Sluiter Nina, de Cuba Erienne, Kwakman Riom, Kazemier Geert, Meijer Gerrit, Te Velde Elisabeth Atie
Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Clin Exp Metastasis. 2016 Jun;33(5):401-16. doi: 10.1007/s10585-016-9791-0. Epub 2016 Apr 13.
Peritoneal dissemination is diagnosed in 10-25 % of colorectal cancer patients. Selected patients are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. For these patients, earlier diagnosis, optimised selection criteria and a personalised approach are warranted. Biomarkers could play a crucial role here. However, little is known about possible candidates. Considering tumour cell adhesion as a key step in peritoneal dissemination, we aim to provide an overview of the functional importance of adhesion molecules in peritoneal dissemination and discuss the prognostic, diagnostic and therapeutic options of these candidate biomarkers. A systematic literature search was conducted according to the PRISMA guidelines. In 132 in vitro, ex vivo and in vivo studies published between 1995 and 2013, we identified twelve possibly relevant adhesion molecules in various cancers that disseminate peritoneally. The most studied molecules in tumour cell adhesion are integrin α2β1, CD44 s and MUC16. Furthermore, L1CAM, EpCAM, MUC1, sLe(x) and Le(x), chemokine receptors, Betaig-H3 and uPAR might be of clinical importance. ICAM1 was found to be less relevant in tumour cell adhesion in the context of peritoneal metastases. Based on currently available data, sLe(a) and MUC16 are the most promising prognostic biomarkers for colorectal peritoneal metastases that may help improve patient selection. Different adhesion molecules appear expressed in haematogenous and transcoelomic spread, indicating two different attachment processes. However, our extensive assessment of available literature reveals that knowledge on metastasis-specific genes and their possible candidates is far from complete.
10%-25%的结直肠癌患者被诊断为腹膜播散。部分患者接受了减瘤手术和腹腔内热灌注化疗。对于这些患者，有必要进行更早的诊断、优化选择标准并采取个性化治疗方法。生物标志物在此可能发挥关键作用。然而，对于可能的候选标志物却知之甚少。考虑到肿瘤细胞黏附是腹膜播散的关键步骤，我们旨在概述黏附分子在腹膜播散中的功能重要性，并讨论这些候选生物标志物的预后、诊断和治疗选择。根据PRISMA指南进行了系统的文献检索。在1995年至2013年间发表的132项体外、离体和体内研究中，我们在各种腹膜播散性癌症中鉴定出12种可能相关的黏附分子。在肿瘤细胞黏附中研究最多的分子是整合素α2β1、CD44s和MUC16。此外，L1CAM、EpCAM、MUC1、sLe(x)和Le(x)、趋化因子受体、Betaig-H3和uPAR可能具有临床重要性。在腹膜转移的背景下，发现ICAM1与肿瘤细胞黏附的相关性较小。基于目前可用的数据，sLe(a)和MUC16是结直肠癌腹膜转移最有前景的预后生物标志物，可能有助于改善患者的选择。不同的黏附分子似乎在血行转移和经体腔转移中表达不同，表明存在两种不同的附着过程。然而,我们对现有文献的广泛评估表明，关于转移特异性基因及其可能的候选基因的知识还远远不够完善。
