Microenvironment characterization and multi-omics signatures related to prognosis and immunotherapy response of hepatocellular carcinoma

Experimental Hematology & Oncology
Furong LiuBixiang Zhang

Abstract

Immune cell infiltration in the tumor microenvironment (TME) affects tumor initiation, patients' prognosis and immunotherapy strategies. However, their roles and interactions with genomics and molecular processes in hepatocellular carcinoma (HCC) still have not been systematically evaluated. We performed unsupervised clustering of total 1000 HCC samples including discovery and validation group from available public datasets. Immune heterogeneity of each subtype was explored by multi-dimension analysis. And a support vector machine (SVM) model based on multi-omics signatures was trained and tested. Finally, we performed immunohistochemistry to verify the immune role of signatures. We defined three immune subtypes in HCC, with diverse clinical, molecular, and genomic characteristics. Cluster1 had worse prognosis, better anti-tumor characteristics and highest immune scores, but also accompanied by immunosuppression and T cell dysfunction. Meanwhile, a better anti-PD1/CTLA4 immunotherapeutic response was predicted in cluster1. Cluster2 was enriched in TAM-M2 and stromal cells, indicating immunosuppression. Cluster3, with better prognosis, had lowest CD8 T cell but highest immune resting cells. Further, based on genomic signatures, ...Continue Reading

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Citations

Nov 26, 2020·Cellular & Molecular Immunology·Benjamin RufTim F Greten
Dec 17, 2020·Journal of Hepatocellular Carcinoma·Miaomiao LiKun Guo
Mar 5, 2021·Cancer Immunology, Immunotherapy : CII·Xian-Ning WuNan Zhang
Mar 30, 2021·Frontiers in Oncology·Yanna LeiMing Liu
Jun 8, 2021·Frontiers in Molecular Biosciences·Yiming LuoZhiwei Zhang
Jun 14, 2021·Experimental Hematology & Oncology·Xi LiWei Wu
Aug 13, 2021·Frontiers in Oncology·Mengke NiuKongming Wu

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Datasets Mentioned

BETA
GSE64041
GSE31384
GSE76427

Methods Mentioned

BETA
protein array
RNA-seq

Software Mentioned

ConsensusClusterPlus
Tumor Immune Dysfunction and Exclusion ( TIDE )
mclust
GSEA
TIDE
CIBERSORT
NbClust
survminer
MCPcounter

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