Highlights
- •An EMT-related genes prognostic index could predict HCC prognosis.
- •The cluster C1 patients responded well to immune checkpoint inhibitors.
- •The cluster C2 patients were sensitive to chemotherapeutic and antiangiogenic agents.
Abstract
Epithelial-mesenchymal transition (EMT) contributes to high tumor heterogeneity and
the immunosuppressive environment of the HCC tumor microenvironment (TME). Here, we
developed EMT-related genes phenotyping clusters and systematically evaluated their
impact on HCC prognosis, the TME, and drug efficacy prediction. We identified HCC
specific EMT-related genes using weighted gene co-expression network analysis (WGCNA).
An EMT-related genes prognostic index (EMT-RGPI) capable of effectively predicting
HCC prognosis was then constructed. Consensus clustering of 12 HCC specific EMT-related
hub genes uncovered two molecular clusters C1 and C2. Cluster C2 preferentially associated
with unfavorable prognosis, higher stemness index (mRNAsi) value, elevated immune
checkpoint expression, and immune cell infiltration. The TGF-β signaling, EMT, glycolysis,
Wnt β-catenin signaling, and angiogenesis were markedly enriched in cluster C2. Moreover,
cluster C2 exhibited higher TP53 and RB1 mutation rates. The TME subtypes and tumor
immune dysfunction and exclusion (TIDE) score showed that cluster C1 patients responded
well to immune checkpoint inhibitors (ICIs). Half-maximal inhibitory concentration
(IC50) revealed that cluster C2 patients were more sensitive to chemotherapeutic and
antiangiogenic agents. These findings may guide risk stratification and precision
therapy for HCC patients.
Keywords
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Article info
Publication history
Published online: March 18, 2023
Accepted:
March 16,
2023
Received in revised form:
February 28,
2023
Received:
December 3,
2022
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
