Impact Factor 4.137 | CiteScore 4.28
More on impact ›

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01123

Prognostic impact of metabolism reprogramming markers acetyl-CoA synthetase 2 phosphorylation and ketohexokinase-A expression in non-small-cell lung carcinoma

Xueying Yang1, Fei Shao1, Susheng Shi1, Xiaoli Feng1, Wei Wang1, Yalong Wang1, Wei Guo1, juhong Wang1, Shugeng Gao1,  Yibo Gao1*, Zhimin Lu2* and  Jie He1*
  • 1Chinese Academy of Medical Sciences and Peking Union Medical College, China
  • 2Institute of Translational Medicine, Zhejiang University School of Medicine, China

Background. The identification of prognostic markers for non-small-cell lung carcinoma (NSCLC) is needed for clinical practice. The metabolism-reprogramming marker ketohexokinase (KHK)-A and acetyl-CoA synthetase 2 (ACSS2) phosphorylation at S659 (ACSS2 pS659) play important roles in tumorigenesis and tumor development. However, the clinical significance of KHK-A and ACSS2 pS659 in NSCLC is largely unknown.
Methods. The expression levels of KHK-A and ACSS2 pS659 were assessed by immunohistochemistry analyses of surgical specimens from 303 NSCLC patients. The prognostic values of KHK-A and ACSS2 pS659 were evaluated by Kaplan-Meier methods and Cox regression models.
Results. The expression levels of KHK-A and ACSS2 pS659 were significantly higher in NSCLC tissues than those in adjacent non-tumor tissues (P<0.0001). KHK-A or ACSS2 pS659 alone and the combination of KHK-A and ACSS2 pS659 were inversely correlated with overall survival in NSCLC patients (P<0.001). The multivariate analysis indicated that KHK-A or ACSS2 pS659 and KHK-A/ACSS2 pS659 were independent prognostic biomarkers for NSCLC (P=0.008 for KHK-A, P<0.001 for ACSS2 pS659, and P<0.001 for KHK-A/ACSS2 pS659). Furthermore, the combination of KHK-A and ACSS2 pS659 can be used as a prognostic indicator for all stages of NSCLC.
Conclusions. KHK-A or ACSS2 pS659 alone and the combination of KHK-A and ACSS2 pS659 can be used as prognostic markers for NSCLC. Our findings highlight the important role of metabolic reprogramming in NSCLC progression.

Keywords: metabolism reprogramming, KHK-A, ACSS2 pS659, non-small-cell lung carcinoma, prognosis, Immunohistochemistry

Received: 19 Jul 2019; Accepted: 09 Oct 2019.

Copyright: © 2019 Yang, Shao, Shi, Feng, Wang, Wang, Guo, Wang, Gao, Gao, Lu and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Yibo Gao, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100006, Beijing Municipality, China, gaoyibo@cicams.ac.cn
Dr. Zhimin Lu, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, China, zhiminlu@zju.edu.cn
Dr. Jie He, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100006, Beijing Municipality, China, prof.jiehe@gmail.com