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

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.

Next-generation sequencing revealed synchronous double primary lung squamous carcinoma: a case report

Synchronous double primary lung squamous carcinoma (sDPLSCC) is rare and difficult to distinguish from metastatic disease, histopathologically. Owing to the heterogeneity of cancer, it is also difficult to select the optimal therapeutic strategy for patients with multiple primary lung cancer (MPLC). The present study reports a rare case of a 61-year-old male patient with sDPLSCC diagnosed using histology and genetic profiling. LSCC-related driver mutations were detected in this patient, and we reported the TP53 c.475G>C mutation, which has been detected in both breast cancer and hepatocellular carcinoma, but not previously in lung squamous carcinoma. Our findings provide further evidence supporting the necessity of genetic testing for primary tumor diagnosis.

The positive RNASEH1-AS1/has-miR-218-5p/NET1 feedback loop mediated by POU2F1 contributes to the development and progression of human lung squamous carcinoma

Background At the molecular level, competing endogenous RNAs (ceRNAs) regulate other RNA transcripts by competing for shared microRNAs (miRNA). Notably, miRNAs negatively regulate gene expression at the levels of mRNA stability and translation suppression.MethodsWe measured theexpression of miR-218-5p and RNASEH1-AS1 in clinical lung squamous cell carcinoma tissues using qRT-PCR. In an attempt to explore the roles of miR-218-5p and RNASEH1-AS1 in determining the malignant phenotype of NCI-H520 cells, colony formation and MTT assays were performed to measure cell viability and proliferation, and transwell invasion and wound healing assays were performed to examine cell migration and invasion. A ChIP assay was conducted to confirm the direct binding of POU2F1 to the RNASEH1-AS1 promoter.ResultsIn this investigation, the expression of the lncRNA RNASEH1-AS1 is upregulated in human lung cancer tissues, and it functions as a miRNA sponge for hsa-miR-218-5p in human lung squamous carcinoma cells. The lncRNA RNASEH1-AS1 facilitates the growth and motility of lung squamous carcinoma cells, while miR-218-5p exerts the opposite effects. NET1 and POU2F1 are validated as direct and functional targets of miR-218-5p. The downregulation of miR-218-5p releases the suppression of NET1 and POU2F1. POU2F1 binds directly to the lncRNA-RNASEH1-AS1 promoter and functions as transcription factor to enhance the promoter activity of RNASEH1-AS1.ConclusionsOverall, the positive RNASEH1-AS1/hsa-miR-218-5p/NET1/POU2F1 feedback loop can help us understand the regulatory mechanism underlying the genesis and progression of human lung squamouscarcinoma, possibly providing new biomarkers for its diagnosis and treatment.

Identification of Potential Long Non-coding RNA Expression Quantitative Trait Methylations in Lung Adenocarcinoma and Lung Squamous Carcinoma

There are associations between DNA methylation and the expression of long non-coding RNA (lncRNA), also known as lncRNA expression quantitative trait methylations (lnc-eQTMs). Lnc-eQTMs may induce a wide range of carcinogenesis pathways. However, lnc-eQTMs have not been globally identified and studied, and their roles in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) are largely unknown. In the present study, we identified some differential methylation sites located in genes of long intergenic non-coding RNAs (lincRNAs) and other types of lncRNAs in LUAD and LUSC. An integrated pipeline was established to construct two global cancer-specific regulatory networks of lnc-eQTMs in LUAD and LUSC. The associations between eQTMs showed common and specific features between LUAD and LUSC. Some lnc-eQTMs were also related with survival in LUAD- and LUSC-specific regulatory networks. Lnc-eQTMs were associated with cancer-related functions, such as lung epithelium development and vasculogenesis by functional analysis. Drug repurposing analysis revealed that these lnc-eQTMs may mediate the effects of some anesthesia-related drugs in LUAD and LUSC. In summary, the present study elucidates the roles of lnc-eQTMs in LUAD and LUSC, which could improve our understanding of lung cancer pathogenesis and facilitate treatment.