一项关于 microRNAs 作为肛门癌患者新的预后生物标志物的研究。

A study of microRNAs as new prognostic biomarkers in anal cancer patients.

机构信息

Department of Oncology, Haukeland University Hospital, Bergen, Norway; University of Bergen, Bergen Norway.

Department of Oncology, Haukeland University Hospital, Bergen, Norway.

出版信息

Acta Oncol. 2024 Jun 20;63:456-465. doi: 10.2340/1651-226X.2024.27976.

DOI:10.2340/1651-226X.2024.27976

PMID:38899393

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11332526/

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.

INTERPRETATION

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) 通过调控 50-60%的所有基因的 mRNA 来影响癌症的生长。我们根据目前的知识，首次对肛门癌患者的 microRNA 表达进行了全面分析，并探讨了其预后意义。

方法

本研究纳入了 2003 年 9 月至 2011 年 4 月期间接受根治性治疗的 29 例 T1-4N0-3M0 肛门癌患者。从新鲜冷冻组织中提取 RNA，并使用 NGS 进行测序。使用 R 包 DEseq2 识别差异表达的 microRNAs，终点为无进展生存期（TTP）和癌症特异性生存期（CSS）。

结果

有 5 个 microRNAs 与 5 年无进展生存率（PFS）显著相关：两个 microRNAs 的低表达与较高的 PFS 相关，miR-1246（100%比 55.6%，p=0.008）和 miR-135b-5p（92.9%比 59.3%，p=0.041）。另一方面，三个 microRNAs 的高表达与较高的 PFS 相关，miR-148a-3p（93.3%比 53.6%，p=0.025）、miR-99a-5p（92.9%比 57.1%，p=0.016）和 let-7c-3p（92.9%比 57.1%，p=0.016）。CSS 也记录了相应的发现。

结论

本研究鉴定了 5 个 microRNAs 作为肛门癌的预后标志物。miR-1246 和 miR-135b-5p 是癌基因 microRNAs（具有致癌基因效应的 microRNAs），而 miR-148a-3p、miR-99a-5p 和 let-7c-3p 在肛门癌患者中充当肿瘤抑制 microRNAs。