Clinicopathological and prognostic significance of PKM2 protein expression in cirrhotic hepatocellular carcinoma and non-cirrhotic hepatocellular carcinoma

Yan Liu,Xiaoli Yang,Changping Li,Hao Wu,Jianping Gong,Xiong Ding,Ying Mei,Mingming Deng

doi:10.1038/s41598-017-14813-y

Abstract

Pyruvate kinase M2 (PKM2), a key protein in glucose and lipid metabolism, has been reported to be related to carcinogenesis in various malignancies. However, its roles in hepatocellular carcinoma with cirrhotic liver (CL) and hepatocellular carcinoma with non-cirrhoticliver (NCL) haves not been investigated. In our study western bloting, qRT-PCR and immunohistochemistry were performed to evaluate the clinical significance of PKM2 protein expression in CL and NCL. The results revealed that PKM2 protein expression was significantly higher in HCC tissues than in their adjacent non-tumour tissues. The high expression rates of PKM2 were more frequently noted in CL (45. 6%) than in NCL (31. 9%) tissues. High PKM2 expression in CL and NCL tissues was significantly associated with vascular invasion (P = 0.002 and P = 0.004, respectively) and intrahepatic metastasis (P < 0.001 and P = 0.019, respectively). Importantly, Kaplan–Meier survival analysis showed that the disease-specific survival (DSS) and recurrence-free survival (RFS) were lower in CL with high PKM2 expression than in NCL with high PKM2 expression (P = 0.003 and P = 0.003, respectively). Overall, high PKM2 expression was more frequently found in CL than in NCL, and PKM2 overexpression was associated with poor survival rates in patients with CL and NCL.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common human cancer and represents the third most frequent cause of cancer deaths worldwide, with an estimated 745 000 deaths occurring annually[1,2,3]
We used western bloting to examine the expressions of pyruvate kinase M2 (PKM2) in each of 9 paired tumorous liver tissues and adjacent non-tumorous liver tissues in cirrhotic HCC and non-cirrhotic HCC
We found a large number of fibre strands between HCC cells in cirrhotic HCC (Fig. 2A), and the expression of PKM2 was mainly concentrated in the cytoplasm (Fig. 2B)

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common human cancer and represents the third most frequent cause of cancer deaths worldwide, with an estimated 745 000 deaths occurring annually[1,2,3]. The majority of HCC patients often have liver cirrhosis, and the liver cirrhosis is caused by multiple internal and external factors, including alcohol consumption, hepatitis viruses, and fatty liver disease[5]. There is increasing evidence that PKM2 is involved in nutritional and metabolic neoplastic disease, but the associations among the protein expression level of PKM2, clinical significance, and the survival rate of HCC patients with cirrhosis or non-cirrhosis is unclear. We investigated the expression level of PKM2 in HCC with cirrhosis or non-cirrhosis and in paracancerous tissues. We tried to find the influence of PKM2 expression the on the development of HCC with cirrhosis or non-cirrhosis and explored the possibility that PKM2 is a prognostic factors in HCC, and at the same time, we attempted to provide a reliable basis for scientific personalized treatment of HCC

Methods

Results

Conclusion