Dataset Information

Hypoxia Molecular Characterization in Hepatocellular Carcinoma Identifies One Risk Signature and Two Nomograms for Clinical Management.

ABSTRACT: Hypoxia is a universal feature in the tumor microenvironment (TME). Nonetheless, the heterogeneous hypoxia patterns of TME have still not been elucidated in hepatocellular carcinoma (HCC). Using consensus clustering algorithm and public datasets, we identified heterogeneous hypoxia subtypes. We also revealed the specific biological and clinical characteristics via bioinformatic methods. The principal component analysis algorithm was employed to develop a hypoxia-associated risk score (HARS). We identified the two hypoxia subtypes: low hypoxia pattern (C1) and high hypoxia pattern (C2). C1 was less sensitive to immunotherapy compared to C2, consistent with the lack of immune cells and immune checkpoints (ICPs) in C1, whereas C2 was the opposite. C2 displayed worse prognosis and higher sensitivity to obatoclax relative to C1, while C1 was more sensitive to sorafenib. The two subtypes also demonstrated subtype-specific genomic variations including mutation, copy number alteration, and methylation. Moreover, we developed and validated a risk signature: HARS, which had excellent performance for predicting prognosis and immunotherapy. We revealed two hypoxia subtypes with distinct biological and clinical characteristics in HCC, which enhanced the understanding of hypoxia pattern. The risk signature was a promising biomarker for predicting prognosis and immunotherapy.

SUBMITTER: Liu Z

PROVIDER: S-EPMC7846409 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Hypoxia Molecular Characterization in Hepatocellular Carcinoma Identifies One Risk Signature and Two Nomograms for Clinical Management.

Liu Zaoqu Z Liu Long L Lu Taoyuan T Wang Libo L Li Zhaonan Z Jiao Dechao D Han Xinwei X

Journal of oncology 20210120

Hypoxia is a universal feature in the tumor microenvironment (TME). Nonetheless, the heterogeneous hypoxia patterns of TME have still not been elucidated in hepatocellular carcinoma (HCC). Using consensus clustering algorithm and public datasets, we identified heterogeneous hypoxia subtypes. We also revealed the specific biological and clinical characteristics via bioinformatic methods. The principal component analysis algorithm was employed to develop a hypoxia-associated risk score (HARS). We ...[more]

PMID: 33552157

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Project description:Background: Ferroptosis, as a unique programmed cell death modality, has been found to be closely related to the occurrence and development of hepatocellular carcinoma (HCC). Hypoxia signaling pathway has been found to be extensively involved in the transformation and growth of HCC and to inhibit anti-tumor therapy through various approaches. However, there is no high-throughput study to explore the potential link between ferroptosis and hypoxia, as well as their combined effect on the prognosis of HCC. Methods: We included 370 patients in The Cancer Genome Atlas (TCGA) database and 231 patients in the International Cancer Genome Consortium (ICGC) database. Univariate COX regression and Least Absolute Shrinkage and Selection Operator approach were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (FHPS). Kaplan-Meier method and Receiver Operating Characteristic curves were analyzed to evaluate the predictive capability of FHPS. CIBERSOR and single-sample Gene Set Enrichment Analysis were used to explore the connection between FHPS and tumor immune microenvironment. Immunohistochemical staining was used to compare the protein expression of prognostic FRGs and HRGs between normal liver tissue and HCC tissue. In addition, the nomogram was established to facilitate the clinical application of FHPS. Results: Ten FRGs and HRGs were used to establish the FHPS. We found consistent results in the TCGA training cohort, as well as in the independent ICGC validation cohort, that patients in the high-FHPS subgroup had advanced tumor staging, shorter survival time, and higher mortality. Moreover, patients in the high-FHPS subgroup showed ferroptosis suppressive, high hypoxia, and immunosuppression status. Finally, the nomogram showed a strong prognostic capability to predict overall survival (OS) for HCC patients. Conclusion: We developed a novel prognostic signature combining ferroptosis and hypoxia to predict OS, ferroptosis, hypoxia, and immune status, which provides a new idea for individualized treatment of HCC patients.

Dataset Information

Hypoxia Molecular Characterization in Hepatocellular Carcinoma Identifies One Risk Signature and Two Nomograms for Clinical Management.

Publications

Hypoxia Molecular Characterization in Hepatocellular Carcinoma Identifies One Risk Signature and Two Nomograms for Clinical Management.

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