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:BackgroundPleural effusion (PE) caused by lung cancer is prevalent, and it is difficult to differentiate it from PE caused by tuberculosis. Exosome-based liquid biopsy offers a non-invasive technique to diagnose benign and malignant PE. Exosomal miRNAs are potential diagnostic markers and play an essential role in signal transduction and biological processes in tumor development. We hypothesized that exosomal miRNA expression profiles in PE would contribute to identifying its diagnostic markers and elucidating the molecular basis of PE formation in lung cancer.MethodsThe exosomes from PE caused by lung adenocarcinoma (LUAD) and pulmonary tuberculosis were isolated and verified by transmission electron microscopy. The exosomal miRNA profiles were identified using deep sequencing and validated with quantitative real-time PCR (qRT-PCR). We performed bioinformatic analysis for differentially expressed miRNAs to explore how exosomal miRNAs regulate pleural effusion.ResultsWe identified 99 upregulated and 91 downregulated miRNAs in malignant pleural effusion (MPE) compared to tuberculous pleural effusion (TPE). Seven differentially expressed miRNAs (DEmiRNAs) were validated by qRT-PCR, out of which 5 (71.4%) were confirmed through sequencing. Gene Ontology (GO) analysis revealed that most exosomal miRNAs target genes were involved in regulating cellular processes and nitrogen compound metabolism. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the exosomal miRNAs target genes were mainly involved in Fc gamma R-mediated phagocytosis, Rap1 signaling pathway, and breast cancer. The hub genes, including ITGAM, FOXO1, MAPK14, YWHAB, GRIN1, and PRF1, were screened through plug-in cytoHubba. The PFR1 was identified as a critical gene in MPE formation using single-cell sequencing analysis. Additionally, we hypothesized that tumor cells affected natural killer cells and promoted the generation of PE in LUAD via the exosomal hsa-miR-3120-5p-PRF1 axis.ConclusionsWe identified exosomal miRNA profiles in LUAD-MPE and TPE, which may help in the differential diagnosis of MPE and TPE. Bioinformatic analysis revealed that these miRNAs might affect PE generation through tumor immune response in LUAD. Our results provided a new theoretical basis for understanding the function of exosomal miRNAs in LUAD-MPE.

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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