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Identifying cancer-related microRNAs based on subpathways.

ABSTRACT: MicroRNAs (miRNAs) are a class of small endogenous non-coding genes that play important roles in post-transcriptional regulation as well as other important biological processes. Accumulating evidence indicated that miRNAs were extensively involved in the pathology of cancer. However, determining which miRNAs are related to a specific cancer is problematic because one miRNA may target multiple genes and one gene may be targeted by multiple miRNAs. The authors proposed a new approach, named miR_SubPath, to identify cancer-associated miRNAs by three steps. The targeted genes were determined based on differentially expressed genes in significant dysfunctional subpathways. Then the candidate miRNAs were determined according to miRNA-genes associations. Finally, these candidate miRNAs were ranked based on their relations with some seed miRNAs in a functional similarity network. Results on real-world datasets showed that the proposed miR_SubPath method was more robust and could identify more cancer-related miRNAs than a prior approach, miR_Path, miR_Clust and Zhang's method.

SUBMITTER: Liu W

PROVIDER: S-EPMC8687160 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Identifying cancer-related microRNAs based on subpathways.

Liu Wenbin W Cui Zhendong Z Zan Xiangzhen X

IET systems biology 20181201 6

MicroRNAs (miRNAs) are a class of small endogenous non-coding genes that play important roles in post-transcriptional regulation as well as other important biological processes. Accumulating evidence indicated that miRNAs were extensively involved in the pathology of cancer. However, determining which miRNAs are related to a specific cancer is problematic because one miRNA may target multiple genes and one gene may be targeted by multiple miRNAs. The authors proposed a new approach, named miR_Su ...[more]

PMID: 30472691

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Project description:ImportanceAccurate clinical staging is important in rectal cancer because it determines the appropriate treatment and prognosis. Despite the use of multiple diagnostic imaging tools, it is sometimes difficult to clinically distinguish stage I tumors from stage II or III locally advanced disease. Identification of differentiating microRNAs (miRNAs) between these 2 groups may improve the clinical diagnostic power and provide insight into the biology of tumor progression.ObjectivesTo investigate differences in the expression of miRNAs in stage I vs stage II or III rectal cancers and integrate matched mRNA profiling data to identify possible functional roles of these miRNAs.Design, setting, and participantsThe primary tumor specimens from patients who were enrolled in 2 prospective clinical trials between March 24, 2004, and November 16, 2012 (American College of Surgeons Oncology Group [ACOSOG] Z6041 and Timing of Rectal Cancer Response to Chemoradiation [TIMING]) were sequenced to arrive at a set of 127 cases (41 stage I and 86 stage II or III tumors) with matched miRNA and messenger RNA (mRNA) profiling data. These findings were also evaluated in an independent cohort of 127 patient specimens (29 stage I and 98 stage II or III tumors) from The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA-READ) that also had matched miRNA and mRNA data. Data analysis was performed from September 1, 2019, to September 1, 2020.Main outcomes and measuresAlterations in miRNA expression between stage I and stage II or III tumors and their potential gene targets.ResultsA total of 254 pretreatment rectal adenocarcinoma specimens were analyzed in this study as 2 distinct cohorts: 127 samples in the ACOSOG/TIMING (stage I group: 27 [66%] male; mean [SD] age, 64.4 [10.8] years; stage II or III group: 47 [55%] male; mean [SD] age, 57.0 [11.4] years), and another 127 samples from TCGA-READ (stage I group: 17 [59%] male; mean [SD] age, 63.6 [12.0] years; stage II or III group: 48 [49%] male; mean [SD] age, 64.5 [11.4] years). A total of 19 miRNAs were overexpressed in stage II or III vs stage I tumors in both cohorts. This miRNA signature had an excellent discriminative value for distinguishing stage II or III from stage I rectal tumors (area under the curve, 0.88; 95% CI, 0.83-0.94 in ACOSOG/TIMING cohort and area under the curve, 0.84; 95% CI, 0.77-0.91 in the TCGA-READ cohort). Integrative analysis revealed 3 miRNA-mRNA pairs that exhibited significant correlations in both cohorts: miR-31-5p-SATB2, miR-143-3p-KLF5, and miR-204-5p-EZR.Conclusions and relevanceThis diagnostic study found that many of the dysregulated miRNAs in stage II or III vs stage I rectal cancers have biological implications for tumor progression. The results of this study suggest that these miRNAs could assist as diagnostic biomarkers to better identify patients with locally advanced rectal cancer.

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Identifying cancer-related microRNAs based on subpathways.

Publications

Identifying cancer-related microRNAs based on subpathways.

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