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Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer.

ABSTRACT: This study aims to explore novel microRNAs in plasma for screening cancer and predicting clinical outcomes in pancreatic cancer (PCa) patients using a microRNA array-based approach.We used the Toray 3D-Gene microRNA array-based approach to compare plasma levels between PCa patients and healthy volunteers.(1) Six oncogenic microRNAs (miR-615-5p, -744, -575, -557, -675, and -550a) with high expression in plasma were selected. (2) By quantitative RT-PCR using plasma samples from 94 PCa patients and 68 healthy volunteers, a significantly higher level of plasma miR-744 in PCa patients than in healthy volunteers was validated in small-scale analysis (P=0.0038), two independent cohort analyses, and large-scale analysis (P<0.0001, AUC 0.8307). (3) miR-744 expression was significantly higher in PCa tissues (P=0.0069) and PCa cell lines (P=0.0074) than in normal tissues and fibroblasts, respectively. Preoperative plasma level of miR-744 was significantly reduced in postoperative samples (P=0.0063). (4) A high level of plasma miR-744, which was correlated with lymph node metastasis (P=0.0407) and recurrences (P=0.0376), was an independent poor prognostic factor of PCa patients after pancreatectomy (P=0.0007, HR 21.2 (3.17-436)). Furthermore, a high level of plasma miR-744 contributed to poorer progression-free survival of non-operable PCa patients who underwent gemcitabine-based chemotherapy (P=0.0533). Overexpression of miR-744 in PCa cells induced significant chemoresistance to gemcitabine in vitro.Plasma miR-744 might be useful biomarker for screening PCa, monitoring, and predicting poor prognosis and chemoresistance in PCa patients.

SUBMITTER: Miyamae M

PROVIDER: S-EPMC4815891 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other

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Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer.

Miyamae Mahito M Komatsu Shuhei S Ichikawa Daisuke D Kawaguchi Tsutomu T Hirajima Shoji S Okajima Wataru W Ohashi Takuma T Imamura Taisuke T Konishi Hirotaka H Shiozaki Atsushi A Morimura Ryo R Ikoma Hisashi H Ochiai Toshiya T Okamoto Kazuma K Taniguchi Hiroki H Otsuji Eigo E

British journal of cancer 20151027 10

<h4>Background</h4>This study aims to explore novel microRNAs in plasma for screening cancer and predicting clinical outcomes in pancreatic cancer (PCa) patients using a microRNA array-based approach.<h4>Methods</h4>We used the Toray 3D-Gene microRNA array-based approach to compare plasma levels between PCa patients and healthy volunteers.<h4>Results</h4>(1) Six oncogenic microRNAs (miR-615-5p, -744, -575, -557, -675, and -550a) with high expression in plasma were selected. (2) By quantitative R ...[more]

PMID: 26505678

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Project description:Gastric carcinoma (GC) refers to a common digestive system disease that exhibits a very high incidence. MicroRNA hsa-mir-3923 belongs to a type of miRNA, of which the function has been merely investigated in breast, pancreatic cancers and pre-neoplasic stages of gastric cancer. It has not been studied or reported in gastric carcinoma, so the relationship between gastric hsa-mir-3923 expression and the clinics feature and pathology of GC cases was examined. This study employed data mining for analyzing gastric carcinoma data in The Cancer Genome Atlas database. A Chi squared test was performed for assessing the relations of hsa-mir-3923 expression with clinics-related and pathology-regulated variables. This study conducted the assessment of the role of hsa-mir-3923 in prognostic process using Kaplan-Meier curves, Receiver operating characteristic (ROC) analysis and proportional hazards model (Cox) study. With the use of Gene Expression Omnibus, this study carried out gene set enrichment analysis (GSEA). In the meantime, the common miRNA database was compared to predict potential target genes; as revealed by co-expression analysis, a regulatory network probably existed, containing hsa-mir-3923. For the analysis of the most tightly associated cytological behavior and pathway in GC, this study adopted the databases for Annotation, Visualization and Integrated Discovery (David) and KO-Based Annotation System (KOBAS). Cytoscape, R and STRING were employed for mapping probable regulatory networks displaying relations to hsa-mir-3923. Lastly, we obtained 69 genes most tightly associated with hsa-mir-3923 and described their relationship with Circos plot. As revealed from the results, hsa-mir-3923 displayed up-regulation in gastric carcinoma, and it displayed associations with vital status, N stage and histologic grade when being expressed. The predicted results of miRNA target genes suggested that there may be a close relationship between 66 genes and hsa-mir-3923 in gastric cancer. As indicated from co-expression data, a small regulating network of 4 genes probably existed. Our results elucidated that hsa-mir-3923 high-expression reveals poor prognosis of GC patients.

Dataset Information

Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer.

Publications

Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer.

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