NDLI: Identification of a prognostic and therapeutic immune signature associated with hepatocellular carcinoma

Content Provider	Springer Nature : BioMed Central
Author	Peng, Yanan Liu, Chang Li, Mengting Li, Wenjie Zhang, Mengna Jiang, Xiang Chang, Ying Liu, Lan Wang, Fan Zhao, Qiu
Abstract	Background Hepatocellular carcinoma (HCC) is one of the most prevalent and inflammation-associated cancers. The tumor microenvironment (TME) plays an essential role in HCC development and metastasis, leading to poor prognosis. The overall TME immune cells infiltration characterizations mediated by immune-related genes (IRGs) remain unclear. In this study, we aimed to investigate whether immune-related genes could be indicators for the prognosis of HCC patients and TME cell infiltration characterization as well as responses to immunotherapy. Methods We obtained differentially expressed immune-related genes (DE IRGs) between normal liver tissues and liver cancer tissues from The Cancer Genome Atlas (TCGA) database. To identify the prognostic genes and establish an immune risk signature, we performed univariable Cox regression survival analysis and the Least Absolute Shrinkage and Selector Operation (LASSO) regression based on the DE IRGs by robust rank aggregation method. Cox regression analysis was used to identify independent prognostic factors in HCC. We estimated the immune cell infiltration in TME via CIBERSORT and immunotherapy response through TIDE algorithm. Results We constructed an immune signature and validated its predictive capability. The immune signature included 7 differentially expressed IRGs: BIRC5, CACYBP, NR0B1, RAET1E, S100A8, SPINK5, and SPP1. The univariate and multivariate cox analysis showed that the 7-IRGs signature was a robust independent prognostic factor in the overall survival of HCC patients. The 7-IRG signature was associated with some clinical features, including gender, vascular invasion, histological grade, clinical stage, T stage. We also found that the 7-IRG signature could reflect the infiltration characterization of different immunocytes in the tumor microenvironment (TME) and had a good correlation with immune checkpoint molecules, revealing that the poor prognosis might be partly due to immunosuppressive TME. The Tumour Immune Dysfunction and Exclusion (TIDE) analysis data showed that the 7-IRG signature had great potential for indicating the immunotherapy response in HCC patients. The mutation analysis demonstrated a significant difference in the tumor mutation burden (TMB) between the high- and low-risk groups, partially explaining this signature's predictive value. Conclusion In a word, we constructed and validated a novel, immune-related prognostic signature for HCC patients. This signature could effectively indicate HCC patients' survival and immunotherapy response. And it might act as potential immunotherapeutic targets for HCC patients.
Related Links	https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-021-01792-4.pdf
Ending Page	21
Page Count	21
Starting Page	1
File Format	HTM / HTML
ISSN	14752867
DOI	10.1186/s12935-021-01792-4
Journal	Cancer Cell International
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2021-02-10
Access Restriction	Open
Subject Keyword	Cancer Research Cell Biology Immune risk signature Hepatocellular carcinoma Immune cells infiltration Tumor immune microenvironment Differentially expressed immune-related genes Immune checkpoint inhibitor
Content Type	Text
Resource Type	Article
Subject	Cancer Research Genetics Oncology
Journal Impact Factor	5.3/2023
5-Year Journal Impact Factor	5/2023

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