AUTHOR=Yang Xueying , Shao Fei , Shi Susheng , Feng Xiaoli , Wang Wei , Wang Yalong , Guo Wei , Wang Juhong , Gao Shugeng , Gao Yibo , Lu Zhimin , He Jie
TITLE=Prognostic Impact of Metabolism Reprogramming Markers Acetyl-CoA Synthetase 2 Phosphorylation and Ketohexokinase-A Expression in Non-Small-Cell Lung Carcinoma
JOURNAL=Frontiers in Oncology
VOLUME=9
YEAR=2019
URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01123
DOI=10.3389/fonc.2019.01123
ISSN=2234-943X
ABSTRACT=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.