title: Reduced SOD2 expression is associated with mortality of hepatocellular carcinoma patients in a mutant p53-dependent manner.
abstract: The development and progression of hepatocellular carcinoma (HCC) is accompanied with persistent oxidative stress, but the molecular basis is not well defined. Superoxide dismutase 2 (SOD2) is an important mitochondrial antioxidant and a key aging factor. Here we investigated the expression and clinical significance of SOD2 in a large cohort of HBV-positive HCC tumors. Both SOD2 mRNA and protein are reduced in human primary HCCs compared with matching liver tissues. Consistently, the SOD2 DNA copy numbers are decreased in HCCs, providing a genetic basis for the decrease in SOD2 mRNA expression. Reduced SOD2 expression in HCCs is correlated with older age, larger tumor size, multiple tumor nodules and tumor emboli, and cancer recurrence. Moreover, low SOD2 expression is strongly associated with poor overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate Cox regression analyses indicates that SOD2 is an independent prognostic predictor for OS and RFS. Intriguingly, reduced SOD2 mRNA is strongly associated with poor survival in a separate cohort of HCC patients carrying mutant p53. Altogether, our results provide clinical evidence for the importance of SOD2 in tumor progression and mortality, and the close relationship of SOD2 and p53 in HCC.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, PR China.
authors.forename: Ren
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, PR China.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, PR China.
authors.forename: Xian-Zi
authors.initials: XZ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, PR China.
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, PR China.|Rutgers Cancer Institute of New Jersey, and Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, PR China.|Rutgers Cancer Institute of New Jersey, and Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: X F Steven
authors.initials: XF
authors.lastname: Zheng
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; D000099156:Superoxide Dismutase 2
keywords: Hepatocellular Carcinoma (HCC); Reactive Oxygen Species (ROS); Superoxide Dismutase 2 (SOD2); cancer; liver