A Hypoxia and EMT-Related Gene Signature for Predicting Prognosis and Immunotherapy Benefit in Hepatocellular Carcinoma.
4 affiliations
- 1Department of Emergency, Zhengzhou Central Hospital Affiliated with Zhengzhou University, Zhengzhou, People's Republic of China.
- 2Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
- 3Key Laboratory of Precision Diagnosis and Treatment in General Surgical (Hepatobiliary and Pancreatic) Diseases of Health Commission of Henan Province, Zhengzhou, People's Republic of China.
- 4Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
Abstract
Objective
Epithelial-mesenchymal transition (EMT) and hypoxia are key factors in hepatocellular carcinoma (HCC) metastasis and recurrence. This study explored their combined impact on HCC prognosis and immunotherapy benefit.Methods
TCGA, ICGC, and GEO (GSE14520) datasets were analyzed. An EMT-hypoxia prognostic model (EHPM) was built using LASSO, trained on TCGA (n = 365) and validated in ICGC (n = 231) and GSE14520 (n = 221). ROC curves assessed accuracy. ssGSEA and TIDE explored EHPM-tumor immune microenvironment relationships and predicted immunotherapy benefit. Nine EMT/hypoxia-related genes were validated by qRT-PCR in eight paired HCC and adjacent normal liver tissues.Results
The 9-gene EHPM was stable across cohorts. The 1-, 2-, and 3-year AUCs were 0.82, 0.72, and 0.76 in TCGA; 0.717, 0.701, and 0.651 in ICGC; and 0.681, 0.609, and 0.557 in GEO. High-EHPM patients showed advanced TNM stage (p = 0.003), poorer differentiation (p = 0.003), higher vascular invasion (p = 0.002), elevated AFP (p < 0.001), shorter overall survival (TCGA and ICGC: p < 0.0001; GEO: p = 0.013), and immunosuppression. EHPM was an independent prognostic factor (HR = 3.315, 95% CI 2.501-4.215, p < 0.001). TIDE indicated more immune non-responders in the high-EHPM group (p < 7.9e-07), As this is based on computational inference rather than treated patients, it should be regarded as hypothesis-generating. The nomogram predicted OS with AUCs of 0.825, 0.734, and 0.777 at 1, 2, and 3 years. qRT-PCR confirmed upregulation of all nine genes in HCC tissues.Conclusion
This EMT-hypoxia model effectively predicts OS and may help identify HCC patients likely to benefit from immunotherapy, though this requires validation in ICI-treated cohorts.
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BibTeX
@article{hu2026hypoxia,
title = {{A Hypoxia and EMT-Related Gene Signature for Predicting Prognosis and Immunotherapy Benefit in Hepatocellular Carcinoma.}},
author = {Wenhao Hu and Dute Gao and Guojun Hou and Chang Liu and Xianglong Meng and Qinlong Liu and Jiaan Sun},
journal = {Journal of hepatocellular carcinoma},
year = {2026},
month = oct,
doi = {10.2147/jhc.s642054},
url = {https://europepmc.org/article/MED/42921206},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - A Hypoxia and EMT-Related Gene Signature for Predicting Prognosis and Immunotherapy Benefit in Hepatocellular Carcinoma.
AU - Wenhao Hu
AU - Dute Gao
AU - Guojun Hou
AU - Chang Liu
AU - Xianglong Meng
AU - Qinlong Liu
AU - Jiaan Sun
PY - 2026
DA - 2026/10/19
JO - Journal of hepatocellular carcinoma
DO - 10.2147/jhc.s642054
UR - https://europepmc.org/article/MED/42921206
AB - Objective Epithelial-mesenchymal transition (EMT) and hypoxia are key factors in hepatocellular carcinoma (HCC) metastasis and recurrence. This study explored their combined impact on HCC prognosis and immunotherapy benefit.Methods TCGA, ICGC, and GEO (GSE14520) datasets were analyzed. An EMT-hypoxia prognostic model (EHPM) was built using LASSO, trained on TCGA (n = 365) and validated in ICGC (n = 231) and GSE14520 (n = 221). ROC curves assessed accuracy. ssGSEA and TIDE explored EHPM-tumor immune microenvironment relationships and predicted immunotherapy benefit. Nine EMT/hypoxia-related genes were validated by qRT-PCR in eight paired HCC and adjacent normal liver tissues.Results The 9-gene EHPM was stable across cohorts. The 1-, 2-, and 3-year AUCs were 0.82, 0.72, and 0.76 in TCGA; 0.717, 0.701, and 0.651 in ICGC; and 0.681, 0.609, and 0.557 in GEO. High-EHPM patients showed advanced TNM stage (p = 0.003), poorer differentiation (p = 0.003), higher vascular invasion (p = 0.002), elevated AFP (p < 0.001), shorter overall survival (TCGA and ICGC: p < 0.0001; GEO: p = 0.013), and immunosuppression. EHPM was an independent prognostic factor (HR = 3.315, 95% CI 2.501-4.215, p < 0.001). TIDE indicated more immune non-responders in the high-EHPM group (p < 7.9e-07), As this is based on computational inference rather than treated patients, it should be regarded as hypothesis-generating. The nomogram predicted OS with AUCs of 0.825, 0.734, and 0.777 at 1, 2, and 3 years. qRT-PCR confirmed upregulation of all nine genes in HCC tissues.Conclusion This EMT-hypoxia model effectively predicts OS and may help identify HCC patients likely to benefit from immunotherapy, though this requires validation in ICI-treated cohorts.
SN - 2253-5969
ER -