MicroRNA Classifiers for Predicting Prognosis of Squamous Cell Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC), which is comprised mainly of adenocarcinoma and squamous cell carcinoma (SCC), is the cause of 80% of all lung cancer deaths in the United States. NSCLC is also associated with a high rate of relapse after clinical treatment and, therefore, requires robust prognostic markers to better manage therapy options. The aim of this study was to identify microRNA (miRNA) expression profiles in SCC of the lung that would better predict prognosis. Total RNA from 61 SCC samples and 10 matched normal lung samples was processed for small RNA species and profiled on MirVana miRNA Bioarrays (version 2, Ambion). We identified 15 miRNAs that were differentially expressed between normal lung and SCC, including members of the miR-17-92 cluster and its paralogues. We also identified miRNAs, including miR-155 and let-7, which had previously been shown to have prognostic value in adenocarcinoma. Based on cross-fold validation analyses, miR-146b alone was found to have the strongest prediction accuracy for stratifying prognostic groups at f78%. The miRNA signatures were superior in predicting overall survival than a previously described 50-gene prognostic signature. Whereas there was no overlap between the mRNAs targeted by the prognostic miRNAs and the 50-gene expression signature, there was a significant overlap in the corresponding biological pathways, including fibroblast growth factor and interleukin-6 signaling. Our data indicate that miRNAs may have greater clinical utility in predicting the prognosis of patients with squamous cell lung carcinomas than mRNA-based signatures.

miR‐515‐5p controls cancer cell migration through MARK 4 regulation

“…(A) Survival analysis of miR‐515‐5p from 195 lung adenocarcinoma samples from the TCGA . (B) Survival analysis of miR‐515‐p from 34 lung squamous cell carcinoma from the TCGA 18. (C) Survival analysis of miR‐515‐5p from 60 breast cancer samples from the Lyng Ditzel Breast Study ( GSE 37405).…”

MicroRNA-155 Expression has Prognostic Value in Patients with Non-small Cell Lung Cancer and Digestive System Carcinomas

“…Several studies have corroborated this finding in lung cancer and other malignant diseases including colorectal cancer, breast cancer, hepatocelluar carcinomas, pancreatic ductal adenocarcinomas and adult T-cell leukemia (Raponi et al, 2009;Greither et al, 2010;Shibuya et al, 2010;Chen et al, 2012;Han et al, 2012;Huang et al, 2012;Ishihara et al, 2012;Papaconstantinou et al, 2012); however, other reports provided insignificant or opposite evidences (Jung et al, 2009;Voortman et al, 2010;Donnem et al, 2011;Saito et al, 2011;Monsálvez et al, 2012;Shinmei et al, 2012). In order to investigate the precise association between miR-155 expression and the prognosis of patients, we combined the HRs extracted from the eligible data, and found that patients with high miR-155 expression were likely to have an unfavorable outcome.…”

“…Recent studies have showed that miR-155 gene is one of the miRNAs most consistently over-expressed in both hematopoietic malignancies and solid tumors, such as leukemia (O'Connell et al, 2008;Raponi et al, 2009), thyroid carcinoma (Nikiforova et al, 2008), breast cancer (Iorio et al, 2005;Greither et al, 2010), cervical cancer (Wang et al, 2008), colorectal cancer , pancreatic ductal adenocarcinoma (PDAC) (Lee et al, 2007;Szafranska et al, 2007), hepatocellular carcinoma (Han et al, 2012;Huang et al, 2012), and lung cancer (Yanaihara et al, 2006;Donnem et al, 2011). Therefore, overexpression miR-155 may be a general characteristic of cancer and be detected as a biomarker for cancer diagnosis and prognosis.…”

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…Several studies have shown that downregulated expression of let-7, one of the earliest discovered miRNAs, was associated with poor prognosis in lung cancer patients [170][171][172][173]. This association was later proposed to be due to the let-7-mediated inhibition of RAS, which is a critical oncogene that is involved in lung cancer development [174].…”