Research Paper Volume 13, Issue 8 pp 11257—11280
Prognostic analysis of tumor mutation burden and immune infiltration in hepatocellular carcinoma based on TCGA data
- 1 Department of Minimally Invasive and Interventional Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
- 2 Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital Affiliated with Jinan University), Jinan University, Zhuhai 519000, China
- 3 Department of Pharmacy, Guangdong Women and Children Hospital, Guangzhou 511400, China
Received: September 24, 2020 Accepted: January 14, 2021 Published: April 4, 2021
https://doi.org/10.18632/aging.202811How to Cite
Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
In order to explore the prognosis of tumor mutation burden (TMB) and the relationship with tumor infiltrating immune cells in hepatocellular carcinoma (HCC), we downloaded somatic mutation data and transcriptome profiles of 376 HCC patients from The Cancer Genome Atlas (TCGA) cohort. We divided the samples into high-TMB and low-TMB groups. A higher TMB level indicated improved overall survival (OS) and was associated with early pathological stages. One hundred and nine differentially expressed genes (DEGs) were identified in HCC. Moreover, based on four hub TMB-related signatures, we constructed a TMB Prognostic model (TMBPM) that possessed good predictive value with area under curve (AUC) of 0.701. HCC patients with higher TMBPM scores showed worse OS outcomes (p < 0.0001). Moreover, DCs subsets not only revealed higher infiltrating abundance in the high-TMB group, but also correlated with worse OS and hazard risk for high-TMB patients in HCC. Meanwhile, CD8+ T cells and B cells were associated with improved survival outcomes. In sum, high TMB indicates good prognosis for HCC and promotes HCC immune infiltration. Hence, DCs and the four hub TMB-related signatures can be used for predicting the prognosis in HCC as supplements to TMB.
Abbreviations
HCC: hepatocellular carcinoma; GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; DEGs: differentially expressed genes; TIMER: Tumor Immune Estimation Resource; PPI: protein–protein interaction; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; OS: overall survival; DFI: disease-free interval; TMB: tumor mutation burden; TMBPM: tumor mutation burden prognostic model; ECM: extracellular matrix; TME: tumor microenvironment; DC: dendritic cell; Tregs: T cells regulatory; GSEA: Gene set enrichment analysis; AUC: area under curve; ROC: receiver operating characteristic; ICIs: immune checkpoint inhibitors; ORR: objective response rate; NES: normalized enrichment score; PD-1: programmed death 1 PD-1; PD-L1: programmed death ligand-1; CTLA-4: cytotoxic T-lymphocyte associated antigen-4; DDR: DNA damage repair; ORR: objective response rate; DEL: deletion; INS: insertion; SNV: single nucleotide variants; FDR: false discovery; PPAR: peroxisome proliferators-activated receptor; LGALS3: lectin galactoside-binding soluble 3; NPIPB15: Nuclear Pore Complex Interacting Protein Family Member B15; FTCD: Formimidoyltransferase Cyclodeaminase; DCN: Decorin; MDSCs: myeloid-derived suppressor cells; mDC: myeloid DC; LDC: lymphatic dendritic cells; pDC: plasmacytoid dendritic cells; ccRCC: clear cell renal cell carcinoma; BLCA: bladder cancer.