Abstract
Circulating microRNAs (miRNAs) have been used as promising diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). We performed miRNA expression profiling using quantitative reverse transcription polymerase chain reaction (qRT‐PCR) based Exiqon panels from three ESCC pools and one normal control (NC) pool samples. Using qRT‐PCR, identified serum miRNAs were further confirmed in training (32 ESCC vs. 32 NCs) and testing stages (108 ESCC vs. 96 NCs). Consequently, five serum miRNAs (miR‐20b‐5p, miR‐28‐3p, miR‐192‐5p, miR‐223‐3p, and miR‐296‐5p) were significantly overexpressed in ESCC compared with NCs. The diagnostic value of the 5‐miRNA signature was validated by an external cohort (60 ESCC vs. 60 NCs). The areas under the receiver operating characteristic curve (ROC) of the 5‐miRNA signature were 0.753, 0.763, and 0.966 for the training, testing, and the external validation stages, respectively. The expression levels of the miRNAs were also determined in tissues, arterial serum, and exosomes. MiR‐20b‐5p, miR‐28‐3p, and miR‐192‐5p were significantly upregulated in ESCC tissues, while miR‐296‐5p was overexpressed in ESCC serum exosomes. In conclusion, we identified a 5‐miRNA signature in serum for the detection of ESCC.
Highlights
Esophageal cancer is the fourth leading cause of cancer death in China, with estimated 477,900 newly diagnosed cases and 375,000 deaths in 2015 [1]
In the present study, we focused on Esophageal squamous cell carcinoma (ESCC) patients and conducted a four-stage study to identify potential miRNAs for detecting ESCC by evaluating the expression of serum miRNAs based on qRT-P CR
To identify candidate serum miRNAs for ESCC diagnosis, the Exiqon miRCURY-Ready-to-Use polymerase chain reaction (PCR)-Human- panel-I + II-V1.M was conducted based on the qRT-PCR platform
Summary
Esophageal cancer is the fourth leading cause of cancer death in China, with estimated 477,900 newly diagnosed cases and 375,000 deaths in 2015 [1]. Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer, dominating almost 90% of esophageal cancer cases in China [2]. Most ESCC patients are diagnosed at a late stage due to lack of apparent symptoms and miss the optimal time for operation. Frequent imaging examinations, such as X-ray and computed tomography (CT), might cause radiation risk to patients, whereas endoscopy is invasive and mostly determined by the experience of operators [4]. Tumor markers such as squamous cell cancer antigen (SCC) and carcinoembryonic antigen (CEA) cannot show sufficient sensitivity and specificity [5]. It is important to identify novel and less invasive biomarkers for ESCC diagnosis
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