鉴定新型血浆蛋白作为有前景的非侵入性生物标志物用于胰腺导管腺癌的早期诊断和监测。

Identification of novel plasma proteins as promising noninvasive biomarker for early diagnosis and surveillance of pancreatic ductal adenocarcinoma.

作者信息

Liu Shuang, Su Jiachun, Zhao Hongzhe, Bai Ruihong, Zeng Lingxing, Xue Chunling, Deng Shuang, Liu Shaoqiu, Chen Ziming, Xu Zilan, Zhou Yifan, Zhao Sihan, Wu Xiaoyu, Peng Xinyi, Zhang Jialiang, Huang Xudong, Zheng Jian, Zhao Chongyu, Zheng Lu

机构信息

State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

出版信息

J Gastroenterol. 2025 Apr 26. doi: 10.1007/s00535-025-02252-w.

DOI:10.1007/s00535-025-02252-w

PMID:40285860

Abstract

BACKGROUND

Although cancer antigen 19-9 (CA 19-9) is the only FDA-approved biomarker for pancreatic ductal adenocarcinoma (PDAC), its diagnostic effectiveness is limited, as it may not be elevated in 15-25% of patients. This study aims to explore novel plasma proteins associated with PDAC as potential biomarkers for early diagnosis and clinical surveillance.

METHODS

Novel plasma protein biomarkers potentially causally associated with PDAC were identified using Mendelian randomization (MR). These biomarkers were validated in a multicenter study encompassing 230 tissue and 1,011 plasma samples to establish a diagnostic model for PDAC. Furthermore, their pre- and post-operative levels were compared to evaluate their potential as clinical surveillance biomarkers.

RESULTS

Genetically predicted expression of seven proteins potentially causally associated with an increased risk of PDAC. In a multicenter, large-scale study, Keratin 5 (KRT5) and Versican (VCAN) were identified as promising biomarkers for PDAC, with an area under the curve (AUC) of 0.90, and a combined panel including CA 19-9 achieved an AUC of 0.95. Additionally, plasma KRT5 and VCAN demonstrated superior diagnostic performance for early-stage PDAC with CA 19-9 levels below 37 U/mL (Stage I, AUC 0.85; Stage II, AUC 0.85). The specificity of plasma KRT5 and VCAN for PDAC was further validated by comparing their expression levels across various digestive cancers. Moreover, a significant decrease in plasma KRT5 and VCAN levels was observed post-surgery (P < 0.05), supporting their potential as biomarkers for clinical surveillance of PDAC.

CONCLUSIONS

Plasma KRT5 and VCAN proteins may serve as promising valuable biomarkers for the early diagnosis and clinical surveillance of PDAC.

摘要

背景

尽管癌抗原19-9（CA 19-9）是美国食品药品监督管理局（FDA）批准的唯一用于胰腺导管腺癌（PDAC）的生物标志物，但其诊断有效性有限，因为15%-25%的患者其水平可能并未升高。本研究旨在探索与PDAC相关的新型血浆蛋白，作为早期诊断和临床监测的潜在生物标志物。

方法

使用孟德尔随机化（MR）确定可能与PDAC有因果关系的新型血浆蛋白生物标志物。这些生物标志物在一项多中心研究中得到验证，该研究涵盖230份组织样本和1011份血浆样本，以建立PDAC的诊断模型。此外，比较了它们术前和术后的水平，以评估其作为临床监测生物标志物的潜力。

结果

七种蛋白的基因预测表达可能与PDAC风险增加有因果关系。在一项多中心大规模研究中，角蛋白5（KRT5）和多功能蛋白聚糖（VCAN）被确定为有前景的PDAC生物标志物，曲线下面积（AUC）为0.90，包括CA 19-9的联合检测组AUC达到0.95。此外，对于CA 19-9水平低于37 U/mL的早期PDAC，血浆KRT5和VCAN表现出卓越的诊断性能（I期，AUC 0.85；II期，AUC 0.85）。通过比较它们在各种消化系统癌症中的表达水平，进一步验证了血浆KRT5和VCAN对PDAC的特异性。此外，术后血浆KRT5和VCAN水平显著下降（P<0.05），支持它们作为PDAC临床监测生物标志物的潜力。