Study on the gene signature related to immune microenvironment on viral and nonviral infections of hepatocellular carcinoma.
Biomarkers, Tumor
Carcinoma, Hepatocellular
/ etiology
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Hepatitis
/ complications
Humans
Kaplan-Meier Estimate
Liver Neoplasms
/ etiology
Male
Middle Aged
Neoplasm Staging
Prognosis
RNA, Messenger
/ biosynthesis
Tumor Microenvironment
/ genetics
Journal
Medicine
ISSN: 1536-5964
Titre abrégé: Medicine (Baltimore)
Pays: United States
ID NLM: 2985248R
Informations de publication
Date de publication:
16 Apr 2021
16 Apr 2021
Historique:
received:
02
02
2020
accepted:
10
03
2021
entrez:
13
4
2021
pubmed:
14
4
2021
medline:
29
4
2021
Statut:
ppublish
Résumé
The pathogenesis of hepatocellular carcinoma (HCC) can be divided into viral infection (VIR) and nonviral (NVIR) infection. Two types of HCC performed different tumor immune microenvironment (TIME) which directly affected prognosis of HCC. This study aimed to identify an effective 2 types of HCC prognostic gene signature that related to immune TIME.The differential expression genes (DEGs) were analyzed by Limma R package from the Cancer Genome Atlas. Immune related genes getting from IMMport database were matched to DEGs for testing prognosis. Prognostic index (PI) consisted of prognostic immune related genes was calculated in different types of HCC by COX regression and the correlation with the abundance of immune infiltrates, including 6 type cells, via gene modules. Tumor immune estimation resource database was applied to analyze TIME. Finally, the correlations between PI of DEGs and TIICs were analyzed by the Spearman method.Results showed that PI consisted of 11 messenger RNAs in VIR and 12 messenger RNAs in NVIR groups. The PI related to HCC prognosis has different correlations with immune infiltrating cells in VIR and NVIR groups. The PI value of DEGs has significant correlations with neutrophils (R = 0.22, P-value = .029) and dendritic (R = 0.21, P-value = .036) infiltration levels in VIR group. However, in NVIR group, the result showed there were no significant correlations between PI and other 5 type cell infiltration levels (P-value > .05).The 11-gene signature in VIR and 12-gene signature in NVIR group selected based on data from the Cancer Genome Atlas database had a different correlation with immune infiltrating cells of HCC patients.
Identifiants
pubmed: 33847635
doi: 10.1097/MD.0000000000025374
pii: 00005792-202104160-00031
pmc: PMC8052083
doi:
Substances chimiques
Biomarkers, Tumor
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e25374Informations de copyright
Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors have no funding and conflicts of interest to disclose.
Références
Park C-K, Oh I-J, Kim Y-C. What is currently the best for adenocarcinoma without driver mutation? Tuberc Respir Dis 2018;81:258–9.
Harding JJ, El Dika I, Abou-Alfa GK. Immunotherapy in hepatocellular carcinoma: primed to make a difference? Cancer 2016;122:367–77.
Hagag NA, Ali YBM, Elsharawy AA, et al. Clinical impact of circulated miR-1291 in plasma of patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC): implication on glypican-3 expression. J Gastrointest Cancer 2019;51:234–41.
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359–86.
Galle PR, Forner A, Llovet JM, et al. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2018;69:182–236.
Gao Q, Wang XY, Qiu SJ, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res 2009;15:971–9.
Hernandez-Gea V, Toffanin S, Friedman SL, et al. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology 2013;144:512–27.
Li B, Severson E, Pignon JC, et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol 2016;17:174.
Chang CS, Huang SM, Lin HH, et al. Different expression of apoptotic proteins between HBV-infected and non-HBV-infected hepatocellular carcinoma. Hepatogastroenterology 2007;54:2061–8.
Li T, Fan J, Wang B, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res 2017;77:e108–10.
Aran D, Sirota M, Butte AJ. Systematic pan-cancer analysis of tumour purity. Nat Commun 2015;6:8971.
Hato T, Goyal L, Greten TF, et al. Immune checkpoint blockade in hepatocellular carcinoma: current progress and future directions. Hepatology 2014;60:1776–82.
Mlecnik B, Bindea G, Angell HK, et al. Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity 2016;44:698–711.
Ohtani H. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human colorectal cancer. Cancer Immun 2007;7:4.
Jenne CN, Kubes P. Immune surveillance by the liver. Nat Immunol 2013;14:996–1006.
Nasti TH, Timares L. MC1R, eumelanin and pheomelanin: their role in determining the susceptibility to skin cancer. Photochem Photobiol 2015;91:188–200.
Galdiero MR, Garlanda C, Jaillon S, et al. Tumor associated macrophages and neutrophils in tumor progression. J Cell Physiol 2013;228:1404–12.
Donskov F. Immunomonitoring and prognostic relevance of neutrophils in clinical trials. Semin Cancer Biol 2013;23:200–7.
Zhou SL, Dai Z, Zhou ZJ, et al. Overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma. Hepatology 2012;56:2242–54.
Owusu Sekyere S, Suneetha PV, Kraft AR, et al. A heterogeneous hierarchy of co-regulatory receptors regulates exhaustion of HCV-specific CD8 T cells in patients with chronic hepatitis C. J Hepatol 2015;62:31–40.
Reignat S, Webster GJ, Brown D, et al. Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection. J Exp Med 2002;195:1089–101.
Fisicaro P, Valdatta C, Massari M, et al. Antiviral intrahepatic T-cell responses can be restored by blocking programmed death-1 pathway in chronic hepatitis B. Gastroenterology 2010;138:682–93.e1-4.
Czepielewski RS, Porto BN, Rizzo LB, et al. Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils. Proc Natl Acad Sci U S A 2012;109:547–52.
Schulze K, Imbeaud S, Letouze E, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet 2015;47:505–11.