Non-small cell lung cancer associated microRNA expression signature: integrated bioinformatics analysis, validation and clinical significance

Abstract

Recently, increasing studies of miRNA expression profiling has confirmed that miRNA plays an essential role in non-small cell lung cancer (NSCLC). However, inconsistent or discrepant results exist in these researches. In present study, we performed an integrative analysis of 32 miRNA profiling studies compared the differentially expressed miRNA between NSCLC tissue and non-cancerous lung tissue to identify candidate miRNAs associated with NSCLC. 7 upregulated and 10 downregulated miRNAs were identified as miRNA integrated-signature using Robust Rank Aggregation (RRA) method. qRT-PCR demonstrated that miR-21-5p, miR-210, miR-205-5p, miR-182-5p, miR-31-5p, miR-183-5p and miR-96-5p were up-regulated, whereas miR-126-3p, miR-30a-5p, miR-451a, miR-143-3p and miR-30d-5p were down-regulated more than 2 folds in the NSCLC, which was further validated in Tumor Cancer Genome Atlas (TCGA) database. Receiver operating characteristic (ROC) curve analysis confirmed that 9 miRNAs had good predictive performance (AUC > 0.9). Cox regression analysis revealed that miR-21-5p (hazard ratio [HR]: 1.616, 95% CI: 1.114–2.342, p = 0.011) and miR-30d-5p (HR: 0.578, 95% CI: 0.400–0.835, p = 0.003) were independent prognostic factors in NSCLC for overall survival. The accumulative effects of the two miRNAs on the prognosis of NSCLC were further estimated. The results showed that patients with two positive markers had a worse prognosis than those with one or none positive marker. In conclusion, this study contributes to the comprehension of the role of miRNAs in NSCLC and provides a basis for further clinical application.

Clinical Significance of miR-210 and its Prospective Signaling Pathways in Non-Small Cell Lung Cancer: Evidence from Gene Expression Omnibus and the Cancer Genome Atlas Data Mining with 2763 Samples and Validation via Real-Time Quantitative PCR

“…A microarray profile and real-time qPCR analysis confirmed the outcome of patients in a large cohort study by Donnem et al, and demonstrated that miR-210 was up-regulated (fold change = 1.74) and possibly associated with angiogenesis in NSCLC [61]. A series of microarray profile-based meta-analyses, which were published in 2012, 2013, and 2017, also came to the same conclusion that miR-210, along with several other miRNAs, was overexpressed in NSCLC [62-64]. In addition, the results of the present original estimation and meta-analysis results indicate that miR-210 was elevated in NSCLC, in agreement with the abovementioned studies.…”

“…miR-210 is aberrantly expressed in several cancers, such as malignant melanoma [13], pancreatic tumors [14], mammary cancer [15], and kidney carcinomas [16]. Several studies have reported the up-regulation of miR-210 expression using multiple microarrays [17-19]. In addition, a meta-analysis revealed the potential diagnostic capacity of miR-210 in NSCLC patients by detecting its expression level in blood and sputum [20].…”

Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer

“…This was used to identify DEGs and to rank them consistently and reliably without the influence of noise using R (8). This approach allowed an improved understanding of the molecular mechanisms involved in cancer (21). Meanwhile, the heatmap package [version 1.0.12 (22)] was used to generate the heatmap of these DEGs.…”

Expression Signature and Role of miR-30d-5p in Non-Small Cell Lung Cancer: a Comprehensive Study Based on in Silico Analysis of Public Databases and in Vitro Experiments

“…After scanning the titles and abstracts, we excluded 1090 studies. Eventually, four suitable studies were included in the meta-analysis [39][40][41][42]. Basic information from the included studies is listed in Table 4.…”