JAMA:小RNA表达形式与结肠癌不良预后相关-自主发布-资讯-生物在线

JAMA:小RNA表达形式与结肠癌不良预后相关

作者:上海研辉生物科技有限公司 2011-08-08T00:00 (访问量:2279)

生物谷报道:根据1月30日的《美国医学协会期刊》(JAMA)上的一则研究显示,初步的研究发现,某些microRNA表达形式与结肠癌的不良的存活率及治疗效果有关联。

小RNA是由18-25个核苷酸组成的非编码RNA(核糖核酸)分子,人们发现它们参与多种类型的细胞内过程的调节,而且还可能对癌细胞的发展扮演着某种角色。根据原文背景资料介绍,microRNA的预后潜力已经在慢性淋巴细胞性白血病、肺癌及胰腺癌中得到证实。但是现在尚无有关研究来评估microRNA的表达形式与结肠癌预后或治疗结果的相关性。

美国国立癌症研究所(NCI)的Aaron J. Schetter与Curtis C. Harris及其同僚对结肠肿瘤的microRNA表达谱进行了评估,并将其与非肿瘤组织进行配对比较,以研究它们在结肠癌的肿瘤形成、诊断及治疗效果方面可能起到的作用。这项研究包括84名来自马里兰州的病人,而其相关性则在第二个有113名来自香港的独立病人小组中得到确认。

研究人员说,“我们发现在结肠肿瘤与配对的非肿瘤组织之间存在着microRNA表达形式上的系统差别。miR-21高度表达的肿瘤与不良存活率及辅助化疗反应不佳之间存在着相关性。这种相关性在2个独立的病患集群中得到验证,而且它与肿瘤的分期及其他的临床协变量无关。这表明miR-21 可能可以作为一种用于结肠腺癌与包括治疗反应在内的存活预后之实用性诊断生物标记。”(生物谷援引:EurekAlert! 中文版)

生物谷推荐原始出处:

JAMA,Vol. 299 No. 4, January 30, 2008

MicroRNA Expression Profiles Associated With Prognosis and Therapeutic Outcome in Colon Adenocarcinoma

Aaron J. Schetter, PhD, MPH; Suet Yi Leung, MD; Jane J. Sohn, PhD; Krista A. Zanetti, PhD, MPH; Elise D. Bowman, MS; Nozomu Yanaihara, MD, PhD; Siu Tsan Yuen, MD; Tsun Leung Chan, MD; Dora L. W. Kwong, MD; Gordon K. H. Au, MD; Chang-Gong Liu, PhD; George A. Calin, MD, PhD; Carlo M. Croce, MD; Curtis C. Harris, MD

JAMA. 2008;299(4):425-436.

Context MicroRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. No study has evaluated the association between microRNA expression patterns and colon cancer prognosis or therapeutic outcome.

Objective To identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome.

Design, Setting, and Patients MicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on a US test cohort of 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We evaluated associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy. Associations were validated in a second, independent Chinese cohort of 113 patients recruited between 1991 and 2000, using quantitative reverse transcription polymerase chain reaction assays. The final date of follow-up was December 31, 2005, for the Maryland cohort and August 16, 2004, for the Hong Kong cohort.

Main Outcome Measures MicroRNAs that were differentially expressed in tumors and microRNA expression patterns associated with survival using cancer-specific death as the end point.

RESULTS Thirty-seven microRNAs were differentially expressed in tumors from the test cohort. Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P < .001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P < .001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells. The 5-year cancer-specific survival rate was 57.5% for the Maryland cohort and was 49.5% for the Hong Kong cohort. High miR-21 expression was associated with poor survival in both the training (hazard ratio, 2.5; 95% confidence interval, 1.2-5.2) and validation cohorts (hazard ratio, 2.4; 95% confidence interval, 1.4-3.9), independent of clinical covariates, including TNM staging, and was associated with a poor therapeutic outcome.

Conclusions Expression patterns of microRNAs are systematically altered in colon adenocarcinomas. High miR-21 expression is associated with poor survival and poor therapeutic outcome.


Author Affiliations: Laboratory of Human Carcinogenesis, Center for Cancer Research (Drs Schetter, Sohn, Zanetti, Yanaihara, and Harris and Ms Bowman) and Cancer Prevention Fellowship Program, Office of Preventive Oncology (Drs Schetter and Zanetti), National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Departments of Pathology (Drs Leung, Yuen, and Chan) and Clinical Oncology (Drs Kwong and Au), University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong; Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio (Drs Liu and Croce); and Department of Experimental Therapeutics, M. D. Anderson Cancer Center, Houston, Texas (Dr Calin).

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