唾液细胞外 microRNAs 用于食管癌的早期检测和预后：一项临床研究。

Salivary Extracellular MicroRNAs for Early Detection and Prognostication of Esophageal Cancer: A Clinical Study.

机构信息

Department of Urology, Guangdong Second Provincial General Hospital, Faculty of Medical Science and Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong, China; Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, China.

Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, China; Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Graduate School, Shantou University Medical College, Shantou, Guangdong, China.

出版信息

Gastroenterology. 2023 Oct;165(4):932-945.e9. doi: 10.1053/j.gastro.2023.06.021. Epub 2023 Jul 1.

DOI:10.1053/j.gastro.2023.06.021

PMID:37399999

Abstract

BACKGROUND & AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a microRNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.

METHODS

Salivary EVP miRNA expression was profiled in a pilot cohort (n = 54) using microarray. Area under the receiver operator characteristic curve (AUROC) and least absolute shrinkage and selector operation regression analyses were used to prioritize miRNAs that discriminated patients with ESCC from controls. Using quantitative reverse transcription polymerase chain reaction, the candidates were measured in a discovery cohort (n = 72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n = 342) and validated in an internal cohort (n = 207) and an external cohort (n = 226).

RESULTS

The microarray analysis identified 7 miRNAs for distinguishing patients with ESCC from control subjects. Because 1 was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified patients with all-stage ESCC in the training cohort (AUROC = 0.968) and was successfully validated in 2 independent cohorts. Importantly, this signature could distinguish patients with early-stage (stage Ⅰ/Ⅱ) ESCC from control subjects in the training cohort (AUROC = 0.969, sensitivity = 92.00%, specificity = 89.17%) and internal (sensitivity = 90.32%, specificity = 91.04%) and external (sensitivity = 91.07%, specificity = 88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.

CONCLUSIONS

The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.

摘要

背景与目的

早期发现食管鳞状细胞癌（ESCC）有助于进行根治性治疗。本研究旨在建立一种基于唾液细胞外囊泡和颗粒（EVP）的微小 RNA（miRNA）特征，用于早期 ESCC 的检测和预后判断。

方法

采用微阵列技术对一个先导队列（n=54）的唾液 EVP miRNA 表达谱进行了分析。使用受试者工作特征曲线（AUROC）下面积和最小绝对收缩和选择算子回归分析，以优先选择区分 ESCC 患者与对照者的 miRNA。采用定量逆转录聚合酶链反应（qRT-PCR）在发现队列（n=72）和细胞系中测量候选 miRNA。利用训练队列（n=342）构建了生物标志物的预测模型，并在内部队列（n=207）和外部队列（n=226）中进行了验证。

结果

微阵列分析确定了 7 个 miRNA 用于区分 ESCC 患者和对照者。由于在发现队列和细胞系中并非总能检测到 1 个 miRNA，因此将其他 6 个 miRNA 组合成一个面板。该面板的特征在训练队列中准确地识别出所有阶段的 ESCC 患者（AUROC=0.968），在 2 个独立队列中得到了成功验证。重要的是，该特征可以在训练队列中区分早期（Ⅰ/Ⅱ期）ESCC 患者和对照者（AUROC=0.969，敏感性=92.00%，特异性=89.17%）以及内部（敏感性=90.32%，特异性=91.04%）和外部（敏感性=91.07%，特异性=88.06%）验证队列。此外，建立了基于该面板的预后特征，并有效地预测了具有不良无进展生存期和总生存期的高危病例。