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Expression of pyruvate kinase M2 in human bladder cancer and its correlation with clinical parameters and prognosis

Authors Huang CK, Huang ZC, Bai PM, Luo GC, Zhao XK, Wang XJ

Received 1 October 2017

Accepted for publication 14 February 2018

Published 11 April 2018 Volume 2018:11 Pages 2075—2082

DOI https://doi.org/10.2147/OTT.S152999

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Changkun Huang,1,* Zhichao Huang,1,* Peiming Bai,2 Guangcheng Luo,2 Xiaokun Zhao,1 Xinjun Wang2

1Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Xiamen University, Xiamen, People’s Republic of China

*These authors contributed equally to this work

Background: Pyruvate kinase M2 (PKM2) is a key regulator of the Warburg effect and has critical functions in glycolysis, contributing to the Warburg effect, tumor growth, angiogenesis, cell division, metastasis, and apoptosis. The high expression of PKM2 in various solid tumors renders it a potential biomarker of tumorigenesis and tumor invasion, but the expression and role of PKM2 in bladder cancer have not been studied extensively.
Patients and methods: Western blot and immunohistochemistry (IHC) were used to measure the expression of PKM2, and quantitative real-time polymerase chain reaction (PCR) was performed to determine PKM2 mRNA levels. The relationships between PKM2 expression and clinicopathological parameters and prognosis were analyzed using the Kaplan–Meier plots and a Cox proportional hazards regression model.
Results: Compared with paired adjacent normal bladder tissues, PKM2 mRNA and protein levels were found to be higher in urothelial carcinoma of the bladder (UCB) samples by real-time PCR and Western blot. By IHC, high expression of PKM2 was seen in 117 of 215 UCBs (54.4%) and in eight of 90 adjacent normal bladder tissues (8.9%). The expression of PKM2 was significantly associated with grade, stage, and lymph node status (P<0.001). In the univariate survival analysis, a significant association between PKM2 expression and shorter patient survival was observed (P<0.001). In different subsets of UCB patients, we found that PKM2 expression was a prognostic factor in patients with G2 (P=0.009), G3 (P<0.001), pTa/pTis (P=0.006), pT1, pT2–4, and pN- disease (P<0.001). Importantly, PKM2 expression (P=0.003), with tumor histological grade (P<0.001), pT (P<0.001), and pN status (P=0.005), was a significant independent prognostic parameter in the multivariate analysis.
Conclusion:
PKM2 protein and mRNA are upregulated in UCBs and may serve as molecular markers for a poor prognosis in patients with UCB.

Keywords:
bladder, urothelial carcinoma, PKM2, prognosis, IHC

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