Meng Wen-Jian, Yang Lie, Ma Qin, Zhang Hong, Adell Gunnar, Arbman Gunnar, Wang Zi-Qiang, Li Yuan, Zhou Zong-Guang, Sun Xiao-Feng
From the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China (W-JM, LY, QM, Z-QW, Z-GZ); School of Medicine, Örebro University, Örebro (HZ); Department of Oncology, County Council of Östergötland, Linköping (GA); Department of Surgery, Vrinnevi Hospital, University of Linköping, Norrköping, Sweden (GA); Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China (YL, Z-GZ, X-FS); and Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden (X-FS).
Medicine (Baltimore). 2015 Aug;94(32):e1297. doi: 10.1097/MD.0000000000001297.
The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P = 0.012), coexistence of adenoma (P = 0.012), microsatellite instability (P = 0.024), and less glucose transporter 1 (P = 0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.
异常微小RNA（miRNA，miR）的表达是结直肠癌（CRC）的一个普遍特征。同步性结直肠癌的病理特征和临床行为已得到全面描述；然而，同步性结直肠癌中miRNA和小核仁RNA（snoRNA）的表达谱尚未阐明。在本研究中，通过微阵列评估了5例同步性结直肠癌及其配对的正常结直肠组织中miRNA和snoRNA的表达谱。对从miRNA-mRNA相互作用预测的假定靶标进行了功能和通路分析。此外，在一项回顾性队列研究中，我们分析了22例同步性结直肠癌患者和579例孤立性结直肠癌患者的临床病理和分子特征。我们发现同步性结直肠癌中miRNA存在整体失调，包括致癌性miR-17-92簇和抑癌性miR-143-145簇，以及snoRNA。差异性miRNA而非snoRNA表达足以将同步性癌与正常黏膜区分开来。对假定靶标的功能分析表明，miRNA簇可能调节参与同步性结直肠癌发病机制的致癌途径的多个效应器。同步性和孤立性结直肠癌正常黏膜的比较表明，同步性结直肠癌在致癌过程中与孤立性结直肠癌存在不同的遗传背景。与孤立性癌患者相比，同步性病例表现出多个结肠外癌症（P = 0.012）、腺瘤共存（P = 0.012）、微卫星不稳定性（P = 0.024）以及葡萄糖转运蛋白1较少（P = 0.037）。异常的miRNA表达谱可能潜在地用作同步性结直肠癌的诊断工具。我们的发现代表了同步性结直肠癌首个全面的miRNA和snoRNA表达特征，表明miRNA和snoRNA可能是同步性结直肠癌的治疗靶点。
