CONUT was a convenient and useful tool to assess nutritional status before esophagectomy. Patients with moderate or severe malnutrition according to CONUT are at high risk for postoperative complications.
Purpose: PIK3CA encodes the catalytic subunit of PI3K, p110a. Mutant PIK3CA stimulates the AKT pathway and promotes cancer cell proliferation. PIK3CA mutations have been associated with poor prognosis in patients with colorectal or lung cancer. In contrast, the relationship between PIK3CA mutations and favorable prognoses has been shown in breast cancer. However, the influence of PIK3CA mutations on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains unclear.Experimental Design: Using a nonbiased database of 219 curatively resected ESCCs and eight esophageal cancer cell lines, we evaluated PIK3CA mutational status by pyrosequencing. The expression of p53 and phosphorylated AKT (i.e., AKT activation) was evaluated by immunohistochemistry.Results: PIK3CA mutations in exon 9 and/or 20 were detected in 46 cases (21%). No ESCC cell line harbored PIK3CA mutations. PIK3CA mutations were significantly associated with phosphorylated AKT expression, but not with p53 expression, sex, age at surgery, tobacco use, alcohol use, or histologic grade. Compared with wild-type PIK3CA cases, patients with PIK3CA mutations in exons 9 and/or 20 experienced significantly better disease-free survival [log-rank P ¼ 0.0089; univariate HR: 0.37, 95% confidence interval (CI): 0.15-0.75, P ¼ 0.0042; multivariate HR: 0.34, 95% CI: 0.10-0.86, P ¼ 0.021] and overall survival (log-rank P ¼ 0.012; univariate HR: 0.38, 95% CI: 0.16-0.78, P ¼ 0.0060; multivariate HR: 0.35, 95% CI: 0.10-0.90, P ¼ 0.028).Conclusion: PIK3CA mutations in ESCC are associated with longer survival, suggesting its role as a prognostic biomarker. Future studies are needed to confirm this association and to elucidate the exact mechanisms by which PIK3CA mutations affect tumor behavior.
BackgroundGenome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear.MethodsUsing 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables.ResultsGastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p < 0.0001; n = 74). Tumoral LINE-1 methylation range was 11.6–97.5 on a 0–100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09–3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02–3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04–4.04, p = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25).ConclusionsLINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker.
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