Department of Biostatistics, School of Public Health, Harbin Medical University, No. 157 Baojian Road, 150081, Harbin City, Heilongjiang Province, China.
Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Cancer Res Clin Oncol. 2023 Oct;149(13):12443-12457. doi: 10.1007/s00432-023-05130-1. Epub 2023 Jul 13.
Colon cancer (CC) is a cancer of the large intestine with high prevalence and poor prognosis. enhancer RNAs. Therefore, valuable tools or biomarkers for predicting patient status, directing clinical practice, and reducing overtreatment are needed. Enhancer RNAs (eRNAs), a class of noncoding RNAs transcribed from enhancers, have been shown to function as regulators of oncogene or tumor suppressor gene expression. The aim of our study was to explore the potential roles of eRNAs and their target enhancer-related genes (ERGs) in the prognosis of CC.
Selected CC cases (stage I-III) from The Cancer Genome Atlas database were used as a training set, and cases from the Gene Expression Omnibus were used as the validation set. ERGs associated with prognosis were screened through three steps: potential, candidate, and prognosis ERGs. Multivariate Cox proportional hazards analysis was used to identify independent prognostic factors, and a nomogram was created. Calibration curves were drawn by comparing predicted and observed survival probability. For validation, the calibration curves and ROC analysis were also applied to two external validation sets. The biological significance and clinical application of the genes obtained were investigated.
Based on the multiple tiers of strict screening, 11 prognostic ERGs were obtained, which were combined to obtain a prognosis signature. A compound nomogram integrating age, TNM classification, and the prognostic signature was constructed. The model was reliable in distinguishing the risk of patients with stage I-III CC, with AUCs of 0.78 and 0.70 at 5 and 7 years, respectively. There was good reproducibility in calibration curves. The prognostic model also yielded good prediction capability in the validation sets.
In this study, the usefulness and specificity of the ERGs in prognosis were described, which should be considered a key feature in the clinical guidance of CC patients with early stage. We concluded that the major implications of the eRNAs and ERGs should be valued, which would be an emerging hallmark in the prognosis of cancer.
结肠癌（CC）是一种高发且预后不良的大肠癌症。增强子 RNA（eRNAs）是一类从增强子转录而来的非编码 RNA，已被证明可作为调节癌基因或肿瘤抑制基因表达的调节剂。本研究旨在探讨 eRNAs 及其靶增强子相关基因（ERGs）在 CC 预后中的潜在作用。
从癌症基因组图谱数据库中选择 CC 病例（I-III 期）作为训练集，从基因表达综合数据库中选择病例作为验证集。通过三个步骤筛选与预后相关的 ERGs：潜在、候选和预后 ERGs。多变量 Cox 比例风险分析用于识别独立的预后因素，并创建了一个列线图。通过比较预测和观察的生存概率来绘制校准曲线。为了验证，还将校准曲线和 ROC 分析应用于两个外部验证集。研究了获得的基因的生物学意义和临床应用。
基于严格的多层筛选，获得了 11 个预后 ERGs，将其组合以获得预后特征。构建了一个综合年龄、TNM 分类和预后特征的复合列线图模型。该模型在区分 I-III 期 CC 患者的风险方面具有可靠性，5 年和 7 年的 AUC 分别为 0.78 和 0.70。校准曲线具有良好的可重复性。该预后模型在验证集中也具有良好的预测能力。
本研究描述了 ERGs 在预后中的有用性和特异性，这应被视为指导早期 CC 患者临床治疗的关键特征。我们得出结论，eRNAs 和 ERGs 的主要意义应该得到重视，这将是癌症预后的一个新兴标志。
