Abstract

Background MicroRNAs (miRNAs) have been applied to cancer diagnosis taking into account their role in tumorigenesis. The main purpose of our study was to confirm the possibility of using miRNAs as noninvasive biomarkers for stomach adenocarcinoma (STAD) diagnosis. Methods A total of 246 participants (130 STAD patients and 116 healthy controls (HCs)) were enrolled in this 3-phase study. Five STAD pools and 3 HC pools (with 4 participants in each pool) were used for the screening of the 28 miRNAs using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The training phase (30 STAD patients vs. 24 HCs) and validation phase (80 STAD patients vs. 80 HCs) were used to further verify the identity of these miRNAs. Kaplan–Meier survival analysis and bioinformatics analysis were also used. Results The expression levels of miR-125b-5p and miR-196a-5p were upregulated in STAD serum, compared with the HCs, while miR-1-3p and miR-149-5p showed the opposite result. A four-serum miRNA panel was constructed, and the area under the receiver operating characteristic curve (AUC) was found to be 0.892 (95% CI: 0.834 to 0.936, sensitivity = 86.25%, specificity = 78.75%). Only miR-125b-5p expression showed a significant difference between STAD patients and NCs in the survival analysis. The neurotrophin signaling pathway was associated with 4 miRNAs identified in STAD patients. Conclusion The four-serum miRNA panel has great potential to be used as a noninvasive biomarker for STAD diagnosis.

Highlights

  • Gastric cancer has been ranked third for the number of cancer-associated deaths globally. 1.2 million new cases of stomach cancer and 834,000 deaths were reported worldwide in 2016 [1]

  • 130 stomach adenocarcinoma (STAD) patients and 116 healthy controls (HCs) were enrolled in our experiment

  • We compared STAD patients with HCs who had no history of cancer or interferential diseases

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Summary

Introduction

Gastric cancer has been ranked third for the number of cancer-associated deaths globally. 1.2 million new cases of stomach cancer and 834,000 deaths were reported worldwide in 2016 [1]. If the opportunity to undergo surgery is missed, the median survival time of advanced-stage stomach adenocarcinoma (STAD) is only 9-10 months [5]. Concentrating on the early diagnosis of STAD could greatly improve the overall survival rate of gastric cancer patients [6]. The main diagnostic method used is endoscopy or surgical biopsy, which examined the gold standard for diagnosing STAD. The main purpose of our study was to confirm the possibility of using miRNAs as noninvasive biomarkers for stomach adenocarcinoma (STAD) diagnosis. The expression levels of miR-125b-5p and miR-196a-5p were upregulated in STAD serum, compared with the HCs, while miR-1-3p and miR-149-5p showed the opposite result. The four-serum miRNA panel has great potential to be used as a noninvasive biomarker for STAD diagnosis

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