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与T1期结直肠癌淋巴结转移相关的微小RNA特征

A MicroRNA Signature Associated With Metastasis of T1 Colorectal Cancers to Lymph Nodes.

作者信息

Ozawa Tsuyoshi, Kandimalla Raju, Gao Feng, Nozawa Hiroaki, Hata Keisuke, Nagata Hiroshi, Okada Satoshi, Izumi Daisuke, Baba Hideo, Fleshman James, Wang Xin, Watanabe Toshiaki, Goel Ajay

机构信息

Center for Gastrointestinal Research and Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.

Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.

出版信息

Gastroenterology. 2018 Mar;154(4):844-848.e7. doi: 10.1053/j.gastro.2017.11.275. Epub 2017 Dec 2.

Abstract

Most T1 colorectal cancers treated by radical surgery can now be cured by endoscopic submucosal dissection. Although 70%-80% of T1 colorectal cancers are classified as high risk, <16% of these patients actually have lymph node metastases. Biomarkers are needed to identify patients with T1 cancers with the highest risk of metastasis, to prevent unnecessary radical surgery. We collected data from The Cancer Genome Atlas and identified 5 microRNAs (MIR32, MIR181B, MIR193B, MIR195, and MIR411) with significant changes in expression in T1 and T2 colorectal cancers with vs without lymph node metastases. Levels of the 5 microRNAs identified patients with lymph node invasion by T1 or T2 cancers with an area under the receiver operating characteristic curve (AUROC) value of 0.84. We validated these findings in 2 cohorts of patients with T1 cancers, using findings from histology as the reference. The 5-microRNA signature identified T1 cancers with lymph node invasion in cohort 1 with an AUROC value of 0.83, and in cohort 2 with an AUROC value of 0.74. When we analyzed biopsy samples from untreated patients, the 5-microRNA signature identified cancers with lymph node metastases with an AUROC value of 0.77. The 5-microRNA therefore identifies high-risk T1 colorectal cancers with a greater degree of accuracy than currently used pathologic features.

摘要

目前,大多数接受根治性手术治疗的T1期结直肠癌可通过内镜黏膜下剥离术治愈。尽管70%-80%的T1期结直肠癌被归类为高风险,但这些患者中实际发生淋巴结转移的不到16%。需要生物标志物来识别T1期癌症中转移风险最高的患者,以避免不必要的根治性手术。我们从癌症基因组图谱中收集数据,确定了5种微小RNA(MIR32、MIR181B、MIR193B、MIR195和MIR411),其在有或无淋巴结转移的T1期和T2期结直肠癌中的表达有显著变化。这5种微小RNA的水平可识别T1期或T2期癌症发生淋巴结侵犯的患者,受试者工作特征曲线(AUROC)下面积值为0.84。我们以组织学结果为参考,在2组T1期癌症患者中验证了这些发现。这5种微小RNA特征在队列1中识别出发生淋巴结侵犯的T1期癌症,AUROC值为0.83,在队列2中AUROC值为0.74。当我们分析未经治疗患者的活检样本时,这5种微小RNA特征识别出发生淋巴结转移的癌症,AUROC值为0.77。因此,这5种微小RNA识别高风险T1期结直肠癌的准确性高于目前使用的病理特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f3/5847452/96bc9ac55706/nihms925404f1.jpg

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