A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy

IF 4.8 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Neoplasia Pub Date : 2024-02-09 DOI:10.1016/j.neo.2024.100975
Casper W.F. van Eijck , Sergio Sabroso-Lasa , Gaby J. Strijk , Dana A.M. Mustafa , Amine Fellah , Bas Groot Koerkamp , Núria Malats , Casper H.J. van Eijck
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Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is often treated with FOLFIRINOX, a chemotherapy associated with high toxicity rates and variable efficacy. Therefore, it is crucial to identify patients at risk of early progression during treatment. This study aims to explore the potential of a multi-omics biomarker for predicting early PDAC progression by employing an in-depth mathematical modeling approach.

Methods

Blood samples were collected from 58 PDAC patients undergoing FOLFIRINOX before and after the first cycle. These samples underwent gene (GEP) and inflammatory protein expression profiling (IPEP). We explored the predictive potential of exclusively IPEP through Stepwise (Backward) Multivariate Logistic Regression modeling. Additionally, we integrated GEP and IPEP using Bayesian Kernel Regression modeling, aiming to enhance predictive performance. Ultimately, the FOLFIRINOX IPEP (FFX-IPEP) signature was developed.

Results

Our findings revealed that proteins exhibited superior predictive accuracy than genes. Consequently, the FFX-IPEP signature consisted of six proteins: AMN, BANK1, IL1RL2, ITGB6, MYO9B, and PRSS8. The signature effectively identified patients transitioning from disease control to progression early during FOLFIRINOX, achieving remarkable predictive accuracy with an AUC of 0.89 in an independent test set. Importantly, the FFX-IPEP signature outperformed the conventional CA19-9 tumor marker.

Conclusions

Our six-protein FFX-IPEP signature holds solid potential as a liquid biomarker for the early prediction of PDAC progression during toxic FOLFIRINOX chemotherapy. Further validation in an external cohort is crucial to confirm the utility of the FFX-IPEP signature. Future studies should expand to predict progression under different chemotherapies to enhance the guidance of personalized treatment selection in PDAC.

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炎症蛋白液体生物标记特征能准确预测 FOLFIRINOX 化疗期间早期胰腺癌的进展。
背景:胰腺导管腺癌(PDAC)通常采用 FOLFIRINOX 治疗,这种化疗方法毒性大、疗效不稳定。因此,在治疗过程中识别有早期进展风险的患者至关重要。本研究旨在通过采用深入的数学建模方法,探索多组学生物标志物预测PDAC早期进展的潜力:方法:58 名接受 FOLFIRINOX 治疗的 PDAC 患者在第一周期前后采集了血样。这些样本进行了基因(GEP)和炎性蛋白表达谱分析(IPEP)。我们通过逐步(后向)多元 Logistic 回归建模探索了 IPEP 专有的预测潜力。此外,我们还利用贝叶斯核回归模型整合了 GEP 和 IPEP,旨在提高预测性能。最终,我们开发出了 FOLFIRINOX IPEP(FFX-IPEP)特征:结果:我们的研究结果表明,蛋白质的预测准确性优于基因。因此,FFX-IPEP 标志由六种蛋白质组成:AMN、BANK1、IL1RL2、ITGB6、MYO9B 和 PRSS8。该特征能有效识别 FOLFIRINOX 期间从疾病控制向进展早期过渡的患者,在独立测试集中的 AUC 为 0.89,具有显著的预测准确性。重要的是,FFX-IPEP 特征优于传统的 CA19-9 肿瘤标志物:结论:我们的六蛋白 FFX-IPEP 特征作为一种液体生物标记物,在 FOLFIRINOX 毒性化疗期间早期预测 PDAC 病变进展方面具有坚实的潜力。为了证实FFX-IPEP特征的实用性,在外部队列中进行进一步验证至关重要。未来的研究应扩展到预测不同化疗的进展,以加强对 PDAC 个性化治疗选择的指导。
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来源期刊
Neoplasia
Neoplasia 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
82
审稿时长
26 days
期刊介绍: Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.
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