Wijetunga Imeshi, McVeigh Laura E, Charalambous Antonia, Antanaviciute Agne, Carr Ian M, Nair Amit, Prasad K Raj, Ingram Nicola, Coletta P Louise
Leeds Institute of Medical Research, Wellcome Trust Brenner Building, St James's University Hospital, Leeds LS9 7TF, UK.
Department of Hepatobiliary and Transplant Surgery, St. James's University Hospital, Leeds LS9 7TF, UK.
Cancers (Basel). 2020 Sep 30;12(10):2817. doi: 10.3390/cancers12102817.
Cholangiocarcinoma (CCA) is a rare disease with poor outcomes and limited research efforts into novel treatment options. A systematic review of CCA biomarkers was undertaken to identify promising biomarkers that may be used for theranosis (therapy and diagnosis). MEDLINE/EMBASE databases (1996-2019) were systematically searched using two strategies to identify biomarker studies of CCA. The PANTHER Go-Slim classification system and STRING network version 11.0 were used to interrogate the identified biomarkers. The TArget Selection Criteria for Theranosis (TASC-T) score was used to rank identified proteins as potential targetable biomarkers for theranosis. The following proteins scored the highest, CA9, CLDN18, TNC, MMP9, and EGFR, and they were evaluated in detail. None of these biomarkers had high sensitivity or specificity for CCA but have potential for theranosis. This review is unique in that it describes the process of selecting suitable markers for theranosis, which is also applicable to other diseases. This has highlighted existing validated markers of CCA that can be used for active tumor targeting for the future development of targeted theranostic delivery systems. It also emphasizes the relevance of bioinformatics in aiding the search for validated biomarkers that could be repurposed for theranosis.
胆管癌（CCA）是一种罕见疾病，预后较差，针对新型治疗方案的研究力度有限。我们对CCA生物标志物进行了系统综述，以识别可能用于治疗诊断（治疗与诊断）的有前景的生物标志物。使用两种策略对MEDLINE/EMBASE数据库（1996 - 2019年）进行系统检索，以识别CCA的生物标志物研究。使用PANTHER精简版分类系统和STRING网络版本11.0对所识别的生物标志物进行分析。使用治疗诊断的目标选择标准（TASC - T）评分对所识别的蛋白质作为治疗诊断的潜在可靶向生物标志物进行排名。以下蛋白质得分最高：CA9、CLDN18、TNC、MMP9和EGFR，并对它们进行了详细评估。这些生物标志物对CCA均没有高敏感性或特异性，但具有治疗诊断的潜力。本综述的独特之处在于它描述了为治疗诊断选择合适标志物的过程，这也适用于其他疾病。这突出了CCA现有的经过验证的标志物，可用于未来靶向治疗诊断递送系统的活性肿瘤靶向。它还强调了生物信息学在辅助寻找可重新用于治疗诊断的经过验证的生物标志物方面的相关性。
