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

Abstract

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 I² 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.

Keywords: Lung squamous cell carcinoma; Meta-analysis; PDPN protein; Prognosis; Stem cell marker.

Fig. 1

Literature search strategy and selection of articles

Fig. 2

Forest plot depiction of podoplanin expression and OR for clinical pathologic features. Clinicopathological parameters investigated are TMN classification (a), lymphatic invasion (b), vascular invasion (c), pleural metastasis (d), lymph node metastasis (e), sex (f). OR with corresponding confidence intervals are shown

Fig. 3

Analysis of podoplanin expression and survival of LUSC patients. Forest plot of HR for OS (a), OS (after deletion of Juan Li study) (b) and PFS (c) among included studies

Fig. 4

Begg’s funnel plot estimated the publication bias of the included literature for OS (a) and DFS (b)