Romero-Lorca Alicia, Novillo Apolonia, Gaibar María, Gilsanz María Fuencisla, Galán Miguel, Beltrán Laura, Antón Beatriz, Malón Diego, Moreno Amalia, Fernández-Santander Ana
Biomedical and Health Sciences Faculty, Universidad Europea de Madrid, Madrid, 28670, Spain.
Department of Oncology, University Hospital of Fuenlabrada, Madrid, 28942, Spain.
Pharmgenomics Pers Med. 2021 Sep 29;14:1263-1273. doi: 10.2147/PGPM.S313594. eCollection 2021.
Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor A. It is currently used in combination with chemotherapy to treat metastatic colorectal cancer. This therapy is not equally effective in every patient; in some, mechanisms of resistance arise that remain poorly understood. The aim of the present work was to determine whether the expression of 26 miRNAs could be associated with the effectiveness of bevacizumab plus chemotherapy, with progression-free survival (PFS), and with overall survival (OS) in metastatic colorectal cancer.
Paraffin-embedded biopsies from 76 patients with metastatic colorectal cancer were collected to isolate miRNAs. The expression of 26 miRNAs was analyzed by quantitative RT-PCR. For the purpose of analysis, patients were classified as either "responders" (PFS ≥6 months since beginning treatment) or "non-responders" (PFS <6 months). For the analysis of PFS and OS, patients were classified into two groups using the median gene expression value as the cut-off point ("high" [≥50% percentile] or "low" [<50% percentile]). Time-to-event data were analyzed using the Kaplan-Meier method and compared by the log rank test. Cox regression was used to estimate hazard ratios (HR) and their 95% confidence intervals.
miR-7-5p and miR-10a-5p were more strongly expressed in non-responders than responders (p=0.049 and p=0.043, respectively), and OS was poorer in patients showing these higher expression levels (HR=2.54, 95% CI 1.42-4.55, p=0. 001, and HR=1.81, 95% CI 1.02-3.20, p=0.039, respectively). The overexpression of miR-143-3p, however, was associated with a better prognosis and significantly better PFS (HR=0.57; 95% CI: 0.33-0.96; p=0.033).
High expression values for miR-7-5p and miR-10a-5p might be considered markers of a poorer prognosis in patients with metastatic colorectal cancer treated with bevacizumab plus chemotherapy, while the same for miR-143-3p might be a marker of better outcomes.
贝伐单抗是一种与血管内皮生长因子A结合的单克隆抗体。它目前与化疗联合用于治疗转移性结直肠癌。这种疗法并非对每个患者都同样有效；在一些患者中，出现了耐药机制，对此仍知之甚少。本研究的目的是确定26种微小RNA（miRNA）的表达是否与贝伐单抗加化疗的疗效、无进展生存期（PFS）以及转移性结直肠癌的总生存期（OS）相关。
收集76例转移性结直肠癌患者的石蜡包埋活检组织以分离miRNA。通过定量逆转录聚合酶链反应（RT-PCR）分析26种miRNA的表达。为了进行分析，将患者分为“反应者”（自开始治疗起PFS≥6个月）或“无反应者”（PFS<6个月）。为了分析PFS和OS，以基因表达中位数作为分界点（“高”[≥第50百分位数]或“低”[<第50百分位数]）将患者分为两组。采用Kaplan-Meier法分析生存时间数据，并通过对数秩检验进行比较。使用Cox回归估计风险比（HR）及其95%置信区间。
miR-7-5p和miR-10a-5p在无反应者中的表达比反应者更强（分别为p=0.049和p=0.043），并且在这些表达水平较高的患者中OS较差（HR=2.54，95%CI 1.42-4.55，p=0.001，以及HR=1.81，95%CI 1.02-3.20，p=0.039）。然而，miR-143-3p的过表达与较好的预后和显著更好的PFS相关（HR=0.57；95%CI：0.33-0.96；p=0.033）。
对于接受贝伐单抗加化疗治疗的转移性结直肠癌患者，miR-7-5p和miR-10a-5p的高表达值可能被视为预后较差的标志物，而miR-143-3p的高表达值可能是预后较好的标志物。
