Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma

Molecular Cancer

Shufeng Lei¹  Wei Wang²  Bingjian Lu³  Jiaqi Hu³  Lanyun Zhou³  Siqi Yang³  Mengyue Zheng³  Fenfen Wang³  Zimin Pan³  Yu Ma³  Yan Lu⁴  Weiguo Lu⁴  Liyuan Zhou⁵  Pengyuan Liu⁶  Penghong Song⁷ 

[1] Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, 215123, Suzhou, Jiangsu, China;Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, 310006, Hangzhou, Zhejiang, China;Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women’s Reproductive Health Key Laboratory of Zhejiang Province, Women’s Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China;Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women’s Reproductive Health Key Laboratory of Zhejiang Province, Women’s Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China;Cancer center, Zhejiang University, 310013, Hangzhou, Zhejiang, China;Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, 310016, Hangzhou, Zhejiang, China;Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, 310016, Hangzhou, Zhejiang, China;Cancer center, Zhejiang University, 310013, Hangzhou, Zhejiang, China;Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, 310013, Hangzhou, Zhejiang, China;

关键词: Endometrial cancer;    Liquid biopsy;    Plasma-derived exosomal miRNA;    ddPCR;    Cancer diagnosis;    Early detection;   

DOI  :  10.1186/s12943-021-01352-4

来源: Springer

【 摘 要 】

Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.

【 授权许可】

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