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Open Access 01-12-2021 | Pancreatic Cancer | Research

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

Authors: 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

Published in: BMC Cancer | Issue 1/2021

Abstract

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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Title: GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma
Authors: 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
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Pancreatic Cancer
Pancreatic Cancer
Biomarkers
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08898-y

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Method

Results

Conclusion

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer