Identification of a seven-miRNA signature as prognostic biomarker for lung squamous cell carcinoma

Gao, Xiujuan; Wu, Yupeng; Yu, Wenwen; Li, Hui

doi:10.18632/oncotarget.13164

Cited by 36 publications

(29 citation statements)

References 49 publications

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“…MiRNAs are important in the occurrence and development of LC [43][44][45][46][47][48]. Recent studies reported that dysregulation of the expression of multiple miRNAs, including miR-182-5p, was significantly correlated with tumorigenesis of LC [34].…”

Section: Discussionmentioning

confidence: 99%

MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip

Yan

Yang

et al. 2020

BMC Med Genomics

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Background: MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC). Methods: The clinical significance of miR-182-5p in NSCLC subtypes was determined based on an analysis of 124 samples (lung adenocarcinomas [LUADs], n = 101; lung squamous cell carcinomas [LUSCs], n = 23) obtained from NSCLC patients and paired noncancer tissues and an analysis of data obtained from public miRNA-seq database, miRNA-chip database, and the scientific literature. The NSCLC samples (n = 124) were analyzed using the real-time quantitative polymerase chain reaction (RT-qPCR). Potential targets of miR-182-5p were identified using lists generated by miRWalk v.2.0, a comprehensive atlas of predicted and validated targets of miRNA-target interactions. Molecular events of miR-182-5p in NSCLC were unveiled based on a functional analysis of candidate targets. The association of miR-182-5p with one of the candidate target genes, homeobox A9 (HOXA9), was validated using inhouse RT-qPCR and dual-luciferase reporter assays. Results: The results of the in-house RT-qPCR assays analysis of data obtained from public miRNA-seq databases, miRNA-chip databases, and the scientific literature all supported upregulation of the expression level of miR-182-5p level in NSCLC. Moreover, the in-house RT-qPCR data supported the influence of upregulated miR-182-5p on malignant progression of NSCLC. In total, 774 prospective targets of miR-182-5p were identified. These targets were mainly clustered in pathways associated with biological processes, such as axonogenesis, axonal development, and Ras protein signal transduction, as well as pathways involved in axonal guidance, melanogenesis, and longevity regulation, in multiple species. Correlation analysis of the in-house RT-qPCR data and dual-luciferase reporter assays confirmed that HOXA9 was a direct target of miR-182-5p in NSCLC. Conclusions: The miR-182-5p expression level was upregulated in NSCLC tissues. MiR-182-5p may exert oncogenic influence on NSCLC through regulating target genes such as HOXA9.

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Section: Discussionmentioning

confidence: 99%

MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip

Yan

Yang

et al. 2020

BMC Med Genomics

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“…Yu et al [ 18 ] investigated whether microRNA expression profiles can predict clinical outcome of NSCLC patients using real-time RT-PCR and identified a five-microRNA signature for the prediction of treatment outcome of NSCLC, which is an independent predictor of the cancer relapse and survival of NSCLC patients. Recently, Gao et al [ 19 ] reported that seven-miRNA signature may have clinical implications in the outcome prediction of lung squamous cell carcinoma (LUSC). Of these 7 miRNAs, 2 (hsa-mir-139, hsa-mir-326) were negatively correlated with survival, while the other 5 (miR-101-2, miR-182, miR-183, miR-190, hsa-miR-944) were protective.…”

Section: Discussionmentioning

confidence: 99%

High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1

Zhu

Kong

et al. 2017

Oncotarget

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Increasing evidence supports that microRNA (miRNA)-mediated gene regulation plays a significant functional role in cancer progression. To investigate the expression and clinical significance of ITGB1 in non small cell lung cancer (NSCLC), the expression levels of ITGB1 in NSCLC tissues and human normal lung tissues were analyzed in silico using genes microarray, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results showed that ITGB1 was upregulated in NSCLC tissues when compared with normal lung tissues. Survival analysis based on the qRT-PCR data established that ITGB1 expression was attentively related to the prognosis of NSCLC, and patients with higher ITGB1 expression had shorter overall survival (OS). Moreover, ITGB1 was confirmed to be a direct target of miR-493-5p. Furthermore, concomitant high expression of ITGB1 and low expression of miR-493-5p correlated with a shorter median OS and PFS in NSCLC patients. In conclusion, our results provide the first evidence that ITGB1 is a direct target of miR-493-5p suggesting that ITGB1 and miR-493-5p may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of NSCLC patients.

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“…However, the mechanism of LUSC is complex, and the prognosis of LUSC cannot be adequately explained by a single gene. In addition, although, in several studies, more than one gene was identified, the signatures were diverse. This has resulted in application difficulties and challenges in clinical practice because selecting the best signature is not an easy task.…”

Section: Introductionmentioning

confidence: 99%

Identification of 17 mRNAs and a miRNA as an integrated prognostic signature for lung squamous cell carcinoma

Zhang

Bing

Yan

et al. 2019

The Journal of Gene Medicine

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Background Gene signatures for predicting the outcome of lung squamous cell carcinoma (LUSC) have been employed for many years. However, various signatures have been applied in clinical practice. Therefore, in the present study, we aimed to filter out an effective LUSC prognostic gene signature by simultaneously integrating mRNA and microRNA (miRNA). Methods First, based on data from the Cancer Genome Atlas (TCGA) (https://www.cancer.gov/tcga), mRNAs and miRNAs that were related to overall survival of LUSC were obtained by the least absolute shrinkage and selection operator method. Subsequently, the predicting effect was tested by time‐dependent receiver operating characteristic curve analysis and Kaplan–Meier survival analysis. Next, related clinical indices were added to evaluate the efficiency of the selected gene signatures. Finally, validation and comparison using three independent gene signatures were performed using data from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo). Results Our data showed that the prognostic index (PI) contained 17 mRNAs and one miRNA. According to the best normalized cut‐off of PI (0.0247), the hazard ratio of the PI was 3.40 (95% confidence interval = 2.33–4.96). Moreover, when clinical factors were introduced, the PI was still the most significant index. In addition, only two Gene Ontology terms with p < 0.05 were reported. Furthermore, validation implied that, using our 18‐gene signature, only hazard ratio = 1.36 (95% confidence interval = 1.01–1.83) was significant compared to the other three groups of gene biomarkers. Conclusions The 18‐gene signature selected based on data from the TCGA database had an effective prognostic value for LUSC patients.

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Identification of a seven-miRNA signature as prognostic biomarker for lung squamous cell carcinoma

Cited by 36 publications

References 49 publications

MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip

MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip

High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1

Identification of 17 mRNAs and a miRNA as an integrated prognostic signature for lung squamous cell carcinoma

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