Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 03722, South Korea.
BMC Cancer. 2021 Nov 18;21(1):1241. doi: 10.1186/s12885-021-08898-y.
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.
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.
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.
Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.
癌症干细胞（CSC）被认为与癌症的发生、进展和复发有关。已经描述了几种用于胰腺导管腺癌（PDAC）CSC 的生物标志物；然而，它们的功能和机制仍不清楚。
在这项研究中，对胰腺 CSC 富集球体和对照贴壁细胞进行了分泌组分析，以发现生物标志物。谷氧还蛋白 3（GLRX3）是一种在球体中上调的新候选物，用于评估其功能和临床意义。
PDAC CSC 群体、细胞系、患者组织和血液样本均表现出 GLRX3 的过表达。相比之下，GLRX3 沉默降低了细胞的体外增殖、迁移、集落形成和球体形成能力。GLRX3 敲低也减少了体内肿瘤的形成和生长。发现 GLRX3 调节 Met/PI3K/AKT 信号和干性相关分子。ELISA 结果表明，与健康对照组相比，PDAC 患者血清中的 GLRX3 表达升高。GLRX3 用于 PDAC 诊断的敏感性和特异性分别为 80.0%和 100%。当将 GLRX3 和 CA19-9 结合使用时，与单独使用 GLRX3 或 CA19-9 相比，敏感性显著提高至 98.3%。GLRX3 的高表达与接受根治性手术的患者无病生存不良相关。
总体而言，这些结果表明 GLRX3 是一种新型的诊断标志物和治疗靶点，可用于针对 CSC 的 PDAC。
