生物标志物从发现到临床应用:面对肺癌的硅学临床前验证方法。

IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Biomarker Insights Pub Date : 2024-10-03 eCollection Date: 2024-01-01 DOI:10.1177/11772719241287400
Medi Kori, Esra Gov, Kazim Yalcin Arga, Raghu Sinha
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引用次数: 0

摘要

背景:临床生物标志物可根据疾病风险、预后和/或对治疗的反应对患者进行更好的分类。尽管价格低廉的基于组学的方法为更快地确定推定生物标志物铺平了道路,但生物标志物的验证是将发现转化为临床应用的必要条件:因此,在本研究中,我们强调了硅学方法的潜力,并提出和应用了 3 个新颖的硅学临床前验证步骤,以更好地确定真正适合临床投资的生物标志物:由于蛋白质生物标记物与其他分子生物标记物在临床中的重要性日益增加,而肺癌是癌症相关死亡的最常见原因,因此我们以肺癌蛋白质生物标记物为例来应用我们的硅学临床前验证方法:我们收集了3个病例(肺腺癌-LUAD、鳞状细胞癌-LUSC和未指定肺癌)中报告的蛋白质生物标志物,并评估了这些蛋白质生物标志物是否具有改变癌症的特性(即作为肿瘤抑制因子或肿瘤蛋白,代表癌症标志物),是否在体液中表达,以及是否可以被FDA批准的药物靶向:我们收集了 3008 个肺癌蛋白质生物标记物、1189 个 LUAD 蛋白标记物和 182 个 LUSC 蛋白标记物。在这些肺癌、LUAD 和 LUSC 蛋白质生物标记物中,分别只有 28、25 和 6 个蛋白质生物标记物通过了 3 个硅学临床前验证步骤,其中分别只有 5 和 2 个生物标记物对肺癌和 LUAD 具有特异性:在这项研究中,我们采用了硅学临床前验证方法对肺癌病例的蛋白质生物标志物进行了验证。不过,这种方法也可应用于所有癌症生物标志物。我们相信,这种方法将极大地促进癌症生物标志物进入临床阶段,并为未来的生物标志物研究提供巨大的潜力。
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Biomarkers From Discovery to Clinical Application: In Silico Pre-Clinical Validation Approach in the Face of Lung Cancer.

Background: Clinical biomarkers, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker identification of putative biomarkers, validation of biomarkers is necessary for translation of discoveries into clinical application.

Objective: Accordingly, in this study, we emphasize the potential of in silico approaches and have proposed and applied 3 novel sequential in silico pre-clinical validation steps to better identify the biomarkers that are truly desirable for clinical investment.

Design: As protein biomarkers are becoming increasingly important in the clinic alongside other molecular biomarkers and lung cancer is the most common cause of cancer-related deaths, we used protein biomarkers for lung cancer as an illustrative example to apply our in silico pre-clinical validation approach.

Methods: We collected the reported protein biomarkers for 3 cases (lung adenocarcinoma-LUAD, squamous cell carcinoma-LUSC, and unspecified lung cancer) and evaluated whether the protein biomarkers have cancer altering properties (i.e., act as tumor suppressors or oncoproteins and represent cancer hallmarks), are expressed in body fluids, and can be targeted by FDA-approved drugs.

Results: We collected 3008 protein biomarkers for lung cancer, 1189 for LUAD, and 182 for LUSC. Of these protein biomarkers for lung cancer, LUAD, and LUSC, only 28, 25, and 6 protein biomarkers passed the 3 in silico pre-clinical validation steps examined, and of these, only 5 and 2 biomarkers were specific for lung cancer and LUAD, respectively.

Conclusion: In this study, we applied our in silico pre-clinical validation approach the protein biomarkers for lung cancer cases. However, this approach can be applied and adapted to all cancer biomarkers. We believe that this approach will greatly facilitate the transition of cancer biomarkers into the clinical phase and offers great potential for future biomarker research.

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来源期刊
Biomarker Insights
Biomarker Insights MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.00
自引率
0.00%
发文量
26
审稿时长
8 weeks
期刊介绍: An open access, peer reviewed electronic journal that covers all aspects of biomarker research and clinical applications.
期刊最新文献
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