Department of Biotechnology, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India.
North Terrace Campus, University of Adelaide, Adelaide, SA, Australia.
Mol Diagn Ther. 2019 Feb;23(1):65-82. doi: 10.1007/s40291-019-00381-6.
Findings from observational clinical studies examining the relationship between biomarker expression and theranosis in colorectal cancer (CRC) have been conflicting.
We conducted this systematic review and meta-analysis to summarise the existing evidence to demonstrate the involvement of microRNAs (miRNAs) in chemoresistance and sensitivity in CRC through drug genetic pathways.
Using PRISMA guidelines, we systematically searched PubMed and Science Direct for relevant studies that took place between 2012 and 2017. A random-effects model of meta-analysis was applied to evaluate the pooled effect size of hazard ratios (HRs) across the included studies. Cochran's Q test and the I statistic were used to detect heterogeneity. A funnel plot was used to assess potential publication bias.
Of the 4700 studies found, 39 studies comprising 2822 patients with CRC met the inclusion criteria. The included studies used one or a combination of 14 chemotherapy drugs, including 5-fluorouracil and oxaliplatin. Of the 60 miRNAs, 28 were associated with chemosensitivity, 20 with chemoresistance, and one with differential expression and radiosensitivity; ten miRNAs were not associated with any impact on chemotherapy. The results outline the importance of 34 drug-regulatory pathways of chemoresistance and sensitivity in CRC. The mean effect size was 0.689 (95% confidence interval 0.428-1.110), indicating that the expression of miRNAs decreased the likelihood of death by about 32%.
Studies have consistently shown that multiple miRNAs could act as clinical predictors of chemoresistance and sensitivity. An inclusion of supplementary miRNA estimation in CRC routine practice needs to be considered to evaluate the efficacy of chemotherapy after confirming our findings with large-scale prospective cohort studies.
CRD42017082196.
观察性临床研究中关于生物标志物表达与结直肠癌（CRC）治疗之间关系的研究结果存在矛盾。
本系统评价和荟萃分析旨在总结现有证据，通过药物遗传途径证明 microRNAs（miRNAs）在 CRC 化疗耐药和敏感性中的作用。
使用 PRISMA 指南，我们系统地检索了 PubMed 和 Science Direct 数据库，以获取 2012 年至 2017 年期间发表的相关研究。采用随机效应模型荟萃分析评估纳入研究中风险比（HRs）的合并效应大小。Cochran's Q 检验和 I 统计量用于检测异质性。漏斗图用于评估潜在的发表偏倚。
在 4700 项研究中，有 39 项研究共纳入 2822 例 CRC 患者符合纳入标准。纳入的研究使用了一种或多种 14 种化疗药物，包括 5-氟尿嘧啶和奥沙利铂。在 60 个 miRNA 中，有 28 个与化疗敏感性相关，20 个与化疗耐药性相关，1 个与差异表达和放射敏感性相关，10 个 miRNA 与化疗无任何影响相关。结果概述了 CRC 中 34 种化疗耐药和敏感性相关药物调节途径的重要性。平均效应大小为 0.689（95%置信区间 0.428-1.110），表明 miRNA 的表达使死亡的可能性降低了约 32%。
研究一致表明，多种 miRNAs 可以作为化疗耐药和敏感性的临床预测因子。在通过大规模前瞻性队列研究证实我们的发现后，需要考虑在 CRC 常规实践中纳入补充 miRNA 评估，以评估化疗的疗效。
PROSPERO 注册号：CRD42017082196。
