PHLPP2 as a novel metastatic and prognostic biomarker in non-small cell lung cancer patients

Abstract

Background: PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) has been reported to be a potent tumor suppressor in many human cancers. However, PHLPP2 has not been fully researched as a putative clinical prognostic biomarker of lung cancer. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases including data on 1383 non-small cell lung cancer (NSCLC) patients were used to determine PHLPP2 expression. PHLPP2 expression was then examined by immunohistochemistry, and its clinical significance analyzed in 134 NSCLC patients, including 73 patients with adenocarcinoma and 81 with squamous cell carcinoma. Results: We found PHLPP2 expression to be less pronounced in NSCLC tissue samples than that in nontumoral lung tissues according to data taken from TCGA and GEO datasets; this outcome was further validated by immunohistochemistry assay. The low PHLPP2 expression level was found to be associated with the presence of lymph node metastasis (P = 0.003). Importantly, PHLPP2 was found to be an independent indicator of prognosis for overall (hazard ratio [HR] = 0.520, 95% confidence interval [Cl] = 0.327–0.827; P = 0.006) and disease-free survival (HR = 0.489, 95% Cl = 0.308–0.775; P = 0.002) in patients with surgically-resected NSCLC by multivariate analysis. Conclusion: Taken together, our findings show that PHLPP2 is a robust clinical marker for NSCLC survival and could serve as a potential therapeutic target.