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采用原位邻近连接分析检测黏液性卵巢癌组织中 MUC5AC 的血型抗原。

Analysis of blood group antigens on MUC5AC in mucinous ovarian cancer tissues using in situ proximity ligation assay.

机构信息

Department of Clinical Pathology, Sahlgrenska University Hostpital Gotenburg, 41345, Sweden.

Department of Medical Biochemistry, Sahlgrenska Academy, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden.

出版信息

Glycobiology. 2021 Dec 18;31(11):1464-1471. doi: 10.1093/glycob/cwab090.

DOI:10.1093/glycob/cwab090
PMID:34459484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8684467/
Abstract

MUC5AC has been indicated to be a marker for mucinous ovarian cancer (OC). We investigated the use of in situ proximity ligation assay (PLA) for blood group ABH expressing MUC5AC to differentiate between serous and mucinous OC, to validate preceding observations that also MUC5AC ABH expression is increased in mucinous OC. We developed PLA for anti-A, B, and H/anti-MUC5AC and a PLA using a combined lectin Ulex europaeus agglutinin I (UEA I)/anti-MUC5AC assay. The PLAs were verified with mass spectrometry, where mucinous OC secretor positive patients' cysts fluids containing ABH O-linked oligosaccharides also showed positive OC tissue PLA staining. A nonsecretor mucinous OC cyst fluid was negative for ABH and displayed negative PLA staining of the matched tissue. Using the UEA I/MUC5AC PLA, we screened a tissue micro array of 410 ovarian tissue samples from patients with various stages of mucinous or serous OC, 32 samples with metastasis to the ovaries and 34 controls. The PLA allowed differentiating mucinous tumors with a sensitivity of 84% and a specificity of 97% both against serous cancer but also compared to tissues from controls. This sensitivity is close to the expected incidence of secretor individuals in a population. The recorded sensitivity was also found to be higher compared to mucinous type cancer with metastasis to the ovaries, where only 32% were positive. We conclude that UEA 1/MUC5AC PLA allows glycospecific differentiation between serous and mucinous OC in patients with positive secretor status and will not identify secretor negative individuals with mucinous OC.

摘要

MUC5AC 已被证明是黏液性卵巢癌 (OC) 的标志物。我们研究了使用原位邻近连接分析 (PLA) 检测 ABH 血型表达的 MUC5AC，以区分浆液性和黏液性 OC，验证先前的观察结果，即黏液性 OC 中 MUC5AC ABH 表达也增加。我们开发了针对 A、B 和 H/抗-MUC5AC 的 PLA，以及使用混合凝集素欧洲菘蓝凝集素 I (UEA I)/抗-MUC5AC 检测法的 PLA。通过质谱验证了 PLA，其中黏液性 OC 分泌阳性患者的囊肿液含有 ABH O-连接寡糖，也显示 OC 组织 PLA 染色阳性。非分泌性黏液性 OC 囊肿液对 ABH 呈阴性，与匹配组织的 PLA 染色呈阴性。使用 UEA I/MUC5AC PLA，我们筛选了来自不同阶段黏液性或浆液性 OC 患者的 410 个卵巢组织样本的组织微阵列，包括 32 个转移到卵巢的样本和 34 个对照。PLA 允许区分黏液性肿瘤，其对浆液性癌症的敏感性为 84%，特异性为 97%，但也与对照组织相比。这种敏感性接近人群中分泌个体的预期发生率。与转移到卵巢的黏液性类型癌症相比，记录的敏感性也更高，其中只有 32% 为阳性。我们得出结论，UEA 1/MUC5AC PLA 允许在具有阳性分泌状态的患者中对浆液性和黏液性 OC 进行糖特异性区分，并且不会识别出具有黏液性 OC 的非分泌个体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/a44b73a25fd4/cwab090f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/09050b8381fd/cwab090f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/24d6a7f6cade/cwab090f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/22dba0a85313/cwab090f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/a44b73a25fd4/cwab090f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/09050b8381fd/cwab090f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/24d6a7f6cade/cwab090f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/22dba0a85313/cwab090f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b410/8684467/a44b73a25fd4/cwab090f4.jpg

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