Development of an oncogenic dedifferentiation SOX signature with prognostic significance in hepatocellular carcinoma
Mei-Mei Li,
Yun-Qiang Tang,
Yuan-Feng Gong,
Wei Cheng,
Hao-Long Li,
Fan-En Kong,
Wen-Jie Zhu,
Shan-Shan Liu,
Li Huang,
Xin-Yuan Guan,
Ning-Fang Ma,
Ming Liu
Affiliations
Mei-Mei Li
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Yun-Qiang Tang
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Yuan-Feng Gong
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Wei Cheng
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Hao-Long Li
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Fan-En Kong
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Wen-Jie Zhu
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Shan-Shan Liu
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Li Huang
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Xin-Yuan Guan
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Ning-Fang Ma
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Ming Liu
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University
Abstract Background Gradual loss of terminal differentiation markers and gain of stem cell-like properties is a major hall mark of cancer malignant progression. The stem cell pluripotent transcriptional factor SOX family play critical roles in governing tumor plasticity and lineage specification. This study aims to establish a novel SOX signature to monitor the extent of tumor dedifferentiation and predict prognostic significance in hepatocellular carcinoma (HCC). Methods The RNA-seq data from The Cancer Genome Atlas (TCGA) LIHC project were chronologically divided into the training (n = 188) and testing cohort (n = 189). LIRI-JP project from International Cancer Genome Consortium (ICGC) data portal was used as an independent validation cohort (n = 232). Kaplan-Meier and multivariable Cox analyses were used to examine the clinical significance and prognostic value of the signature genes. Results The SOX gene family members were found to be aberrantly expressed in clinical HCC patients. A five-gene SOX signature with prognostic value was established in the training cohort. The SOX signature genes were found to be closely associated with tumor grade and tumor stage. Liver cancer dedifferentiation markers (AFP, CD133, EPCAM, and KRT19) were found to be progressively increased while hepatocyte terminal differentiation markers (ALB, G6PC, CYP3A4, and HNF4A) were progressively decreased from HCC patients with low SOX signature scores to patients with high SOX signature scores. Kaplan-Meier survival analysis further indicated that the newly established SOX signature could robustly predict patient overall survival in both training, testing, and independent validation cohort. Conclusions An oncogenic dedifferentiation SOX signature presents a great potential in predicting prognostic significance in HCC, and might provide novel biomarkers for precision oncology further in the clinic.
