Elevated PHD2 expression might serve as a valuable biomarker of poor prognosis in lung adenocarcinoma, but no lung squamous cell carcinoma.

Abstract

Using data from The Cancer Genome Atlas (TCGA), we aimed to explore the association between Egl nine homolog 1 (EGLN1/PHD2) expression and survival outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. A retrospective study was conducted based on the level-3 data in the Cancer Genome Atlas (TCGA)-LUAD and TCGA-LUSC and data from the Human Protein Atlas (HPA). Both LUAD and LUSC had elevated PHD2 expression compared to their respective adjacent normal tissues. However, Kaplan-Meier survival curves showed that the high PHD2 expression LUAD patients had a significantly shorter overall survival (OS) and recurrence-free survival (RFS) (p=0.001 and p<0.001) compared to the low expression group. However, these differences were not observed in LUSC patients. Univariate and multivariate analysis showed that high PHD2 expression was an independent indicator of unfavorable OS (HR: 1.685, 95%CI: 1.251-2.269, p=0.001) and unfavorable RFS (HR: 2.008, 95%CI: 1.430-2.818, p<0.001) in LUAD patients. The methylation status of two CpG sites (cg07040244 and cg21875980) in PHD2 was at least moderately and negatively correlated with PHD2 expression. High methylation level of these two CpG sites was associated with better OS in LUAD patients. Elevated PHD2 expression might only serve as a valuable biomarker of poor prognosis in LUAD, but no in LUSC. Cg07040244 and cg21875980 might be two CpG sites modulating PHD2 expression in LUAD.