Association of microRNA-33a Molecular Signature with Non-Small Cell Lung Cancer Diagnosis and Prognosis after Chemotherapy

Hou, Likun; Ma, Yu‐Shui; Han, Yang; Lu, Gai‐Xia; Luo, Pan; Chang, Zhengyan; Xie, Ruting; Yang, Haojie; Chai, Li; Cai, Meili; Wu, Ting‐Miao; Yu, Fei; Qin, Shanshan; Lv, Zhongwei; Wu, Chunyan; Fu, Da

doi:10.1371/journal.pone.0170431

Cited by 33 publications

(26 citation statements)

References 40 publications

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“…These affects are mainly due to the regulation of messenger RNA (mRNA) by miRNA . In addition, various types of miRNAs display different levels of expression in specific types of malignancies . Therefore, the mRNA and miRNA data of a patient with LUSC samples in the TCGA database were used to find new biomarkers in our study.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

Gao

Feng

et al. 2019

J of Cellular Biochemistry

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Background With the development in research, the importance of microRNAs (miRNAs) in the occurrence and metastasis, and prognosis of lung squamous cell carcinoma (LUSC) have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics. Materials and methods We downloaded miRNA and messenger RNA samples related to LUSC from The Cancer Genome Atlas (TCGA) database. Following initial data screening and preprocessing, we utilized the R platform and a range of analysis tools (miRDB, TargetScanHuman7.2, DAVID, and Cytoscape_v3.5.1) to analyze the TCGA data and identify highly specific and sensitive biomarkers. Results We finally identified 12 miRNAs and six central genes closely related to the overall survival of patients with LUSC. We found that high expression of 7 miRNAs (miR‐301b, miR‐383, miR‐512, miR‐515, miR‐525, miR‐577, and miR‐5682) and low expression of five miRNAs (miR‐448, miR‐486, miR‐4732,miR‐4732, miR‐516, and miR‐1911) can significantly improve the overall survival rate of patients with LUSC. The six central genes DLGAP5, CENPA, CHEK1, LRRK2, CALB1, and TOP2A are directly or indirectly involved in the formation and metastasis of LUSC and could, therefore, be considered as target genes for drug therapy. Conclusion With the development in research, the importance of miRNAs in the occurrence and metastasis and prognosis of LUSC have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics.

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Section: Introductionmentioning

confidence: 99%

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

Gao

Feng

et al. 2019

J of Cellular Biochemistry

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“…We obtained the highest AUC values (viz., 0.95 for SVM, 0.955 for RF, 0.955 for PAM) for our resultant gene signature estimated by our proposed method, De-MoS. On the other hand, for the gene signature obtained by Li et al (2017) [6], the corresponding AUC values across these three classifiers were 0.535 for SVM, 0.5625 for RF and 0.585 for PAM, whereas for the gene signature found by Li et al (2018) [28], those values were 0.535 for SVM, 0.5625 for RF and 0.585 for PAM. Another gene signature estimated by Huang et al (2011) [29], the AUC values for SVM, RF and PAM classifiers were 0.83, 0.66 and 0.75, respectively.…”

Section: Resultsmentioning

confidence: 67%

“…Gene signatures might be targeted by various miRNAs, which are non-coding RNAs (approximately 18-25 nucleotides long) that participate in the post-transcriptional regulation of gene expression [5]. These miRNAs are abnormally expressed in various malignancies as tumor suppressors or oncogenes [6]. They regulate various processes in carcinogenesis such as metastasis [7] and cell proliferation [8].…”

Section: Introductionmentioning

confidence: 99%

DeMoS: Dense Module based Gene Signature Detection through Quasi-Clique: An Application to Cervical Cancer Prognosis

Saha¹,

Mallik²,

Bandyopadhyay³

2020

Preprint

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Background: Gene signature is useful to represent the molecular alternation in the disease genomes at specified conditions and is often used to distinguish samples into various groups for better research prospective as well as better clinical treatment. There is lack of efficient techniques that can take into account the complex gene expression profile and able to identify the most relevant signatures. Methods: In this article, we presented a new framework to identify Dense Module based gene Signature (DeMoS) and their targeting miRNAs through Quasi-Clique detection algorithm and their application in prognosis survival study. Here we applied a cervical cancer data repository with prognosis clinical data to conduct our experiment. We first performed Empirical Bayes test using Limma method to identify dysregulated genes (or, miRNAs). MiRNA-mediated dysregulated target genes had been extracted from those dysregulated miRNAs. Thereafter, We detected dense co-expressed modules using Quasi-Clique identification technique. The average correlation coefficient was then computed for each resultant module. The module containing the highest correlation was formulated as the resultant gene signature. Next, We applied three well-known classifiers (SVM, PAM and Random Forest (RF)) using 10-fold cross-validation, and obtained AUC. Finally, we performed survival prognosis study for the resultant gene signature. Results: The resultant signature consisted of ten genes, FGF9, FGF18, PPP1R9A, ERBB4, DCDC2, TOX3, ARMC3, DNALI1, RGL3 and ENPP3. In addition, We identified a total of eight dysregulated miRNAs that targeted the aforementioned gene signature. Hsa-mir-34c was found to be strongly associated with the genes signature since its out-degree centrality score was highest. On the other hand, the p-value of the Cox regression in the prognosis study for the resultant gene signature was found to be significant (=4.2e-02). Finally, DeMoS evaluated the highest AUC values (viz., 0.95 for SVM, 0.955 for RF, 0.955 for PAM) for our resultant gene signature in compared to the other state-of-the-art techniques. Conclusions: Our framework estimated most promising gene signature that could classify multiple groups/subtypes of samples with higher AUC as well as statistically significant p-value in regression based prognosis analysis. Our method is useful to determine signature for any RNA-seq profile. Code is available at https://github.com/sahasuparna/DeMoS.

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“…Accumulating evidence has demonstrated that miRNAs regulated various carcinogenesis processes including cell maturation, cell proliferation, migration, invasion, autophagy, apoptosis, and metastasis [9]. Therefore, this suggests that miRNAs can be potential noninvasive biomarkers for cancer [8] and have a large potential to serve as promising markers in the diagnosis, prognosis, and personalized targeted therapies [9,10].…”

Section: Introductionmentioning

confidence: 99%

Hsa-mir-210 as a novel signature predicts survival in lung squamous cell carcinoma using bioinformatics analysis

Liu

Chen

et al. 2019

Preprint

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In recent years, more and more studies have shown that the expression of miRNAs is closely related to the occurrence of tumors and plays an irreplaceable role in the development and metastasis of tumors. The research was focused on lung squamous cell carcinoma. The data information is downloaded from the TCGA database and analyzed for variance, which is then verified in the GEO database. Then differential expression of miRNAs was found and survival analysis was performed, through the cut -off standard(P<0.05,|logFC|≥2), we screen the 38 up-regulated miRNAs and 14 down-regulated miRNAs from the TCGA. Finally, after the verification on the GEO database, four up-regulated miRNAs (hsa-mir-205, hsa-mir-210, hsa-mir-182, hsa-mir-224) and one downregulated miRNA (hsa-mir-451) were obtained, which provide a new direction for the diagnosis of lung squamous cell carcinoma. In the survival analysis, it was found that the expression state of hsamir-210 was significantly correlated with patient survival. The results in the univariate and multivariate Cox analysis indicated that hsa-mir-210 was an independent prognostic factor on lung squamous cell carcinoma. The functional enrichment analysis showed that hsa-mir-210 was closely related to positive and negative regulation of cell proliferation, DNA transcription, VEGF signaling pathway, MAPK signaling pathway, hif-1 signaling pathway and choline metabolic pathway. In summary, this study suggested that hsa-mir-210 could be a potential prognostic factor for lung squamous cell carcinoma. Key words：LUSC miRNA survival TCGA Author SummaryMicroRNAs are single-stranded small molecular RNA that participate in the regulation of various biological functions through indirect regulation of gene expression, and have been reported to play an important role in the occurrence, development, invasion and metastasis of tumors. In recent years, the research on miRNAs has become increasingly hot, and the role of miRNAs in tumor has been proved more and more. The subjects of this study were squamous cell carcinoma in lung cancer with relatively few studies on miRNAs. Through high-throughput data analysis, miRNAs with differential expression between lung squamous cell carcinoma tissues and normal tissues were found. These differentially expressed miRNAs provide a new direction for the early diagnosis of patients. Then, survival analysis was conducted to find the miRNAs significantly correlated with the total survival time of patients, and multi-factor analysis was conducted to exclude the influence of other clinical factors, and independent risk factors (miRNAs) affecting the survival of patients were determined, so as to provide new targets for the treatment and survival prediction of patients.

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Association of microRNA-33a Molecular Signature with Non-Small Cell Lung Cancer Diagnosis and Prognosis after Chemotherapy

Cited by 33 publications

References 40 publications

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

DeMoS: Dense Module based Gene Signature Detection through Quasi-Clique: An Application to Cervical Cancer Prognosis

Hsa-mir-210 as a novel signature predicts survival in lung squamous cell carcinoma using bioinformatics analysis

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