Abstract
BackgroundTo examine the clinical value of miR-198-5p in lung squamous cell carcinoma (LUSC).MethodsGene Expression Omnibus (GEO) microarray datasets were used to explore the miR-198-5p expression and its diagnostic value in LUSC. Real-time reverse transcription quantitative polymerase chain reaction was used to evaluate the expression of miR-198-5p in 23 formalin-fixed, paraffin-embedded (FFPE) LUSC tissues and corresponding non-cancerous tissues. The correlation between miR-198-5p expression and clinic pathological features was assessed. Meanwhile, putative target messenger RNAs of miR-198-5p were identified based on the analysis of differentially expressed genes in the Cancer Genome Atlas (TCGA) and 12 miRNA prediction tools. Subsequently, the putative target genes were sent to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses.ResultsMiR-198-5p was low expressed in LUSC tissues. The combined standard mean difference (SMD) values of miR-198-5p expression based on GEO datasets were − 0.30 (95% confidence interval (CI) − 0.54, − 0.06) and − 0.39 (95% CI − 0.83, 0.05) using fixed effect model and random effect model, respectively. The sensitivity and specificity were not sufficiently high, as the area under the curve (AUC) was 0.7749 (Q* = 0.7143) based on summarized receiver operating characteristic (SROC) curves constructed using GEO datasets. Based on the in-house RT-qPCR, miR-198-5p expression was 4.3826 ± 1.7660 in LUSC tissues and 4.4522 ± 1.8263 in adjacent normal tissues (P = 0.885). The expression of miR-198-5p was significantly higher in patients with early TNM stages (I-II) than that in cases with advanced TNM stages (III-IV) (5.4400 ± 1.5277 vs 3.5690 ± 1.5228, P = 0.008). Continuous variable-based meta-analysis of GEO and PCR data displayed the SMD values of − 0.26 (95% CI − 0.48, − 0.04) and − 0.34 (95% CI − 0.71, 0.04) based on fixed and random effect models, respectively. As for the diagnostic value of miR-198-5p, the AUC based on the SROC curve using GEO and PCR data was 0.7351 (Q* = 0.6812). In total, 542 genes were identified as the targets of miR-198-5p. The most enriched Gene Ontology terms were epidermis development among biological processes, cell junction among cellular components, and protein dimerization activity among molecule functions. The pathway of non-small cell lung cancer was the most significant pathway identified using Kyoto Encyclopedia of Genes and Genomes analysis.ConclusionThe expression of miR-198-5p is related to the TNM stage. Thus, miR-198-5p might play an important role via its target genes in LUSC.
Highlights
To examine the clinical value of miR-198-5p in lung squamous cell carcinoma (LUSC)
To evaluate the clinical significance of miR-198-5p in LUSC, we examined miR-198-5p expression in LUSC tissues and carried out additional specific analyses to uncover its clinicopathological role
Considering the meta-analysis of miR-198-5p expressionbased Gene Expression Omnibus (GEO) data, eight datasets were included in our study
Summary
To examine the clinical value of miR-198-5p in lung squamous cell carcinoma (LUSC). Non-small cell lung cancer (NSCLC) accounts for around 85% of all lung cancers, with 30% of NSCLC cases being classified as lung squamous cell carcinoma (LUSC) [2,3,4,5,6,7]. MicroRNAs (miRNAs) are ∼ 22-nt long endogenous RNAs that play significant roles in various cellular processes [9]. Previous studies have shown that miRNAs can target mRNAs involved in most of the developmental processes and are associating with many diseases [10]. Studies have found that miR198-5p plays a vital role in many human cancers, including lung cancer [12]. The relationship between miR-198-5p and lung squamous cell carcinoma as well as the underlying mechanism remains unknown
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