Co-expression of PKM2 and TRIM35 predicts survival and recurrence in hepatocellular carcinoma

Zhiao Chen; Xinyuan Lu; Zhichao Wang; Guangzhi Jin; Qifeng Wang; Di Chen; Taoyang Chen; Jinjun Li; Jia Fan; Wenming Cong; Qiang Gao; Xianghuo He

doi:10.18632/oncotarget.2991

Co-expression of PKM2 and TRIM35 predicts survival and recurrence in hepatocellular carcinoma

Oncotarget. 2015 Feb 10;6(4):2538-48. doi: 10.18632/oncotarget.2991.

Authors

Zhiao Chen¹, Xinyuan Lu², Zhichao Wang³, Guangzhi Jin², Qifeng Wang⁴, Di Chen⁵, Taoyang Chen⁶, Jinjun Li⁵, Jia Fan³, Wenming Cong², Qiang Gao³, Xianghuo He¹

Affiliations

¹ Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
² Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
³ Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
⁴ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁵ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Qi Dong Liver Cancer Institute, Qi Dong, Jiangsu, China.

Abstract

The identification of prognostic markers for hepatocellular carcinoma (HCC) is needed for clinical practice. Tripartite motif-containing 35 (TRIM35) is a tumor suppressor of HCC. TRIM35 inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells. We found that expression of PKM2 was significantly increased in HCC tissues. This overexpression of PKM2 was correlated with a high TNM stage and level of vascular invasion. Patients with HCC who were positive for PKM2 expression and negative for TRIM35 expression had shorter overall survival and time to recurrence than patients who were negative for PKM2 and positive for TRIM35. Furthermore, PKM2/TRIM35 combination was an independent and significant risk factor for recurrence and survival. In conclusion, PKM2 (+) and TRIM35 (-) contribute to the aggressiveness and poor prognosis of HCC. PKM2/TRIM35 expression could be a biomarker for the prognosis of HCC and target for cancer therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / genetics*
Apoptosis Regulatory Proteins / metabolism
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Cohort Studies
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Male
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Middle Aged
Multivariate Analysis
Neoplasm Recurrence, Local
Neoplasm Staging
Prognosis
Proportional Hazards Models
Reverse Transcriptase Polymerase Chain Reaction
Risk Assessment / methods
Risk Assessment / statistics & numerical data
Risk Factors
Survival Analysis
Thyroid Hormone-Binding Proteins
Thyroid Hormones / genetics*
Thyroid Hormones / metabolism

Substances

Apoptosis Regulatory Proteins
Biomarkers, Tumor
Carrier Proteins
Membrane Proteins
TRIM35 protein, human
Thyroid Hormones