In addition to age $60 years and advanced tumor status, we identified high expression of pACC as an independent prognostic marker in SCCHN patients with node-positive or advanced -stage disease, a finding that has not been previously reported. pAMPK expression was associated with increased survival in lung cancer patients, particularly in those with adenocarcinoma, indicating that pAMPK expression may be useful as a prognostic marker for lung cancer. In the current study, pAMPK expression was observed more often in patients with early-stage tumor status than in those with advanced tumor status, suggesting a loss of protection from the pAMPK pathway with disease progression. Although univariate analysis showed a trend of better survival in all SCCHN patients with positive pAMPK expression, pAMPK did not have an impact on OS in the multivariate analysis after adjusting for tumor status, age, tumor site, and other factors. ACC is an important downstream target of pAMPK. ACC is a key regulatory enzyme in fatty acid de novo biosynthesis and lipogenesis. ACC catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA, an intermediate of fatty acid synthesis. This activity of ACC is inhibited by its phosphorylation. In humans, there are 2 ACC isoforms: ACC1, which is mainly located in the cytosol, and ACC2, which is located mainly in mitochondria. ACC1 is expressed in all cell types but is enriched in lipogenic tissues. Knockout mice with homozygous mutant ACC12/2 are embryonic lethal, whereas ACC22/2 mice live well and gain less weight than their wild-type counterparts. Inhibition of ACC has been shown to have antitumor activity in various cancers. Several studies have shown that dephosphorylation of ACC1 at Ser 79 is prevented by its interaction with breast cancer PI-103 PI3K inhibitor protein 1, a DNA repair gene involved in maintaining genetic stability. This finding suggested that inactivation of ACC1 may be involved in BRCA1- mediated tumor suppression. Inhibition of ACC induced apoptosis in breast and prostate cancer cells, suggesting ACC is essential for cancer cell survival. In contrast to GDC-0199 previous in vitro and in vivo studies, our data indicated that inhibition of ACC did not have a protective effect in SCCHN patients.