Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California; Department of Surgery, Nara Medical University, Nara, Japan.
Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas; Gastroenterology Department, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB) and Centro de Investigación Biomédica de Canarias (CIBICAN), Departamento de Medicina Interna, Universidad de La Laguna, Santa Cruz de Tenerife, Tenerife, Spain.
Gastroenterology. 2022 Nov;163(5):1242-1251.e2. doi: 10.1053/j.gastro.2022.06.089. Epub 2022 Jul 16.
BACKGROUND & AIMS: Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC.
A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays.
In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P < .001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity.
Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.
与晚发性结直肠癌（CRC）相比，早发性结直肠癌（EOCRC）具有明显的临床和分子特征，且生存预后较差。尽管 EOCRC 的发病率正在上升，但目前的 CRC 筛查策略在 EOCRC 的诊断性能方面存在多种局限性。鉴于这一临床挑战，有必要寻找用于检测 EOCRC 的新型稳健生物标志物。本研究旨在开发用于诊断 EOCRC 患者的循环微小 RNA（miRNA）特征。
通过分析大型公开的非编码 RNA 表达谱数据集（GSE115513），采用系统的发现方法。鉴定了一组 miRNA，然后使用定量逆转录聚合酶链反应检测，在 2 个独立队列（n=149）的 EOCRC 患者的血液样本中（与对照组 n=110）以及术前/术后血浆标本（n=22）中对其进行验证。
在发现阶段，发现 4 种 miRNA 在血液样本中表达。这 4 种 miRNA 的组合特征（miR-193a-5p、miR-210、miR-513a-5p 和 miR-628-3p）在训练队列中对 EOCRC 的识别产生了 0.92（95%置信区间，0.85-0.96）的曲线下面积。然后在独立验证队列中确认了 miRNA 面板的性能（曲线下面积为 0.88；95%置信区间，0.82-0.93）。此外，miRNA 面板可准确识别早期 EOCRC 患者（P<.001）。手术后血浆标本中 miRNA 的表达降低表明其具有肿瘤特异性。
我们用于诊断 EOCRC 的新型 miRNA 特征有可能以高精度识别 EOCRC 患者，从而有可能在非侵入性诊断 EOCRC 中进行临床应用。
