Research Paper Volume 12, Issue 4 pp 3431—3450
Development and validation of a prognostic classifier based on HIF-1 signaling for hepatocellular carcinoma
- 1 Department of Liver and Pancreatic Surgery, The Affiliated Foshan Hospital, Sun Yat-Sen University, Foshan 528000, China
- 2 Department of Pancreatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
- 3 Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
- 4 Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510008, China
- 5 Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
- 6 Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Received: November 2, 2019 Accepted: January 27, 2020 Published: February 21, 2020
https://doi.org/10.18632/aging.102820How to Cite
Copyright © 2020 Deng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
HIF-1 (hypoxia-inducible factor 1) signaling played a vital role in HCC (hepatocellular carcinoma) prognosis. We aimed to establish an accurate risk scoring system for HCC prognosis prediction and treatment guidance. 424 samples from TCGA (The Cancer Genome Atlas) and 445 samples from GSE14520 dataset were included as the derivation and validation cohort, respectively. In the derivation cohort, prognostic relevant signatures were selected from sixteen HIF-1 related genes and LASSO regression was adopted for model construction. Tumor-infiltrating immune cells were calculated using CIBERSORT algorithm. HIF-1 signaling significantly increased in HCC samples compared with normal tissues. Scoring system based on SLC2A1, ENO1, LDHA and GAPDH exhibited a continuous predictive ability for OS (overall survival) in HCC patients. PCA and t-SNE analysis confirmed a reliable clustering ability of risk score in both cohorts. Patients were classified into high-risk and low-risk groups and the survival outcomes between the two groups showed significant differences. In the derivation cohort, Cox regression indicated the scoring system was an independent predictor for OS, which was validated in the validation cohort. Different infiltrating immune cells fraction and immune scores were also observed in different groups. Herein, a novel integrated scoring system was developed based on HIF-1 related genes, which would be conducive to the precise treatment of patients.