of FAM pathway between paired tumor and adjacent normal tissue samples in 58 HBV-associated HCC patients from the Gene Expression Omnibus (GEO) database. Next, 117 HBV-associated HCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to establish a prognostic signature based on 42 FAM genes. Then, the prognostic signature was validated in an external cohort consisting of 30 HBV-associated HCC patients. Finally, immune infiltration analysis was performed to evaluate the FAM-related immune cells in HBV-associated HCC.
Results: As a result, FAM pathway was clearly downregulated in tumor tissue of HBV-associated HCC, and survival analysis demonstrated that 12 FAM genes were associated with the prognosis of HBV-associated HCC. Lasso-penalized Cox regression analysis identified and established a five-gene signature (ACADVL, ACAT1, ACSL3, ADH4 and ECI1), which showed effective discrimination and prediction for the prognosis of HBV-associated HCC both in the TCGA cohort and the validation cohort. Immune infiltration analysis showed that the high-risk group, identified by FAM signature, of HBV-associated HCC had a higher ratio of Tregs, which was associated with the prognosis.
Conclusions: Collectively, these findings suggest that there is a strong connection between FAM and HBV-associated HCC, indicating a potential therapeutic strategy targeting FAM to block the accumulation of Tregs into the tumor microenvironment of HBV-associated HCC.
(© 2023. The Author(s).)

Mol Cell. 2012 May 25;46(4):461-71. (PMID: 22633490)
Cell Metab. 2016 Jan 12;23(1):27-47. (PMID: 26771115)
Cells. 2021 Jul 06;10(7):. (PMID: 34359884)
Cancer Metab. 2022 Oct 3;10(1):14. (PMID: 36192773)
CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
FEBS J. 2017 Oct;284(19):3132-3144. (PMID: 28444969)
Clin Cancer Res. 2007 Nov 1;13(21):6275-83. (PMID: 17975138)
BMC Cancer. 2020 Dec 7;20(1):1204. (PMID: 33287761)
J Biol Chem. 2005 Sep 30;280(39):33157-64. (PMID: 16081420)
BMC Med. 2017 Dec 7;15(1):214. (PMID: 29212479)
Clin Transl Oncol. 2022 May;24(5):864-874. (PMID: 35001339)
Nat Biotechnol. 2019 Jul;37(7):773-782. (PMID: 31061481)
Nat Rev Clin Oncol. 2019 Jul;16(7):425-441. (PMID: 30914826)
Immunity. 2015 Sep 15;43(3):435-49. (PMID: 26377897)
Oncogene. 2020 Mar;39(11):2437-2449. (PMID: 31974474)
Natl Sci Rev. 2014 Jul 14;1(3):396-412. (PMID: 25741453)
CA Cancer J Clin. 2018 Jan;68(1):7-30. (PMID: 29313949)
Cell Mol Life Sci. 2007 Feb;64(4):498-505. (PMID: 17279314)
Genomics. 1994 Sep 1;23(1):223-8. (PMID: 7829074)
FEBS Lett. 1998 Apr 17;426(2):187-90. (PMID: 9599005)
Biosci Rep. 2020 Apr 30;40(4):. (PMID: 32286604)
J Virol. 2011 Nov;85(22):11646-54. (PMID: 21917952)
CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. (PMID: 26808342)
Cancer Discov. 2021 May;11(5):1067-1081. (PMID: 33504580)
J Hepatol. 2019 Apr;70(4):615-625. (PMID: 30529504)
Trends Biochem Sci. 2006 Jan;31(1):64-71. (PMID: 16356722)
J Innate Immun. 2020;12(1):31-46. (PMID: 31786568)
Mol Oncol. 2020 Dec;14(12):3135-3152. (PMID: 33030783)
Clin Gastroenterol Hepatol. 2021 Jan;19(1):46-60.e8. (PMID: 32360825)
PLoS One. 2014 Jan 30;9(1):e87011. (PMID: 24498011)
Nat Rev Cardiol. 2021 Dec;18(12):824-837. (PMID: 34253911)
Eur J Cancer. 2019 Nov;121:154-171. (PMID: 31581056)
Med Oncol. 2012 Dec;29(4):2737-43. (PMID: 22147505)
Dev Cell. 2021 May 17;56(10):1363-1393. (PMID: 33945792)
Semin Liver Dis. 2010 Feb;30(1):3-16. (PMID: 20175029)
Nat Rev Cancer. 2021 Dec;21(12):753-766. (PMID: 34417571)
Nat Rev Dis Primers. 2021 Jan 21;7(1):6. (PMID: 33479224)
Chin Med J (Engl). 2017 Nov 20;130(22):2650-2660. (PMID: 29133751)
BMC Cancer. 2021 Apr 20;21(1):436. (PMID: 33879119)
Am J Hum Genet. 1995 Aug;57(2):273-83. (PMID: 7668252)
J Clin Invest. 2019 Jul 2;129(8):3006-3017. (PMID: 31264969)

Keywords: Fatty acid metabolism; HBV; Hepatocellular carcinoma; Prognosis; Tregs

0 (Fatty Acids)

Date Created: 20231114 Date Completed: 20231115 Latest Revision: 20231116

20231215

PMC10644542

10.1186/s12876-023-03026-5

37957550