Dataset Information

Bioinformatic Interrogation of 5p-arm and 3p-arm Specific miRNA Expression Using TCGA Datasets.

ABSTRACT: MicroRNAs (miRNAs) play important roles in cellular functions and developmental processes. They are also implicated in oncogenesis mechanisms and could serve as potential cancer biomarkers. Using high-throughput miRNA sequencing information, expression of both the 5p-arm and 3p-arm mature miRNAs were demonstrated and generated from the single miRNA hairpin precursor. However, current miRNA annotations lack comprehensive 5p-arm/3p-arm feature annotations. Among known human mature miRNAs, only half of them are annotated with arm features. This generated ambiguous results in many miRNA-Sequencing (miRNA-Seq) studies. In this report, we have interrogated the TCGA (the Cancer Genome Atlas) miRNA expression datasets with an improved, fully annotated human 5p-arm and 3p-arm miRNA reference list. By utilizing this comprehensive miRNA arm-feature annotations, enhanced determinations and clear annotations were achieved for the miRNA isoforms (isomiRs) recognized from the sequencing reads. In the gastric cancer (STAD) dataset, as an example, 32 5p-arm/3p-arm OPEN ACCESS J. Clin. Med. 2015, 4 1799 specific miRNAs were found to be down-regulated and 24 5p-arm/3p-arm specific miRNAs were found to be up-regulated. We have further extended miRNA biomarker discoveries to additional TCGA miRNA-Seq datasets and provided extensive expression information on 5p-arm/3p-arm miRNAs across multiple cancer types. Our results identified several miRNAs that could be potential common biomarkers for human cancers.

SUBMITTER: Kuo WT

PROVIDER: S-EPMC4600160 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Bioinformatic Interrogation of 5p-arm and 3p-arm Specific miRNA Expression Using TCGA Datasets.

Kuo Wei-Ting WT Su Ming-Wei MW Lee Yungling Leo YL Chen Chien-Hsiun CH Wu Chew-Wun CW Fang Wen-Liang WL Huang Kuo-Hung KH Lin Wen-Chang WC

Journal of clinical medicine 20150915 9

MicroRNAs (miRNAs) play important roles in cellular functions and developmental processes. They are also implicated in oncogenesis mechanisms and could serve as potential cancer biomarkers. Using high-throughput miRNA sequencing information, expression of both the 5p-arm and 3p-arm mature miRNAs were demonstrated and generated from the single miRNA hairpin precursor. However, current miRNA annotations lack comprehensive 5p-arm/3p-arm feature annotations. Among known human mature miRNAs, only hal ...[more]

PMID: 26389959

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Project description:Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had <1% or >97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival (p > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (p < 0.05). They were enriched for SNVs in TP53, and depleted for point mutations in CASP8, HRAS, HLA-A, HUWE1, HLA-B, and COL22A1 (false discovery rate, FDR < 0.05). 3p arm loss was associated with CNAs across the whole genome (FDR < 0.1), and pathway analysis revealed low lymphoid-non-lymphoid cell interactions and cytokine signaling (FDR < 0.1). In the tumor microenvironment, 3p arm lost tumors had low immune cell infiltration (FDR < 0.1) and elevated hypoxia (FDR < 0.1). 3p arm lost tumors had lower abundance of proteins phospho-HER3 and ANXA1, and higher abundance of miRNAs hsa-miR-548k and hsa-miR-421, which were all associated with survival. There were no molecular differences by 3p arm status in HPV-positive patients, at least at our statistical power level. 3p arm loss is largely an all or none phenomenon in HPV-negative disease and does not predict poorer survival from the time of diagnosis in TCGA cohort. However, it produces tumors with distinct molecular characteristics and may represent a clinically useful biomarker to guide treatment decisions for HPV-negative patients.

Dataset Information

Bioinformatic Interrogation of 5p-arm and 3p-arm Specific miRNA Expression Using TCGA Datasets.

Publications

Bioinformatic Interrogation of 5p-arm and 3p-arm Specific miRNA Expression Using TCGA Datasets.

Similar Datasets

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