Elucidating the mechanistic role of ovarian cancer biomarkers: Lessons learnt from affinity-proteomics

IF 5.5 2区 医学 Q1 HEMATOLOGY
Anna Mary Steitz , Silke Reinartz , Vanessa M. Beutgen , Rolf Müller , Elke Pogge von Strandmann , María Gómez-Serrano
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Abstract

A salient feature of ovarian carcinoma (OC) is its unique tumor microenvironment (TME) enabling early onset of transcoelomic dissemination via the malignant ascites, with the omentum as a preferred site of tumor metastasis. These traits together with typical late diagnosis and high incidence of chemoresistance render OC the most lethal gynecological malignancy. Deciphering the mechanisms allowing tumor progression and metastasis represents an important aim in OC research. Also, there is a high medical need to identify biomarkers that could serve as diagnostic tools for detection of early and recurrent disease. Due to the easy access, one overarching goal is to define clinically relevant blood biomarkers reflecting the pro-tumorigenic features of the TME. For its part, the ascites better reflects the tumor secretome by holding large amounts of stromal, immune and tumor cells, as well as soluble secreted factors and extracellular vesicles, which justifies a more detailed analysis of the ascites proteome. Despite previous efforts based on mass-spectrometry analyses, biomarkers derived from these studies have so far not been integrated into clinical practice. Novel approaches applying affinity-based proteomics have more recently revolutionized biomarker research by providing systematic high-throughput analysis and highly sensitive detection. In the following, we discuss key findings in OC research applying these approaches to unravel intercellular crosstalk within the TME while identifying novel biomarkers. Understanding the origin, function and clinical impact of putative biomarkers is crucial, not only to depict the intercellular communication in the OC TME, but also to develop targeted therapies and improved diagnostic tools.
阐明卵巢癌生物标志物的机制作用:亲和蛋白质组学的经验教训。
卵巢癌(OC)的一个显著特征是其独特的肿瘤微环境(TME),使其能够通过恶性腹水早期发生经体腔传播,而大网膜是肿瘤转移的首选部位。这些特点加上典型的晚期诊断和高发的化疗耐药,使卵巢癌成为最致命的妇科恶性肿瘤。揭示肿瘤进展和转移的机制是卵巢癌研究的一个重要目标。此外,鉴定生物标志物作为检测早期和复发性疾病的诊断工具也有很高的医学需求。由于易于获取,一个首要目标是定义临床相关的血液生物标志物,反映TME的致瘤性特征。腹水中含有大量的基质细胞、免疫细胞和肿瘤细胞,以及可溶性分泌因子和细胞外囊泡,能更好地反映肿瘤的分泌组,这就证明了对腹水蛋白质组进行更详细的分析是合理的。尽管以前的努力是基于质谱分析,但迄今为止,从这些研究中获得的生物标志物尚未整合到临床实践中。最近,应用基于亲和的蛋白质组学的新方法通过提供系统的高通量分析和高灵敏度检测,彻底改变了生物标志物的研究。在下文中,我们将讨论OC研究中的关键发现,应用这些方法来揭示TME内的细胞间串扰,同时识别新的生物标志物。了解假定的生物标志物的起源、功能和临床影响至关重要,不仅可以描述OC TME中的细胞间通讯,还可以开发靶向治疗和改进诊断工具。
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
CiteScore
11.00
自引率
3.20%
发文量
213
审稿时长
55 days
期刊介绍: Critical Reviews in Oncology/Hematology publishes scholarly, critical reviews in all fields of oncology and hematology written by experts from around the world. Critical Reviews in Oncology/Hematology is the Official Journal of the European School of Oncology (ESO) and the International Society of Liquid Biopsy.
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