Abstract：
BACKGROUND: MicroRNA (MiR) influences the growth of cancer by regulation of mRNA for 50-60% of all genes. We present as per our knowledge the first global analysis of microRNA expression in anal cancer patients and their prognostic impact.
METHODS: Twenty-nine patients with T1-4 N0-3 M0 anal cancer treated with curative intent from September 2003 to April 2011 were included in the study. RNA was extracted from fresh frozen tissue and sequenced using NGS. Differentially expressed microRNAs were identified using the R-package DEseq2 and the endpoints were time to progression (TTP) and cancer specific survival (CSS).
RESULTS: Five microRNAs were significantly associated with 5-year progression free survival (PFS): Low expression of two microRNAs was associated with higher PFS, miR-1246 (100% vs. 55.6%, p = 0.008), and miR-135b-5p (92.9% vs. 59.3%, p = 0.041). On the other hand, high expressions of three microRNAs were associated with higher PFS, miR-148a-3p (93.3% vs. 53.6%, p = 0.025), miR-99a-5p (92.9% vs. 57.1%, p = 0.016), and let-7c-3p (92.9% vs. 57.1%, p = 0.016). Corresponding findings were documented for CSS.
CONCLUSIONS: Our study identified five microRNAs as prognostic markers in anal cancer. MiR-1246 and microRNA-135b-5p were oncoMiRs (miRs with oncogene effects), while miR-148a-3p, miR- 99a-5p, and let-7c-3p acted as tumour suppressors in anal cancer patients.
METHODS: Twenty-nine patients with T1-4 N0-3 M0 anal cancer treated with curative intent from September 2003 to April 2011 were included in the study. RNA was extracted from fresh frozen tissue and sequenced using NGS. Differentially expressed microRNAs were identified using the R-package DEseq2 and the endpoints were time to progression (TTP) and cancer specific survival (CSS).
RESULTS: Five microRNAs were significantly associated with 5-year progression free survival (PFS): Low expression of two microRNAs was associated with higher PFS, miR-1246 (100% vs. 55.6%, p = 0.008), and miR-135b-5p (92.9% vs. 59.3%, p = 0.041). On the other hand, high expressions of three microRNAs were associated with higher PFS, miR-148a-3p (93.3% vs. 53.6%, p = 0.025), miR-99a-5p (92.9% vs. 57.1%, p = 0.016), and let-7c-3p (92.9% vs. 57.1%, p = 0.016). Corresponding findings were documented for CSS.
CONCLUSIONS: Our study identified five microRNAs as prognostic markers in anal cancer. MiR-1246 and microRNA-135b-5p were oncoMiRs (miRs with oncogene effects), while miR-148a-3p, miR- 99a-5p, and let-7c-3p acted as tumour suppressors in anal cancer patients.
摘要：
背景：MicroRNA（MiR）通过调节所有基因中50-60％的mRNA来影响癌症的生长。根据我们的知识，我们首次对肛门癌患者的microRNA表达及其预后影响进行了全球分析。
方法：将2003年9月至2011年4月29例T1-4N0-3M0肛门癌患者纳入研究。从新鲜冷冻组织中提取RNA并使用NGS测序。使用R-包装DEseq2鉴定差异表达的微小RNA,并且终点是进展时间(TTP)和癌症特异性存活(CSS)。
结果：5个微小RNA与5年无进展生存期（PFS）显著相关：2个微小RNA的低表达与较高的PFS相关，miR-1246（100%vs.55.6%,p=0.008),和miR-135b-5p（92.9%vs.59.3%,p=0.041)。另一方面,三种microRNAs的高表达与较高的PFS相关，miR-148a-3p（93.3%vs.53.6%,p=0.025),miR-99a-5p（92.9%vs.57.1%,p=0.016),和let-7c-3p（92.9%与57.1%,p=0.016)。记录了CSS的相应发现。
结论：我们的研究确定了五种microRNA作为肛门癌的预后标志物。MiR-1246和microRNA-135b-5p是原癌MiR（具有癌基因效应的miR），而miR-148a-3p，miR-99a-5p,let-7c-3p在肛门癌患者中充当肿瘤抑制因子。
方法：将2003年9月至2011年4月29例T1-4N0-3M0肛门癌患者纳入研究。从新鲜冷冻组织中提取RNA并使用NGS测序。使用R-包装DEseq2鉴定差异表达的微小RNA,并且终点是进展时间(TTP)和癌症特异性存活(CSS)。
结果：5个微小RNA与5年无进展生存期（PFS）显著相关：2个微小RNA的低表达与较高的PFS相关，miR-1246（100%vs.55.6%,p=0.008),和miR-135b-5p（92.9%vs.59.3%,p=0.041)。另一方面,三种microRNAs的高表达与较高的PFS相关，miR-148a-3p（93.3%vs.53.6%,p=0.025),miR-99a-5p（92.9%vs.57.1%,p=0.016),和let-7c-3p（92.9%与57.1%,p=0.016)。记录了CSS的相应发现。
结论：我们的研究确定了五种microRNA作为肛门癌的预后标志物。MiR-1246和microRNA-135b-5p是原癌MiR（具有癌基因效应的miR），而miR-148a-3p，miR-99a-5p,let-7c-3p在肛门癌患者中充当肿瘤抑制因子。
