研究动态
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α3整合素的异常糖基化作为上皮性卵巢癌的诊断标志物。

Aberrant glycosylation of α3 integrins as diagnostic markers in epithelial ovarian cancer.

发表日期:2023 Mar 30
作者: Shruti Jain, Priyadharshini Parimelazhagan Santhi, Rufus Vinod, Shamima Afrin Ruma, Kaisa Huhtinen, Kim Pettersson, Karin Sundfeldt, Janne Leivo, Kamlesh Gidwani
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

糖基连接蛋白(ITG)和四跨膜蛋白CD63的稳定性和功能以及它们的相应相互作用伙伴与肿瘤生成过程中的异常有强烈关联。糖基化变化是癌细胞的普遍现象。本研究利用四跨膜蛋白和整合素分子探讨上皮性卵巢癌(EOC)中的糖基化变化。从10个EOC和5个良性卵巢囊肿液中固定了ITG和CD63,并用3种糖类结合蛋白(STn、WGA、UEA)与铕纳米粒子结合后进行追踪。还进行了总蛋白质测量(ITG和CD63免疫测定)。然后在77个卵巢囊肿液的整个队列中,对最有前途的糖基变异候选者进行了临床评估。此外,还在肝硬化(n=2)和EOC(n=4)的腹水样本中进行了其他测试。ITGα3(ITGα3STn)和CD63(CD63STn)的唾液酸化Tn抗体基础糖基变异物表现比相应的蛋白表位免疫分析(ITGα3IA和CD63IA)更好。联合ITGα3基础测定(ITGα3IA + ITGα3STn)检测了55个恶性和界限性病例中的49个,未检测到22个良性和健康的囊肿。我们的发现表明ITGα3STn的潜在诊断应用,结合总ITGα3IA,可以帮助减少不必要的手术。结果鼓励进一步研究这些新型测定方法在早期临床阶段检测EOC的潜在用途。版权所有©2023作者。由Elsevier B.V.出版。保留所有权利。
Glycans are strongly involved in stability and function of integrins (ITG) and tetraspanin protein CD63 and their respective interaction partners as they are dysregulated in the tumorigenic processes. Glycosylation changes is a universal phenomenon of cancer cells. In this study, glycosylation changes in epithelial ovarian cancer (EOC) are explored using tetraspanin and integrin molecules.ITG and CD63 were immobilized from 10 EOC and 5 benign ovarian cyst fluid on microtiter wells and traced with 3 glycan binding proteins (STn, WGA, UEA) conjugated on europium nanoparticles. Total protein measurements (ITG & CD63 immunoassays) were also performed. The most promising glycovariant candidates identified were then clinically evaluated on the whole cohort of 77 ovarian cyst fluids. Additional testing was performed in ascites fluid samples of liver cirrhosis (n=2) and EOC (n=4).Sialylated Tn antibody based glycovariants of ITGα3 (ITGα3STn) and CD63 (CD63STn) performed better than corresponding protein epitope-based immunoassays, ITGα3IA and CD63IA respectively. Combined ITGα3 based assays (ITGα3IA + ITGα3STn) detected 49 out of 55 malignant & borderline cases without detecting any of the 22 benign and healthy cysts.Our findings indicate the potential diagnostic application of ITGα3STn along with total ITGα3IA, which could help reduce the unnecessary surgeries. The results encourage studying further the potential use of these novel assays to detect EOC at earlier clinical stages.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.