A seven-miRNA expression-based prognostic signature and its corresponding potential competing endogenous RNA network in early pancreatic cancer

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Abstract

The present study aimed to establish a microRNA (miRNA/miR) signature to predict the prognosis of patients with pancreatic cancer (PC) at the early stage and to investigate the involvement of competing endogenous RNAs (ceRNAs) in PC. Using mature miRNA expression profiles from The Cancer Genome Atlas, differentially expressed miRNAs in tissues derived from patients exhibiting early PC and tissues from healthy individuals were compared. The least absolute shrinkage and selection operator regression method was used to construct a miRNA-based signature for predicting prognosis. The miRNet tool, gene set enrichment analysis (GSEA) and the LncRNADisease database were utilized to explore the mechanistic involvement of ceRNAs. A total of seven downregulated miRNAs in PC (miR-424-5p, miR-139-5p, miR-5586-5p, miR-126-3p, miR-3613-5p, miR-454-3p and miR-1271-5p) were selected to generate a signature. Based on this seven-miRNA signature, it was possible to stratify patients with PC into low- and high-risk groups. The overall survival of the low-risk group was significantly longer than that of the high-risk group (P<0.001). The seven-miRNA signature was able to predict the 2-year-survival rate of patients with early PC with an area under the curve of 0.750. Furthermore, as opposed to routine clinicopathological features, this seven-miRNA signature was an independent prognostic factor according to multivariate Cox regression analysis. GSEA indicated that the extracellular matrix receptor interaction pathway and the transforming growth factor-β signaling pathway were enriched in the high-risk group. A ceRNA network of the seven-miR signature was constructed. In conclusion, the present study provided a seven-miRNA signature, according to which patients with early PC may be divided into high- and low-risk groups. The ceRNA network of the prognostic signature was preliminarily explored.

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Genome-wide association analysis by lasso penalized logistic regression.

Tong Wu, Yi Chen, Trevor J. Hastie … (2009)

In ordinary regression, imposition of a lasso penalty makes continuous model selection straightforward. Lasso penalized regression is particularly advantageous when the number of predictors far exceeds the number of observations. The present article evaluates the performance of lasso penalized logistic regression in case-control disease gene mapping with a large number of SNPs (single nucleotide polymorphisms) predictors. The strength of the lasso penalty can be tuned to select a predetermined number of the most relevant SNPs and other predictors. For a given value of the tuning constant, the penalized likelihood is quickly maximized by cyclic coordinate ascent. Once the most potent marginal predictors are identified, their two-way and higher order interactions can also be examined by lasso penalized logistic regression. This strategy is tested on both simulated and real data. Our findings on coeliac disease replicate the previous SNP results and shed light on possible interactions among the SNPs. The software discussed is available in Mendel 9.0 at the UCLA Human Genetics web site. Supplementary data are available at Bioinformatics online.

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Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma.

M Wagner, C Redaelli, M Lietz … (2004)

Mortality rates associated with pancreatic resection for cancer have steadily decreased with time, but improvements in long-term survival are less clear. This prospective study evaluated risk factors for survival after resection for pancreatic adenocarcinoma. Data from 366 consecutive patients recorded prospectively between November 1993 and September 2001 were analysed using univariate and multivariate models. Fifty-eight patients (15.8 per cent) underwent surgical exploration only, 97 patients (26.5 per cent) underwent palliative bypass surgery and 211 patients (57.7 per cent) resection for pancreatic adenocarcinoma. Stage I disease was present in 9.0 per cent, stage II in 18.0 per cent, stage III in 68.7 per cent and stage IV in 4.3 per cent of patients who underwent resection. Resection was curative (R0) in 75.8 per cent of patients. Procedures included pylorus-preserving Whipple resection (41.2 per cent), classical Whipple resection (37.0 per cent), left pancreatic resection (13.7 per cent) and total pancreatectomy (8.1 per cent). The in-hospital mortality and cumulative morbidity rates were 2.8 and 44.1 per cent respectively. The overall actuarial 5-year survival rate was 19.8 per cent after resection. Survival was better after curative resection (R0) (24.2 per cent) and in lymph-node negative patients (31.6 per cent). A Cox proportional hazards survival analysis indicated that curative resection was the most powerful independent predictor of long-term survival. Resection for pancreatic adenocarcinoma can be performed safely. The overall survival rate is determined by the radicality of resection. Patients deemed fit for surgery who have no radiological signs of distant metastasis should undergo surgical exploration. Resection should follow if there is a reasonable likelihood that an R0 resection can be obtained. Copyright 2004 British Journal of Surgery Society Ltd.

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miRNA sponges: soaking up miRNAs for regulation of gene expression.

Rasmus O Bak, Jacob Giehm Mikkelsen (2016)

MicroRNAs (miRNAs) are small regulatory RNAs that act in an entangled web of interactions with target mRNAs to shape the cellular protein landscape by post-transcriptional control of mRNA decay and translation. miRNAs are themselves subject to numerous regulatory mechanisms that adjust their prevalence and activity. Emerging evidence suggests that miRNAs are themselves targeted by regulatory RNA species, and the identification of several classes of noncoding RNA molecules carrying miRNA binding sites has added a new intricate dimension to miRNA regulation. Such miRNA 'sponges' bind miRNAs and competitively sequester them from their natural targets. Endogenous miRNA sponges, also termed competing endogenous RNAs (ceRNAs), act to buffer the activity of miRNAs on physiologically relevant targets. This class of sponges includes endogenously transcribed pseudogenes, long noncoding RNAs, and recently discovered circular RNAs and may act in large complex networks in conjunction with miRNAs to regulate the output of protein. With the growing demand of regulating miRNA activity for experimental purposes and potential future clinical use, naturally occurring miRNA sponges are providing inspiration for engineering of gene vector-encoded sponges as potent inhibitors of miRNA activity. Combined with potent and versatile vector technologies, expression of custom-designed sponges provides new means of managing miRNAs and soaking up miRNAs for therapeutic regulation of gene expression. © 2013 John Wiley & Sons, Ltd.

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Author and article information

Journal

Journal ID (nlm-ta): Exp Ther Med

Journal ID (iso-abbrev): Exp Ther Med

Journal ID (publisher-id): ETM

Title: Experimental and Therapeutic Medicine

Publisher: D.A. Spandidos

ISSN (Print): 1792-0981

ISSN (Electronic): 1792-1015

Publication date (Print): September 2019

Publication date (Electronic): 03 July 2019

Publication date PMC-release: 03 July 2019

Volume: 18

Issue: 3

Pages: 1601-1608

Affiliations

[1 ]Department of Medical Oncology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, P.R. China

[2 ]Department of Medical Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China

[3 ]Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, Guangxi 530029, P.R. China

[4 ]Department of Surgery 1, Minzu Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530001, P.R. China

Author notes

Correspondence to: Dr Liusheng He, Department of Surgery 1, Minzu Hospital of Guangxi Zhuang Autonomous Region, 232 Mingxiu Road, Nanning, Guangxi 530001, P.R. China, E-mail: liusheng_he@ 123456126.com

Dr Yufeng Lv, Department of Medical Oncology, Affiliated Langdong Hospital of Guangxi Medical University, 60 Xiangbin Road, Nanning, Guangxi 530029, P.R. China, E-mail: tougaozhuanyong_lv@ 123456126.com

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Publisher ID: ETM-0-0-7728

DOI: 10.3892/etm.2019.7728

PMC ID: 6676175

PubMed ID: 31410115

SO-VID: 968885c3-2e66-4399-b4c1-735c0203763c

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

A seven-miRNA expression-based prognostic signature and its corresponding potential competing endogenous RNA network in early pancreatic cancer

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RNA drug delivery

Most cited references 23

Genome-wide association analysis by lasso penalized logistic regression.

Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma.

miRNA sponges: soaking up miRNAs for regulation of gene expression.

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