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CCR:微RNA表达异常降低胰腺导管腺癌(PDAC)患者生存率

2011-11-28 我要评论0

 《临床癌症研究》杂志11月23日在线发表的一项研究表明,胰腺导管腺癌(PDAC)组织微RNA(miR)的表达显著改变。一些miR的异常表达,包括miR-21过度表达和miR-34a表达不足与患者生存率下降独立相关。

  该研究分析了48例胰腺导管腺癌组织中miR表达情况,评估了其与肿瘤分期、淋巴结状态和复发部位的关联,并在另外24例患者中,验证了经挑选的可能的具有预后意义的miR。

  结果显示,在初始48例患者中,miR-21高表达以及miR-34a和miR-30d低表达与患者生存状况较差相关。在另外24例患者中,研究确认miR-21 和miR-34a表达与总生存显著相关。

  相关链接:MicroRNA molecular profiles associated with diagnosis, clinicopathological criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma

摘要:

Purpose:MicroRNAs (miRNAs) have potential as diagnostic and prognostic biomarkers and as therapeutic targets in cancer. We sought to establish the relationship between miRNA expression and clinicopathological parameters, including prognosis, in pancreatic ductal adenocarcinoma (PDAC). Experimental Design:Global miRNA microarray expression profiling of prospectively collected fresh-frozen PDAC tissue was performed on an initial test cohort of 48 patients, who had undergone pancreaticoduodenectomy between 2003 and 2008 at a single institution. We evaluated association with tumor stage, lymph node status, site of recurrence in addition to overall survival using Cox-regression multivariate analysis. Validation of selected potentially prognostic miRNAs was performed in a separate cohort of 24 patients. Results:miRNA profiling identified expression signatures associated with PDAC, lymph node involvement, high tumor grade, and 20 microRNAs were associated with overall survival. In the initial cohort of 48 PDAC patients, high expression of miR-21 (Hazard ratio (HR): 3.22, 95% Confidence Interval (CI):1.21-8.58) and reduced expression of miR-34a (HR 0.15, 95%CI: 0.06-0.37) and miR-30d (HR:0.30, 95%CI:0.12-0.79) were associated with poor overall survival following resection independent of clinical covariates. In a further validation set of 24 patients miR-21 and miR-34a expression again significantly correlated with overall survival (P = 0.031 and P = 0.001). Conclusions:Expression patterns of microRNAs are significantly altered in PDAC. Aberrant expression of a number of miRNAs were independently associated with reduced survival including over-expression of miR-21 and under-expression of miR-34a.



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