ER expression associates with poor prognosis in male lung squamous carcinoma after radical resection

Abstract

Background Clinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Therefore, only looking into one layer of genomic dysregulation is far from sufficient. Methods We identified differentially expressed genes with consistent upstream genetic or epigenetic dysregulations in LUSC. Random walk was adopted to identify genes significantly affected by upstream abnormalities. Expression differentiation and survival analysis were conducted for these significant genes, respectively. Prognostic power of selected gene was also tested in 102 male LUSC samples through immunohistochemistry assay. Results Twelve genes were successfully retrieved from biological network, including ERα (ESRS1), EGFR, AR, ATXN1, MAPK3, PRKACA, PRKCA, SMAD4, TP53, TRAF2, UBQLN4 and YWHAG, which were closely related to sex hormone signaling pathway. Survival analysis in public datasets indicated ERα was significantly associated with a poor overall survival (OS) in male LUSC. The result of our immunohistochemistry assay also demonstrated this correlation using R0 resected tumors (n = 102, HR: 2.152, 95% CI: 1.089–4.255, p = 0.024). Although disease-free survival (DFS) difference was non-significant (n = 102, p = 0.12), the tendency of distinction was straight-forward. Cox analysis indicated ERα was the only independent prognostic factor for male patients’ OS after R0 resection (HR = 2.152, p = 0.037). Conclusion ERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data.

ER predicts poor prognosis in male lung squamous cell cancer of stage IIIA-N2 disease after sequential adjuvant chemoradiotherapy

“…The remarkable controversy is probably due to many reasons, for instance, the patient population selected for research, the heterogeneous definitions of positivity, the differences in detecting methodology, and so on (14,15,34). Our previous finding indicated that the expression of ER predicted a poor clinical outcome in male LUSCs after receiving radical operation, which was also demonstrated by IHC assay (23). In present study, ER was significantly associated with DFS, OS, LRFS, and DMFS in male LUSCs after adjuvant sequential chemoradiotherapy.…”

“…The primary limitation of this study is the limited patient number (n=124), since we set a very strict enrollment criterion to reduce the potential bias. We only focused on male stage IIIA-N2 LUSCs with definitive molecular information of their EGFR and ALK status, and only patients strictly completed the sequential adjuvant chemoradiotherapy were enrolled, trying to validate the hypothesis inspired by our previous study (23). Additionally, this study is a single-center retrospective study.…”

“…LUSC patients are mainly male, and ER expression was reported as a significant unfavorable predictor of the clinical outcome in male LUSCs after radical resection in our previous study (23). In this study, we specifically focused on male stage IIIA-N2 LUSC who received sequential adjuvant chemotherapy and PORT, in attempt to establish the correlation between ER status and the prognosis of these patients.…”