Co-expression of podoplanin and fibroblast growth factor 1 predicts poor prognosis in patients with lung squamous cell carcinoma

Li,Juan; Chen,Han; Li,Xiaoqing; Wang,Linlin; Gao,Aiqin; Zhang,Pei; Lin,Wenli; Gao,Wei; Yang,Dong; Guo,Xiaosun; Liu,Jie; Dang,Qi; Sun,Yuping

doi:10.3892/mmr.2017.6830

Co-expression of podoplanin and fibroblast growth factor 1 predicts poor prognosis in patients with lung squamous cell carcinoma

Authors:
- Juan Li
- Han Chen
- Xiaoqing Li
- Linlin Wang
- Aiqin Gao
- Pei Zhang
- Wenli Lin
- Wei Gao
- Dong Yang
- Xiaosun Guo
- Jie Liu
- Qi Dang
- Yuping Sun
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Affiliations: Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong 250013, P.R. China, Soochow University College of Medicine, Suzhou, Jiangsu 215000, P.R. China, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, P.R. China, Department of Oncology, Nan Lou Division, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Pathology, Jinan Central Hospital, Shandong University, Jinan, Shandong 250013, P.R. China, Department of Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong 250013, P.R. China
Published online on: June 21, 2017 https://doi.org/10.3892/mmr.2017.6830
Pages: 1643-1652
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Podoplanin and fibroblast growth factor (FGF) 1 have been detected more frequently in lung squamous cell carcinoma (SQCC) compared with lung adenocarcinoma. Furthermore, it has been previous demonstrated that FGF1 is located on the edge of tumor nests in certain lung SQCC sections, which resembles the characteristic expression pattern of podoplanin. Podoplanin and FGF1 have roles in lymphangiogenesis and angiogenesis. Based on their consistently specific expression in lung SQCC and similar localization patterns, the present study aimed to investigate whether the expression of podoplanin in tumor cells is correlated with FGF1 expression in lung SQCC and whether their co‑expression has clinicopathological significance, particularly for lymphangiogenesis/angiogenesis. The correlation between podoplanin and FGF1 expression in tumor cells of 82 lung SQCC cases was investigated by immunohistochemical staining and the association between the co‑expression of podoplanin and FGF1, and clinicopathological factors such as microvessel density (MVD), was examined in these samples. In addition, the prognostic value of co‑expression of podoplanin and FGF1 in tumor cells was determined, and the regulation of FGF1 expression and angiogenesis by podoplanin was examined in vitro in a human lung SQCC cell line. Immunohistochemical analysis demonstrated that there was a significant correlation between podoplanin and FGF1 expression in lung SQCC tumor cells (R=0.591; P<0.0001). Co‑expression of podoplanin and FGF1 was significantly associated with larger primary tumor size, advanced TNM stage and higher intratumoral MVD. Survival analysis demonstrated that cases with podoplanin and FGF1 double‑positive staining had a significantly lower survival rate compared with cases with double‑negative staining. In vitro experiments revealed that podoplanin regulated FGF1 expression and affected tube formation of human umbilical vein endothelial cells. Combined, the results demonstrated that podoplanin was co‑expressed with FGF1 in lung SQCC and this co‑expression was correlated with poor prognosis.

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