Dataset Information

Plasma Exosomal miRNA Expression Profile as Oxaliplatin-Based Chemoresistant Biomarkers in Colorectal Adenocarcinoma.

ABSTRACT: 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.

SUBMITTER: Han J

PROVIDER: S-EPMC7531016 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Plasma Exosomal miRNA Expression Profile as Oxaliplatin-Based Chemoresistant Biomarkers in Colorectal Adenocarcinoma.

Han Jiayi J Sun Wu W Liu Rui R Zhou Zhen Z Zhang Haiyang H Chen Xi X Ba Yi Y

Frontiers in oncology 20200918

<b>Background:</b> 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. <b>Methods:</b> Plasma exosomal miRNAs in sensitive and resistant patients were analyzed by miRNA microarray analysis, ...[more]

PMID: 33072545

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Project description:Background:Exosomes are extracellular vesicles secreted by a variety of cells and are widely distributed in human body fluids. Exosomal long non-coding RNA (lncRNA) is a by-product of gene transcription and is involved in the regulation of cancer cell growth and migration. Numerous studies have identified aberrant lncRNA levels in pancreatic cancer (PC), but studies on exosomal lncRNA expression in pancreatic ductal adenocarcinoma (PDAC) plasma are relatively few and remain largely unknown. Methods:We studied the expression of exosomal lncRNAs and mRNAs in the plasma of 5 PDAC patients and 5 healthy human subjects using high-throughput sequencing. Results:A total of 43715 exosomal lncRNAs were found to be expressed in PDAC and healthy human plasma, of which 5851 were up-regulated, and 1055 were down-regulated in all 5 PDAC plasma (≥2.0-fold change, P<0.05). The expression of eight significantly expressed genes (ABCD4, RP11-77P6.2, FLVCR1-AS1, HMBOX1, TUBA1C, RP11-115C21.2, PRKG1-AS1, and MTATP6P1) were selected to be measured in 5 patients using database and real-time quantitative reverse transcription PCR (qRT-PCR), and the data were consistent with those obtained from high-throughput sequencing. Analysis of their nearby coding genes (mRNAs) showed that the principal functions of most genes were to regulate cell metabolism process, apoptosis, protein binding and receptor binding. The main regulatory pathways included the ErbB signaling pathway, which regulates cell proliferation and differentiation, and the tumour pathway. Analysis of the co-expressed gene regulatory network identified key lncRNA-mRNA pairs that may play an important role in the pathogenesis of PDAC. Conclusions: Expression differences in exosomal lncRNAs exist between PDAC and healthy human plasma, so the expression profile of exosomal lncRNAs could explain the onset and development of PDAC and could also serve as a candidate biomarker for the diagnosis of PDAC and a potential therapeutic target.

Project description:Background: Colorectal cancer (CRC) is currently the fourth most common cancer worldwide. The roles of exosomal competing endogenous RNAs (ceRNAs) in CRC remain unclear. In this study, we constructed an exosomal ceRNA network to identify the core ceRNAs and investigate the diagnostic biomarkers in CRC. Methods and Patients: Serum exosomes were isolated from four CRC patients and two healthy donors by ultracentrifugation, and then subjected to RNA isolation, sequencing and microarray. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were performed to identify functional enrichment implications of differentially expressed exosomal mRNAs. TargetScan and miRanda were used for identifying the miRNA-mRNA and miRNA-LncRNA interactions. The predicted lncRNAs and mRNAs were intersected with the differentially expressed genes, for which the screening criterion was fold change >1.5 in the microarray. Differentially expressed exosomal miRNAs were identified in the GSE71008 dataset, and differentially expressed mRNAs (DEmRNAs) were further summarized from The Cancer Genome Atlas (TCGA) database. Results: A total of 1186 exosomal DEmRNAs, 2088 exosomal DElncRNAs and 29 exosomal miRNAs were detected in CRC patients compared to the healthy donors. Functional enrichment analysis suggested that exosomal DEmRNAs might participate in pathways related to carcinogenesis and development of cancer. An exosomal ceRNA regulatory network of CRC was constructed based on 40 lncRNAs, two miRNAs, and five mRNAs. Exosomal miR-150-5p and miR-10b-5p expression levels were increased in healthy donors compared with CRC patients in the GSE71008 dataset, and five DEmRNAs (TOMM70A, RBM48, BEND3, RHOBTB1, and ADAMTS2) were significantly upregulated in TCGA database. Two potential exosomal regulatory axes of lncRNA G016261-miR-150-5p-RBM48 and lncRNA XLOC_011677-miR-10b-5p-BEND3 were identified from the network. Conclusion: The current study revealed potential molecular biological regulation pathways and diagnostic biomarkers through the exosomal ceRNA regulatory network.

Dataset Information

Plasma Exosomal miRNA Expression Profile as Oxaliplatin-Based Chemoresistant Biomarkers in Colorectal Adenocarcinoma.

Publications

Plasma Exosomal miRNA Expression Profile as Oxaliplatin-Based Chemoresistant Biomarkers in Colorectal Adenocarcinoma.

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