Three-microRNA Signature Identified by Bioinformatics Analysis Predicts Prognosis of Gastric Cancer Patients

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2018 Mar 24

PMID 29568201

Citations 27

Authors

Cheng Zhang

Chun-Dong Zhang

Ming-Hui Ma

Dong-Qiu Dai

Affiliations

Soon will be listed here.

Abstract

Aim: To identify multiple microRNAs (miRNAs) for predicting the prognosis of gastric cancer (GC) patients by bioinformatics analysis.

Methods: The original microarray dataset GSE93415, which included 20 GC and 20 tumor adjacent normal gastric mucosal tissues, was downloaded from the Gene Expression Omnibus database and used for screening differentially expressed miRNAs (DEMs). The cut-off criteria were < 0.05 and fold change > 2.0. In addition, we acquired the miRNA expression profiles and clinical information of 361 GC patients from The Cancer Genome Atlas database to assess the prognostic role of the DEMs. The target genes of miRNAs were predicted using TargetScan, miRDB, miRWalk, and DIANA, and then the common target genes were selected for functional enrichment analysis.

Results: A total of 110 DEMs including 19 up-regulated and 91 down-regulated miRNAs were identified between 20 pairs of GC and tumor adjacent normal tissues, and the Kaplan-Meier survival analysis found that a three-miRNA signature (miR-145-3p, miR-125b-5p, and miR-99a-5p) had an obvious correlation with the survival of GC patients. Furthermore, univariate and multivariate Cox regression analyses indicated that the three-miRNA signature could be a significant prognostic marker in GC patients. The common target genes of the three miRNAs are added up to 108 and used for Gene Functional Enrichment analysis. Biological Process and Molecular Function analyses showed that the target genes are involved in cell recognition, gene silencing and nucleic acid binding, transcription factor activity, and transmembrane receptor activity. Cellular Component analysis revealed that the genes are portion of nucleus, chromatin silencing complex, and TORC1/2 complex. Biological Pathway analysis indicated that the genes participate in several cancer-related pathways, such as the focal adhesion, PI3K, and mTOR signaling pathways.

Conclusion: This study justified that a three-miRNA signature could play a role in predicting the survival of GC patients.

Citing Articles

Shared and specific competing endogenous RNAs network mining in four digestive system tumors.

Tang Y, Fahira A, Lin S, Shao Y, Huang Z Comput Struct Biotechnol J. 2024; 23:4271-4287.

PMID: 39669749 PMC: 11635987. DOI: 10.1016/j.csbj.2024.11.005.

Bioinformatics Analysis and Validation of Potential Markers Associated with Prediction and Prognosis of Gastric Cancer.

Matsuoka T, Yashiro M Int J Mol Sci. 2024; 25(11).

PMID: 38892067 PMC: 11172243. DOI: 10.3390/ijms25115880.

MicroRNA biomarkers and their use in evaluating the prognosis of lung cancer.

Wu R, Zhang B, He M, Kang Y, Zhang G J Cancer Res Clin Oncol. 2023; 149(18):16753-16761.

PMID: 37728700 DOI: 10.1007/s00432-023-05404-8.

Two-in-One Nanoparticle Formulation to Deliver a Tyrosine Kinase Inhibitor and microRNA for Targeting Metabolic Reprogramming and Mitochondrial Dysfunction in Gastric Cancer.

Lo Y, Wang T, Chen C, Chang Y, Lin A Pharmaceutics. 2022; 14(9).

PMID: 36145507 PMC: 9504622. DOI: 10.3390/pharmaceutics14091759.

MiR-942-3p as a Potential Prognostic Marker of Gastric Cancer Associated with AR and MAPK/ERK Signaling Pathway.

Liu W, Ying N, Rao X, Chen X Curr Issues Mol Biol. 2022; 44(9):3835-3848.

PMID: 36135175 PMC: 9498168. DOI: 10.3390/cimb44090263.

References

Zhang L, Huang Z, Zhang H, Zhu M, Zhu W, Zhou X . Prognostic value of candidate microRNAs in gastric cancer: A validation study. Cancer Biomark. 2016; 18(3):221-230. DOI: 10.3233/CBM-160091. View

Yang J, Zhang H, Qin C . MicroRNA-217 functions as a prognosis predictor and inhibits pancreatic cancer cell proliferation and invasion via targeting E2F3. Eur Rev Med Pharmacol Sci. 2017; 21(18):4050-4057. View

Zeng Z, Wang J, Zhao L, Hu P, Zhang H, Tang X . Potential role of microRNA-21 in the diagnosis of gastric cancer: a meta-analysis. PLoS One. 2013; 8(9):e73278. PMC: 3762732. DOI: 10.1371/journal.pone.0073278. View

Fang Z, Tang J, Bai Y, Lin H, You H, Jin H . Plasma levels of microRNA-24, microRNA-320a, and microRNA-423-5p are potential biomarkers for colorectal carcinoma. J Exp Clin Cancer Res. 2015; 34:86. PMC: 4546358. DOI: 10.1186/s13046-015-0198-6. View

Parkin D . The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006; 118(12):3030-44. DOI: 10.1002/ijc.21731. View

Teng C, Zheng H . Low expression of microRNA-1908 predicts a poor prognosis for patients with ovarian cancer. Oncol Lett. 2017; 14(4):4277-4281. PMC: 5604148. DOI: 10.3892/ol.2017.6714. View

Chen W, Zheng R, Zhang S, Zhao P, Li G, Wu L . Report of incidence and mortality in China cancer registries, 2009. Chin J Cancer Res. 2013; 25(1):10-21. PMC: 3555299. DOI: 10.3978/j.issn.1000-9604.2012.12.04. View

Wang P, Yang D, Zhang H, Wei X, Ma T, Cheng Z . Early Detection of Lung Cancer in Serum by a Panel of MicroRNA Biomarkers. Clin Lung Cancer. 2015; 16(4):313-9.e1. DOI: 10.1016/j.cllc.2014.12.006. View

Chen Y, Fu L, Wen X, Liu B, Huang J, Wang J . Oncogenic and tumor suppressive roles of microRNAs in apoptosis and autophagy. Apoptosis. 2014; 19(8):1177-89. DOI: 10.1007/s10495-014-0999-7. View

10.

Wu J, Wang J, Jiang X, Lan J, He X, Wang H . MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis. Gastric Cancer. 2014; 18(4):729-39. DOI: 10.1007/s10120-014-0421-8. View

11.

Liu M, Li C, Chen Z, Ji R, Guo Q, Li Q . Celecoxib regulates apoptosis and autophagy via the PI3K/Akt signaling pathway in SGC-7901 gastric cancer cells. Int J Mol Med. 2014; 33(6):1451-8. PMC: 4055439. DOI: 10.3892/ijmm.2014.1713. View

12.

Nohata N, Hanazawa T, Kinoshita T, Okamoto Y, Seki N . MicroRNAs function as tumor suppressors or oncogenes: aberrant expression of microRNAs in head and neck squamous cell carcinoma. Auris Nasus Larynx. 2012; 40(2):143-9. DOI: 10.1016/j.anl.2012.07.001. View

13.

Li W, Wang Y, Zhang Q, Tang L, Liu X, Dai Y . MicroRNA-486 as a Biomarker for Early Diagnosis and Recurrence of Non-Small Cell Lung Cancer. PLoS One. 2015; 10(8):e0134220. PMC: 4523212. DOI: 10.1371/journal.pone.0134220. View

14.

Filipowicz W, Bhattacharyya S, Sonenberg N . Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat Rev Genet. 2008; 9(2):102-14. DOI: 10.1038/nrg2290. View

15.

Zhang Y, Xu W, Ni P, Li A, Zhou J, Xu S . MiR-99a and MiR-491 Regulate Cisplatin Resistance in Human Gastric Cancer Cells by Targeting CAPNS1. Int J Biol Sci. 2016; 12(12):1437-1447. PMC: 5166486. DOI: 10.7150/ijbs.16529. View

16.

Liu X, Kwong A, Sihoe A, Chu K . Plasma miR-940 may serve as a novel biomarker for gastric cancer. Tumour Biol. 2015; 37(3):3589-97. DOI: 10.1007/s13277-015-4019-5. View

17.

Goto Y, Kurozumi A, Arai T, Nohata N, Kojima S, Okato A . Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer. Br J Cancer. 2017; 117(3):409-420. PMC: 5537499. DOI: 10.1038/bjc.2017.191. View

18.

Pathan M, Keerthikumar S, Ang C, Gangoda L, Quek C, Williamson N . FunRich: An open access standalone functional enrichment and interaction network analysis tool. Proteomics. 2015; 15(15):2597-601. DOI: 10.1002/pmic.201400515. View

19.

Lin H, Yang M, Wu C, Chen P, Yang Y, Chu Y . 2-Methoxyestradiol attenuates phosphatidylinositol 3-kinase/Akt pathway-mediated metastasis of gastric cancer. Int J Cancer. 2007; 121(11):2547-55. DOI: 10.1002/ijc.22963. View

20.

Merhautova J, Demlova R, Slaby O . MicroRNA-Based Therapy in Animal Models of Selected Gastrointestinal Cancers. Front Pharmacol. 2016; 7:329. PMC: 5037200. DOI: 10.3389/fphar.2016.00329. View