Abstract

BackgroundGastrointestinal tumors are a leading cause of mortality worldwide. As shown in our previous study, miR-1290 is overexpressed in colorectal cancer (CRC) and promotes tumor progression. We therefore aimed to explore the potential of circulating miR-1290 as a biomarker for gastrointestinal cancer.MethodsA serum miRNA sequencing analysis was performed. Then, circulating miRNA detection technologies were established. The expression of miR-1290 was analyzed in gastrointestinal tumor cell lines and culture supernatants. Expression levels of circulating miR-1290 in clinical samples were examined. Associations between miR-1290 expression and clinicopathologic characteristics were analyzed. Xenograft models were generated to assess the fluctuation in serum miR-1290 levels during disease progression.ResultsThrough miRNA sequencing, we identified that miR-1290 was overexpressed in serum samples from patients with CRC. We confirmed that human gastrointestinal tumor cells express and secrete miR-1290. The circulating miR-1290 levels was up-regulated in patients with pancreatic cancer (PC) (p < 0.01), CRC (p < 0.05), and gastric cancer (GC) (p < 0.01). High miR-1290 expression levels were associated with tumor size, lymphatic invasion, vascular invasion, distant metastasis, tumor differentiation and AJCC stage in patients with PC and CRC. The area under the curve (AUC) was 0.8857 in patients with PC, with 60.9% sensitivity and 90.0% specificity. The AUC was 0.7852 in patients with CRC, with 42.0% sensitivity and 90.0% specificity. In patients with GC, the AUC was 0.6576, with 26.0% sensitivity and 90.0% specificity. The in vivo model verified that the circulating miR-1290 level was significantly increased after tumor formation and decreased after drug treatment.ConclusionsOur findings indicate that circulating miR-1290 is a potential biomarker for gastrointestinal cancer diagnosis and monitoring.

Highlights

  • Gastrointestinal tumors are a leading cause of mortality worldwide

  • MiR-1290 plays an important role in colorectal cancer (CRC) progression

  • As shown in the heatmap, hsa-miR-1290 was significantly overexpressed in serum from patients with CRC (Fig. 1d), suggesting that miR-1290 might be a potential biomarker for gastrointestinal tumors

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Summary

Introduction

Gastrointestinal tumors are a leading cause of mortality worldwide. As shown in our previous study, miR-1290 is overexpressed in colorectal cancer (CRC) and promotes tumor progression. Colorectal cancer (CRC) and pancreatic cancer (PC) have the highest incidence and mortality rates among gastrointestinal tumors in the United States [1]. In 2018, gastrointestinal (stomach, liver, and esophagus) cancerrelated deaths accounted for 36.4% of tumor-related deaths in China, while digestive cancer-related deaths comprised less than 5% of total cancer-related deaths in Western countries [3]. This difference may be related to the low early detection rate in China and the lack of uniformity of clinical treatment strategies in different regions. An effective screening method with high population coverage and compliance could have great clinical significance

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