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

 Jung Hyun Jo  ;  Sun A Kim  ;  Jeong Hoon Lee  ;  Yu Rang Park  ;  Chanyang Kim  ;  Soo Been Park  ;  Dawoon E Jung  ;  Hee Seung Lee  ;  Moon Jae Chung  ;  Si Young Song 
 BMC CANCER, Vol.21(1) : 1241, 2021-11 
Journal Title
Issue Date
Biomarker ; Cancer stem cell ; GLRX3 ; Glutaredoxin 3 ; Pancreatic cancer ; Stemness
Background: Cancer 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.

Method: In 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.

Results: PDAC 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.

Conclusion: Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.
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1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Yu Rang(박유랑) ORCID logo https://orcid.org/0000-0002-4210-2094
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Lee, Hee Seung(이희승) ORCID logo https://orcid.org/0000-0002-2825-3160
Jung, Dawoon E.(정다운)
Chung, Moon Jae(정문재) ORCID logo https://orcid.org/0000-0002-5920-8549
Jo, Jung Hyun(조중현) ORCID logo https://orcid.org/0000-0002-2641-8873
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