A rigorous multi-laboratory study of known PDAC biomarkers identifies increased sensitivity and specificity over CA19-9 alone

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2024-09-12 DOI:10.1016/j.canlet.2024.217245

Brian Haab , Lu Qian , Ben Staal , Maneesh Jain , Johannes Fahrmann , Christine Worthington , Denise Prosser , Liudmila Velokokhatnaya , Camden Lopez , Runlong Tang , Mark W. Hurd , Gopalakrishnan Natarajan , Sushil Kumar , Lynette Smith , Sam Hanash , Surinder K. Batra , Anirban Maitra , Anna Lokshin , Ying Huang , Randall E. Brand

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引用次数: 0

Abstract

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p < 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p < 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial.

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对已知 PDAC 生物标志物进行的一项严格的多实验室研究发现，其灵敏度和特异性均高于单独使用 CA19-9 时的灵敏度和特异性

目前迫切需要一种能监测早期胰腺导管腺癌（PDAC）的血液检验。独立实验室报告的 PDAC 生物标志物可比单独使用 CA19-9 提高生物标志物的性能，但之前报告的生物标志物联合使用的性能尚不清楚。因此，我们使用来自 PDAC 患者和非 PDAC 对照受试者的共同盲法训练和验证样本集（分别为 132 份和 295 份血浆样本），在多个实验室之间开展了一项病例/对照研究，这些样本代表了监测发生的条件。我们分析了训练集，利用各实验室的生物标记物确定了候选生物标记物组合面板，并将固定面板应用于验证集。在训练集中确定的面板（CA19-9 与 CA199.STRA、LRG1、TIMP-1、TGM2、THSP2、ANG 和 MUC16.STRA）在验证集中取得了一致的性能。CA19-9与糖类生物标记物CA199.STRA的组合将灵敏度从CA19-9单独检测的0.44（特异性为0.98）提高到0.71（特异性为0.98）（p < 0.001，1000倍自引导）。同样，CA19-9 与蛋白质生物标记物 LRG1 和 CA199.STRA 的结合也将特异性从 CA19-9 的 0.16（灵敏度为 0.94）提高到 0.65（灵敏度为 0.89）（p < 0.001，1000 倍引导）。我们使用不包括 CA19-9 的生物标记物面板进一步验证了明显改善的性能。这项研究证实了对以前发现的生物标记物进行协调研究的有效性，并确定了这些生物标记物的面板，它们在严格的验证试验中显著提高了早期 PDAC 检测的灵敏度和特异性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.