Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of Helsinki, Helsinki, Finland.
Cancer Sci. 2022 Jan;113(1):17-27. doi: 10.1111/cas.15199. Epub 2021 Nov 24.
Lymphangiogenesis is a key process in cancer development and metastasis. Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) is a widely used marker for lymphatic endothelial cells (LEC), which also mediates immune and cancer cell migration. Recently, LYVE-1-positive tumor cells were shown to acquire LEC-like phenotype and exploit this receptor for lymphatic dissemination. Furthermore, selective targeting of LYVE-1 impaired the growth of cancer-related vasculature and reduced metastasis in vivo, signifying its role in therapeutic and prognostic applications. Although numerous studies have investigated the role of LYVE-1 in cancer, a unifying detailed review of its prognostic utility is lacking to date. Thus, we compiled and critically appraised evidence from clinical studies comprising a total of 2352 patients diagnosed with different types of cancer and using a variety of experimental approaches. Collectively, most studies revealed a significant association between LYVE-1 overexpression and dismal outcome of at least one survival estimate. Furthermore, the importance of vasculature location, intra- or peritumoral, and the influence of various lymphangiogenesis-related parameters, such as lymphatic vessel density and invasion, were discussed. However, the specificity of LYVE-1 staining is challenged by its expression in non-LEC cells, implying the need for double labelling to better estimate its prognostic significance. In conclusion, this is to our knowledge the first comprehensive systematic review on the prognostic value of LYVE-1 in cancer. More well-designed studies across different populations and the development of standardized protocols would be paramount for the consistency of LYVE-1 findings and for its potential transferability to clinical practice in future.
淋巴管生成是癌症发展和转移的关键过程。淋巴管内皮透明质酸受体 1（LYVE-1）是淋巴管内皮细胞（LEC）的广泛使用标志物，它也介导免疫和癌细胞迁移。最近，LYVE-1 阳性肿瘤细胞被证明获得了 LEC 样表型，并利用该受体进行淋巴扩散。此外，选择性靶向 LYVE-1 可破坏与癌症相关的血管生长并减少体内转移，表明其在治疗和预后应用中的作用。尽管许多研究已经研究了 LYVE-1 在癌症中的作用，但迄今为止，缺乏对其预后效用的统一详细综述。因此，我们编译并批判性地评估了总共包含 2352 名不同类型癌症患者的临床研究证据，并使用了各种实验方法。总的来说，大多数研究表明，LYVE-1 过表达与至少一种生存估计的不良预后之间存在显著关联。此外，还讨论了血管位置、肿瘤内或肿瘤周围的重要性，以及各种淋巴管生成相关参数（如淋巴管密度和侵袭）的影响。然而，LYVE-1 染色的特异性受到其在非 LEC 细胞中表达的挑战，这意味着需要进行双重标记以更好地估计其预后意义。总之，这是我们所知的第一个关于 LYVE-1 在癌症中的预后价值的全面系统综述。在不同人群中进行更多设计良好的研究，并制定标准化方案对于 LYVE-1 发现的一致性以及其在未来向临床实践转移的潜在性至关重要。
