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

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

doi:10.18632/oncotarget.2991

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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is the third leading cause of cancer-related deaths
One of the reasons for the poor prognosis of HCC is the high rate of recurrence due to intrahepatic metastasis or the multicentric development of each neoplastic clone, which can be attributed to the lack of reliable markers for tumor recurrence and metastasis [4]
Using mass spectrometry, Katharina B et al demonstrate that there is no evidence for exchange of PKM1 to pyruvate kinase isoform M2 (PKM2) expression during cancer formation [22]

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is the third leading cause of cancer-related deaths. HCC incidence and mortality are especially high in China [1, 2]. One of the reasons for the poor prognosis of HCC is the high rate of recurrence due to intrahepatic metastasis or the multicentric development of each neoplastic clone, which can be attributed to the lack of reliable markers for tumor recurrence and metastasis [4]. A review of the evidence has supported the general hypothesis that cancer is primarily a disease of energy metabolism [5]. Considerable attention has been paid to the roles of aerobic glycolysis (Warburg effect) in cancer cells [6, 7]

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