Abstract
The lung cancer cells express genes involved in key points of the lung development. The objective of this study was to determine the prognostic value of expression of embryonic markers in tumor tissue samples from patients with surgically-treated non-small cell lung cancer (NSCLC). Study based on 129 primary tumor samples from 102 patients with surgically-treated NSCLC (99% R0) and 27 lung samples. Expression of the following markers was evaluated by mRNA RT-qPCR assay: CEACAM5, FGFR2b, FRS2, MYCN, SFTPC, SHH, SHP2, and SOX17 in the tumor and lung samples. Statistical analyses included chi-squared tests, non-parametric tests, Kaplan Meier curves, log-rank and Cox regression tests. Patients' characteristics were: mean age 67 ± 8 years, squamous carcinoma (49%), adenocarcinoma (43%), pathological staging: I: 56%, II: 32%, III: 11% and IV: 1%. 18% received adjuvant chemotherapy, 1% radiotherapy and 7% both. CEACAM5 and MYCN were overexpressed in tumor samples related to lung samples (p<0,05), FGFR2b showed similar expression and FRS2, SFTPC, SHH, SHP2 and SOX17 were underexpressed (p<0,05). The squamous carcinomas expressed more FGFR2b, FRS2 and SFTPC (p<0,10), while adenocarcinomas expressed more CEACAM5 (p>0,05). Lymph node involvement was associated with SHH underexpression (p<0,05), intratumoral vascular invasion with CEACAM5 or FGFR2b underexpression (p<0,05) and relapse with SHH (p<0,05) or SFTPC (p=0,09) underexpression. Kaplan-Meier curves of SFTPC were plotted in figure 1. Underexpression of SFTPC in the tumor sample was associated with a 7-fold (7.3; 1.3-40.9) greater active risk of recurrence and a nearly 5-fold (4.9; 1.04-23.2) greater risk of death. Underexpression of SHP2 was associated with a shorter disease-free survival interval (DFS) and overall survival (OS) (p=0.055). Overexpression of FGFR2b or SHH was associated with longer DFS and OS (p<0.05; for SHH, p=0.07 for OS). Combining markers did not provide any additional information. Underexpression of SFTPC in tumor samples was independently associated with worse prognosis.
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