GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma

BMC Cancer

Sun A Kim¹  Jeong Hoon Lee²  Yu Rang Park²  Moon Jae Chung³  Hee Seung Lee³  Jung Hyun Jo³  Si Young Song³  Soo Been Park⁴  Chanyang Kim⁴  Dawoon E. Jung⁴ 

[1] Cowell Biodigm Co., Ltd, Seoul, South Korea;Department of Biomedical Systems Informatics, Yonsei University College of Medicine, 03722, Seoul, South Korea;Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, 03722, Seoul, South Korea;Institute of Gastroenterology, Yonsei University College of Medicine, 03722, Seoul, South Korea;Institute of Gastroenterology, Yonsei University College of Medicine, 03722, Seoul, South Korea;

关键词: Pancreatic cancer;    Cancer stem cell;    Biomarker;    Glutaredoxin 3;    GLRX3;    Stemness;   

DOI  :  10.1186/s12885-021-08898-y

来源: Springer

【 摘 要 】

BackgroundCancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear.MethodIn this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication.ResultsPDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19–9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19–9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery.ConclusionOverall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.

【 授权许可】

CC BY