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.