Abstract
Esophageal cancer (EC) is a common malignant tumor in the digestive system which is often diagnosed at the middle and late stages. Noninvasive diagnosis using circulating miRNA as biomarkers enables accurate detection of early-stage EC to reduce mortality. We built a diagnostic signature consisting of four miRNA pairs for the early detection of EC using individualized Pairwise Analysis of Gene Expression (iPAGE). Profiling of miRNA expression identified 496 miRNA pairs with significant relative expression change. Four miRNA pairs consistently selected from LASSO were used to construct the final diagnostic model. The performance of the signature was validated using two independent datasets, yielding both AUCs and PRCs over 0.99. Furthermore, precision, recall, and F-score were also evaluated for clinical application, when a fixed threshold is given, resulting in all the scores are larger than 0.92 in the training set, test set, and two validation sets. Our results suggested that the 4-miRNA signature is a new biomarker for the early diagnosis of patients with EC. The clinical use of this signature would have improved the detection of EC for earlier therapy and more favorite prognosis.
Highlights
Epidemiological data have indicated that esophageal cancer (EC), a common malignant tumor in the digestive system, is the sixth cause of tumor-related death, and is accompanied by an increasing incidence and mortality worldwide [1]
We found literature supported evidences showing that the four miRNA pairs are highly associated with Esophageal cancer (EC)
Our results revealed that miRNAs pairs may serve as potential biomarkers for EC diagnosis
Summary
Epidemiological data have indicated that esophageal cancer (EC), a common malignant tumor in the digestive system, is the sixth cause of tumor-related death, and is accompanied by an increasing incidence and mortality worldwide [1]. Despite the advances in surgical techniques and chemoradiotherapy strategies have extensively improved the prognosis of EC patients, EC remains a deadly cancer of the gastrointestinal tract. Non-coding RNAs (ncRNAs) regulate gene transcription and recently are emerging as a novel therapeutic targets and promising biomarkers for disease diagnosis and prognosis [7,8,9,10,11,12]. Numerous studies have indicated that miRNAs play as pivotal regulators in the tumorigenesis, progression, proliferation, and metastasis of various cancers, including EC [16, 17]. Despite many miRNAs potentially important to cancers are yet to be characterized, their expression patterns have shown their noninvasive diagnosis ability in detecting and monitoring cancer progression [18]
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