Abstract
BackgroundClinical 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.MethodsWe 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.ResultsTwelve 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).ConclusionERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data.
Highlights
Clinical options for lung squamous carcinoma (LUSC) are still quite limited
Some found that the nuclear ERβ predicted a better prognosis, and the expression level of cytoplasm was associated with a poor prognosis [12,13,14,15]
Differentially expressed genes (DEGs) were identified with paired t test, composed of 6416 up-regulated genes and 6338 down-regulated genes (Fig. 2A)
Summary
Clinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Estrogen is believed to play an important role in lung carcinogenesis [10, 11]. Some studies showed that ERα in lung cancer was mainly observed in the cytoplasm and associated with a poor prognosis. The majority of these researches focused on female patients [20,21,22], probably subjected to the stereotypical thinking that estrogen plays a more important role in women. According to literature review, ER-related investigations in lung cancer were majorly concentrating upon adenocarcinoma, seldom paying enough attention to LUSC, except for some subgroup analyses among NSCLC, let alone male LUSC patients. The relationship between ER and the prognosis of male LUSC is greatly needed in order to provide a potential therapeutic target for these patients, since the majority of the LUSC patients are male
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