rBC2LCN 反应性 SERPINA3 是胰腺导管腺癌的候选糖生物标志物。

rBC2LCN-reactive SERPINA3 is a glycobiomarker candidate for pancreatic ductal adenocarcinoma.

机构信息

Cellular and Molecular Biotechnology Research Institute, Multicellular System Regulation Research Group, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.

Department of Surgery, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.

出版信息

Glycobiology. 2023 May 17;33(4):342-352. doi: 10.1093/glycob/cwad009.

DOI:10.1093/glycob/cwad009

PMID:36728830

Abstract

Early detection is urgently needed to improve the patient's pancreatic ductal adenocarcinoma (PDAC) survival. Previously, we identified a novel tumor-associated glycan, H-type3, which is expressed on PDAC cells and is detected by rBC2LCN (recombinant N-terminal domain of BC2L-C identified from Burkholderia cenocepacia) lectin. Here, we identified that SERPINA3 is an rBC2LCN-reactive glycoprotein (BC2-S3) secreted from PDAC cells into the blood in patients with PDAC by liquid chromatography-tandem mass spectrometry analysis and lectin blotting. In immune staining, BC2-S3 was detected specifically in the tumor but not in normal tissues of PDAC. Lectin-ELISA was then developed to measure the serum level of BC2-S3 in healthy control (HC, n = 99) and patients with PDAC (n = 88). BC2-S3 exhibited higher in patients with PDAC than in those with HC. BC2-S3 showed similar diagnostic performance in all stages of PDAC (stages IA-IV, true positive rate = 76.1%, true negative rate = 81.8%) to CA19-9 (72.7%, 75.8%). Remarkably, BC2-S3 showed a significantly higher detection rate (89.7%) for early stage PDAC (IA-IIA) than CA19-9 (62.1%, P = 0.029). The combination of BC2-S3 and CA19-9 further improved the diagnostic ability for all stages of PDAC (81.8%, 87.9%). In conclusion, BC2-S3 is a glycobiomarker candidate for PDAC.

摘要

早期检测对于改善胰腺导管腺癌（PDAC）患者的生存状况至关重要。此前，我们鉴定了一种新型肿瘤相关糖抗原 H 型 3（H-type3），它在 PDAC 细胞上表达，并可被 rBC2LCN（从伯克霍尔德氏菌属中鉴定的 BC2L-C 的 N 端结构域重组蛋白）凝集素所识别。在此，我们通过液相色谱-串联质谱分析和凝集素印迹法鉴定出 SERPINA3 是一种由 PDAC 细胞分泌到血液中的 rBC2LCN 反应性糖蛋白（BC2-S3）。免疫染色显示，BC2-S3 在 PDAC 的肿瘤组织中特异性表达，而在正常组织中不表达。随后开发了凝集素 ELISA 来测量健康对照者（HC，n=99）和 PDAC 患者（n=88）的血清 BC2-S3 水平。结果显示，BC2-S3 在 PDAC 患者中的表达水平高于 HC。BC2-S3 在 PDAC 的所有分期（IA-IV 期）的诊断性能与 CA19-9 相似（真阳性率=76.1%，真阴性率=81.8%）。值得注意的是，BC2-S3 对早期 PDAC（IA-IIA 期）的检测率（89.7%）明显高于 CA19-9（62.1%，P=0.029）。BC2-S3 与 CA19-9 的联合应用进一步提高了对所有分期 PDAC 的诊断能力（81.8%，87.9%）。综上所述，BC2-S3 是一种 PDAC 的候选糖生物标志物。