Identification of Differentially Expressed MiRNAs in Early-stage Cervical Cancer with Lymph Node Metastasis Across The Cancer Genome Atlas Datasets

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2018 Dec 21

PMID 30568508

Citations 8

Authors

Qian Chen

Xiaoyun Zeng

Dongping Huang

Xiaoqiang Qiu

Affiliations

Soon will be listed here.

Abstract

Background And Aim: Previous studies have suggested that lymph node metastasis (LNM) in early-stage cervical cancer (CESC) may affect the prognosis of patients and the outcomes of subsequent adjuvant therapy. However, research focused on miRNA expression in early-stage CESC patients with LNM remains limited. Therefore, it is necessary to identify prognostic miRNAs and determine their molecular mechanisms.

Methods: We evaluated the differentially expressed genes in early-stage CESC patients with LNM compared to patients without LNM and evaluated the prognostic significance of these differentially expressed genes by analyzing a public dataset from The Cancer Genome Atlas. Potential molecular mechanisms were investigated by gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses.

Results: According to the The Cancer Genome Atlas data, hsa-miR-508, hsa-miR-509-2, and hsa-miR-526b expression levels were significantly lower in early-stage CESC patients with LNM than in patients without LNM. A multivariate analysis suggested that three miRNAs were prognostic factors for CESC (<0.05). The target genes were identified to be involved in the MAPK, cAMP, PI3K/Akt, mTOR, and estrogen cancer signaling pathways. Protein-protein interaction network analysis showed that TP53, MMP1, NOTCH1, SMAD4, and NFKB1 were the most significant hub proteins.

Conclusion: Our results indicate that hsa-miR-508, hsa-miR-509-2, and hsa-miR-526b may be potential diagnostic biomarkers for early-stage CESC with LNM, and serve as prognostic predictors for patients with CESC.

Citing Articles

Value of non-coding RNAs to assess lymph node status in cervical cancer.

Dabi Y, Favier A, Razakamanantsoa L, Suisse S, Marie Y, Touboul C Front Oncol. 2023; 13:1144672.

PMID: 37234986 PMC: 10206114. DOI: 10.3389/fonc.2023.1144672.

Mesenchymal stem cell-derived exosomes as new tools for delivery of miRNAs in the treatment of cancer.

Dalmizrak A, Dalmizrak O Front Bioeng Biotechnol. 2022; 10:956563.

PMID: 36225602 PMC: 9548561. DOI: 10.3389/fbioe.2022.956563.

Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of the Rapamycin Pathway-Related Protein Expression in Lung Squamous Cell Carcinoma and Its Correlation with Lymph Node Metastasis.

Shi F, Li L J Oncol. 2022; 2022:4537256.

PMID: 36052284 PMC: 9427249. DOI: 10.1155/2022/4537256.

Metadata analysis to explore hub of the hub-genes highlighting their functions, pathways and regulators for cervical cancer diagnosis and therapies.

Reza M, Hossen M, Harun-Or-Roshid M, Siddika M, Kabir M, Haque Mollah M Discov Oncol. 2022; 13(1):79.

PMID: 35994213 PMC: 9395557. DOI: 10.1007/s12672-022-00546-6.

Bioinformatics Screening of Potential Biomarkers from mRNA Expression Profiles to Discover Drug Targets and Agents for Cervical Cancer.

Reza M, Harun-Or-Roshid M, Islam M, Hossen M, Hossain M, Feng S Int J Mol Sci. 2022; 23(7).

PMID: 35409328 PMC: 8999699. DOI: 10.3390/ijms23073968.

References

Bader G, Hogue C . An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics. 2003; 4:2. PMC: 149346. DOI: 10.1186/1471-2105-4-2. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

He L, Hannon G . MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522-31. DOI: 10.1038/nrg1379. View

Fang S, Jin X, Wang R, Li Y, Guo W, Wang N . Polymorphisms in the MMP1 and MMP3 promoter and non-small cell lung carcinoma in North China. Carcinogenesis. 2004; 26(2):481-6. DOI: 10.1093/carcin/bgh327. View

Zhang X, Hunt J, Landsittel D, Muller S, Adler-Storthz K, Ferris R . Correlation of protease-activated receptor-1 with differentiation markers in squamous cell carcinoma of the head and neck and its implication in lymph node metastasis. Clin Cancer Res. 2004; 10(24):8451-9. DOI: 10.1158/1078-0432.CCR-04-0546. View

Lewis B, Burge C, Bartel D . Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005; 120(1):15-20. DOI: 10.1016/j.cell.2004.12.035. View

Maere S, Heymans K, Kuiper M . BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 2005; 21(16):3448-9. DOI: 10.1093/bioinformatics/bti551. View

Lin S, Liu C, Yeh W, Lui M, Chang K, Chang C . Functional polymorphism in NFKB1 promoter is related to the risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers. Cancer Lett. 2006; 243(1):47-54. DOI: 10.1016/j.canlet.2005.11.019. View

Tanaka T, Watanabe T, Kazama Y, Tanaka J, Kanazawa T, Kazama S . Loss of Smad4 protein expression and 18qLOH as molecular markers indicating lymph node metastasis in colorectal cancer--a study matched for tumor depth and pathology. J Surg Oncol. 2007; 97(1):69-73. DOI: 10.1002/jso.20896. View

10.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

11.

Kamata I, Ishikawa Y, Akishima-Fukasawa Y, Ito K, Akasaka Y, Uzuki M . Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer. J Gastroenterol Hepatol. 2009; 24(9):1527-33. DOI: 10.1111/j.1440-1746.2009.05810.x. View

12.

Klug S, Ressing M, Koenig J, Abba M, Agorastos T, Brenna S . TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol. 2009; 10(8):772-84. DOI: 10.1016/S1470-2045(09)70187-1. View

13.

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

14.

Park H, Jung C, Lee S, Chae B, Lim D, Park W . Notch1 receptor as a marker of lymph node metastases in papillary thyroid cancer. Cancer Sci. 2011; 103(2):305-9. DOI: 10.1111/j.1349-7006.2011.02161.x. View

15.

Yu J, Wang Y, Dong R, Huang X, Ding S, Qiu H . Circulating microRNA-218 was reduced in cervical cancer and correlated with tumor invasion. J Cancer Res Clin Oncol. 2012; 138(4):671-4. DOI: 10.1007/s00432-012-1147-9. View

16.

Zhai Q, Zhou L, Zhao C, Wan J, Yu Z, Guo X . Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma. Biochem Biophys Res Commun. 2012; 419(4):621-6. DOI: 10.1016/j.bbrc.2012.02.060. View

17.

Tamburrino A, Molinolo A, Salerno P, Chernock R, Raffeld M, Xi L . Activation of the mTOR pathway in primary medullary thyroid carcinoma and lymph node metastases. Clin Cancer Res. 2012; 18(13):3532-40. DOI: 10.1158/1078-0432.CCR-11-2700. View

18.

Jiang H, He C, Geng S, Sheng H, Shen X, Zhang X . RhoT1 and Smad4 are correlated with lymph node metastasis and overall survival in pancreatic cancer. PLoS One. 2012; 7(7):e42234. PMC: 3409151. DOI: 10.1371/journal.pone.0042234. View

19.

Tornesello M, Buonaguro L, Buonaguro F . Mutations of the TP53 gene in adenocarcinoma and squamous cell carcinoma of the cervix: a systematic review. Gynecol Oncol. 2012; 128(3):442-8. DOI: 10.1016/j.ygyno.2012.11.017. View

20.

Zhang W, Pan Z, Yang Q, Zheng X . Tumor suppressive miR-509-5p contributes to cell migration, proliferation and antiapoptosis in renal cell carcinoma. Ir J Med Sci. 2013; 182(4):621-7. DOI: 10.1007/s11845-013-0941-y. View