生物谷報(bào)道:根據(jù)1月30日的《美國(guó)醫(yī)學(xué)協(xié)會(huì)期刊》(JAMA)上的一則研究顯示,初步的研究發(fā)現(xiàn),,某些microRNA表達(dá)形式與結(jié)腸癌的不良的存活率及治療效果有關(guān)聯(lián),。
小RNA是由18-25個(gè)核苷酸組成的非編碼RNA(核糖核酸)分子,,人們發(fā)現(xiàn)它們參與多種類型的細(xì)胞內(nèi)過程的調(diào)節(jié),,而且還可能對(duì)癌細(xì)胞的發(fā)展扮演著某種角色,。根據(jù)原文背景資料介紹,,microRNA的預(yù)后潛力已經(jīng)在慢性淋巴細(xì)胞性白血病,、肺癌及胰腺癌中得到證實(shí)。但是現(xiàn)在尚無有關(guān)研究來評(píng)估m(xù)icroRNA的表達(dá)形式與結(jié)腸癌預(yù)后或治療結(jié)果的相關(guān)性,。
美國(guó)國(guó)立癌癥研究所(NCI)的Aaron J. Schetter與Curtis C. Harris及其同僚對(duì)結(jié)腸腫瘤的microRNA表達(dá)譜進(jìn)行了評(píng)估,,并將其與非腫瘤組織進(jìn)行配對(duì)比較,以研究它們?cè)诮Y(jié)腸癌的腫瘤形成,、診斷及治療效果方面可能起到的作用,。這項(xiàng)研究包括84名來自馬里蘭州的病人,而其相關(guān)性則在第二個(gè)有113名來自香港的獨(dú)立病人小組中得到確認(rèn),。
研究人員說,,“我們發(fā)現(xiàn)在結(jié)腸腫瘤與配對(duì)的非腫瘤組織之間存在著microRNA表達(dá)形式上的系統(tǒng)差別。miR-21高度表達(dá)的腫瘤與不良存活率及輔助化療反應(yīng)不佳之間存在著相關(guān)性,。這種相關(guān)性在2個(gè)獨(dú)立的病患集群中得到驗(yàn)證,,而且它與腫瘤的分期及其他的臨床協(xié)變量無關(guān),。這表明miR-21 可能可以作為一種用于結(jié)腸腺癌與包括治療反應(yīng)在內(nèi)的存活預(yù)后之實(shí)用性診斷生物標(biāo)記。”(生物谷援引:EurekAlert! 中文版)
生物谷推薦原始出處:
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).