Podoplanin is a useful prognostic marker and indicates better differentiation in lung squamous cell cancer patients? A systematic review and meta-analysis

BACKGROUND: The CSC (cancer stem cell) markers often indicate poor prognosis and more cell invasion or migration of cancer patients. Podoplanin was assumed as a candidate CSC marker and predict poor prognosis among squamous cancers. Whereas, the prognostic value of podoplanin among lung squamous cancer (LUSC) patients remains controversial. METHODS: A search of databases including PubMed, Embase and Web of Science was performed. Eligible articles studying the prognostic significance of podoplanin were selected. Odds ratio and HR (hazard ratio) were used to assess the relationships between podoplanin and clinical characteristics, as well as to quantify its prognostic role. The heterogeneity was estimated by I(2) Statistic and P values from sensitivity analysis. Begg’s funnel plots were used to estimate possible publication bias. RESULTS: 8 eligible studies containing 725 I-IV LUSC patients were included. Podoplanin expression showed no significant correlations with TNM stage, vascular invasion, lymphatic invasion, lymph node metastasis, pleural metastasis of tumor and gender of patients. However, podoplanin showed significant associations with better differentiation (pooled OR = 2.64, 95% CI 1.53–4.56, P = 0.0005, fixed effect) and better overall survival (HR = 2.14, 95% CI 1.45–3.15, P = 0.0001, fixed effect) and progression-free survival (HR = 1.73, 95% CI: 1.01–2.98, P = 0.05, fixed effect) of LUSC. Funnel plots illustrated no evidence of publication bias in our results. CONCLUSIONS: Podoplanin could be a useful prognostic marker and indicates better differentiation for LUSC patients, and the value of PDPN expression as a marker for cancer stem cells in LUSC should be critically evaluated in future studies.