Dataset Information

Plasma and Tissue Specific miRNA Expression Pattern and Functional Analysis Associated to Colorectal Cancer Patients.

ABSTRACT: An increasing number of studies suggest the implication of microRNAs (miRNAs) in colorectal (CRC) carcinogenesis and disease progression. Nevertheless, the basic mechanism is not yet clear. We determined plasma miRNA expression levels using Agilent microarray technology followed by overlapping with The Cancer Genome Atlas (TCGA) tissue data and a qRT-PCR validation step and analysis of the altered miRNA signatures to emphasize new mechanistic insights. For TGCA dataset, we identified 156 altered miRNAs (79 downregulated and 77 upregulated) in colorectal tissue samples versus normal tissue. The microarray experiment is based on 16 control samples, 38 CRC plasma samples from colorectal cancer patients who have not undergone chemotherapy, and 17 chemo-treated samples. In the case of the analysis of CRC cancer versus healthy control we identified 359 altered miRNAs (214 downregulated and 60 upregulated), considering as the cutoff value a fold-change of ±1.5 and p < 0.01. An additional microarray analysis was performed on plasma from untreated colorectal cancer (n = 38) and chemotherapy-treated colorectal cancer patients (n = 17), which revealed 15 downregulated miRNAs and 53 upregulated miRNAs, demonstrating that the plasma miRNA pattern is affected by chemotherapy and emphasizing important regulators of drug resistance mechanisms. For the validation of the microarray data, we selected a panel of 4 miRNAs from the common miRNA signatures for colon and rectal cancer (miR-642b-3p, miR-195-5p and miR-4741). At the tissue level, the expression levels were in agreement with those observed in colorectal plasma. miR-1228-3p, the top upregulated miRNA in CRC, was chosen to be validated on tissue and plasma samples, as it was demonstrated to be downregulated at tissue level in our patient cohort. This was confirmed by TCGA data and was one example of ta ranscript that has a different expression level between tumor tissue and plasma. Developing more efficient investigation methods will help explain the mechanisms responsible for miRNAs released in biofluids, which is the most upregulated transcript in colorectal plasma samples and which can function as a prediction tool within the oncological field.

SUBMITTER: Cojocneanu R

PROVIDER: S-EPMC7226631 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Plasma and Tissue Specific miRNA Expression Pattern and Functional Analysis Associated to Colorectal Cancer Patients.

Cojocneanu Roxana R Braicu Cornelia C Raduly Lajos L Jurj Ancuta A Zanoaga Oana O Magdo Lorand L Irimie Alexandru A Muresan Mihai-Stefan MS Ionescu Calin C Grigorescu Mircea M Berindan-Neagoe Ioana I

Cancers 20200331 4

An increasing number of studies suggest the implication of microRNAs (miRNAs) in colorectal (CRC) carcinogenesis and disease progression. Nevertheless, the basic mechanism is not yet clear. We determined plasma miRNA expression levels using Agilent microarray technology followed by overlapping with The Cancer Genome Atlas (TCGA) tissue data and a qRT-PCR validation step and analysis of the altered miRNA signatures to emphasize new mechanistic insights. For TGCA dataset, we identified 156 altered ...[more]

PMID: 32244548

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Project description:Background: Chemotherapy is one of the most common therapies used in the treatment of colorectal cancer (CRC), but chemoresistance inevitably occurs. It is challenging to obtain an immediate and accurate diagnosis of chemoresistance. The potential of circulating exosomal miRNAs as oxaliplatin-based chemoresistant biomarkers in CRC patients was investigated in this study. Methods: Plasma exosomal miRNAs in sensitive and resistant patients were analyzed by miRNA microarray analysis, followed by verification with a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay in two independent cohorts. The diagnostic accuracy was determined by ROC curve analysis. Logistic regression analysis and Spearman's rank correlation test were also performed. Finally, bioinformatics was used to preliminarily explore the potential molecular mechanism of the selected miRNAs in chemoresistance. Results: miRNA microarray analysis identified four upregulated miRNAs and 20 downregulated miRNAs in chemoresistant patients compared to chemosensitive patients. Twelve markedly dysregulated miRNAs were selected for further investigation, of which six (miR-100, miR-92a, miR-16, miR-30e, miR-144-5p, and let-7i) were verified to be significantly and consistently dysregulated (>1.5-fold, P < 0.05). The combination of the six miRNAs had the highest AUC (0.825, 95% CI, 0.753-0.897). The expression level of these 6 miRNAs was not correlated with tumor location, stage, or chemotherapy program. Only miR-100 was significantly upregulated in low histological grade. GO analysis and KEGG pathway analysis showed that miRNAs were related to RNA polymerase II transcription and enriched in the PI3K-AKT signaling pathway, AMPK signaling pathway, and FoxO signaling pathway. Conclusions: We identified a panel of plasma exosomal miRNAs, containing miR-100, miR-92a, miR-16, miR-30e, miR-144-5p, and let-7i, that could significantly distinguish chemoresistant patients from chemosensitive patients. The detection of circulating exosomal miRNAs may serve as an effective way to monitor CRC patient responses to chemotherapy. Targeting these miRNAs may also be a promising strategy for CRC treatment.

Dataset Information

Plasma and Tissue Specific miRNA Expression Pattern and Functional Analysis Associated to Colorectal Cancer Patients.

Publications

Plasma and Tissue Specific miRNA Expression Pattern and Functional Analysis Associated to Colorectal Cancer Patients.

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