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Screening candidate microRNA-mRNA regulatory pairs for predicting the response to chemoradiotherapy in rectal cancer by a bioinformatics approach.

ABSTRACT: Extensive efforts have been undertaken in search of biomarkers for predicting the chemoradiotherapy response in rectal cancer. However, most attention on treatment efficiency prediction in carcinoma is addicted to single or limited molecules. Network biomarkers are considered to outperform single molecules in predictive power. In this study, candidate microRNAs (miRNAs) were identified from the PubMed citations and miRNA expression profiles. Targets of miRNAs were obtained from four experimentally confirmed interactions and three computationally predicted databases. Functional enrichment analysis of all the targets revealed their associations with chemoradiotherapy response, indicating they could be promising biomarkers. Two lists of key target mRNAs of the candidate miRNAs were retrieved from protein-protein interaction (PPI) network and mRNA expression profiles, respectively. Pathway analysis and literature validation revealed that the mRNA lists were highly related to the ionizing radiation. The above miRNAs along with the key miRNA targets provide potential miRNA-mRNA regulatory pairs as network biomarkers in which all the network components may be used for predicting the chemoradiotherapy response. These results demonstrated that the network biomarkers could provide a useful model for predicting the chemoradiotherapy response and help in further understanding the molecular basis of response differences, which should be prioritized for further study.

SUBMITTER: Peng Q

PROVIDER: S-EPMC5595906 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Screening candidate microRNA-mRNA regulatory pairs for predicting the response to chemoradiotherapy in rectal cancer by a bioinformatics approach.

Peng Qiliang Q Zhu Junjia J Shen Peipei P Yao Wenyan W Lei Yu Y Zou Li L Xu Yingying Y Shen Yuntian Y Zhu Yaqun Y

Scientific reports 20170912 1

Extensive efforts have been undertaken in search of biomarkers for predicting the chemoradiotherapy response in rectal cancer. However, most attention on treatment efficiency prediction in carcinoma is addicted to single or limited molecules. Network biomarkers are considered to outperform single molecules in predictive power. In this study, candidate microRNAs (miRNAs) were identified from the PubMed citations and miRNA expression profiles. Targets of miRNAs were obtained from four experimental ...[more]

PMID: 28900297

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Project description:The incorporation of chemoradiation prior to resection of the tumour has revolutionized the management of locally advanced rectal cancer. However, a large proportion of these patients are resistant to preoperative treatment schedule. We recently reported that c-Myc gene expression correlates negatively with this resistance in patients with rectal cancer. In this study, we carried out integrated analysis of miRNA and mRNA expression profiling in 45 pre-treatment rectal tumour. Further, expression of miRNAs and c-Myc, and their relationship with clinicopathological factors and patient survival was analysed. As a result, we found that 12 miRNAs were differentially expressed between responder and non-responder rectal cancer patients. Functional classification revealed an association between differentially expressed miRNAs and c-Myc. Subsequent quantitative real-time PCR results showed that both, miRNA-148 and miRNA-375 levels were significantly lower in responder compared to non-responder patients. Notably, the higher level of miRNA-375 was significantly negatively correlated with c-Myc. These results suggest that miRNA-375 and its targeted c-Myc play an important role as predictive biomarker of response to neoadjuvant treatment in patients with locally advanced rectal cancer, but still not suitable for prognosis. Pre-treatment biopsies of 22 patients with LARC were prospectively collected and freshly frozen according to an institutional board-approved protocol. Tumour response was assessed in surgical specimens by pathological examination based on the semi-quantitative tumour regression grading (TRG) system described by Mandard in 1994[36]: TRG1 and TRG2 scores were considered responders, whereas TRG3, TRG4, and TRG5 were classified as non-responders. The inclusion criteria were: histologically proven rectal tumour at a clinical stage UICC II-III (cT3-4/and or N positive), following endorectal ultrasound and/or MRI scan. Patients were excluded if they had the tumour located above 13 cm from the anal verge by rigid rectoscopy, synchronic colonic cancer assessed by colonoscopy, distant metastases by 18FDG PET-CT scan, and suspicion of hereditary colorectal cancer. All patients subsequently received a total dose of 50.4Gy of radiation (28 fractions of 1.8Gy) associated with capecitabine (oral form of 5-FU) with or without oxaliplatine, according to our Hospital Clinical Practice Guidelines. Standardized Surgery was performed, including total mesorectal excision, following an interval of 8-10 weeks after completion of CT/RT.

Dataset Information

Screening candidate microRNA-mRNA regulatory pairs for predicting the response to chemoradiotherapy in rectal cancer by a bioinformatics approach.

Publications

Screening candidate microRNA-mRNA regulatory pairs for predicting the response to chemoradiotherapy in rectal cancer by a bioinformatics approach.

Similar Datasets

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