Department of Respiratory Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Respiratory Medicine, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Brief Bioinform. 2020 Mar 23;21(2):709-718. doi: 10.1093/bib/bbz019.
MCAM (CD146) is a cell surface adhesion molecule that has been reported to promote cancer development, progression and metastasis and is considered as a potential tumor biomarker and therapeutic target. However, inconsistent reports exist, and its clinical value is yet to be confirmed. Here we took advantage of several large genomic data collections (Genotype-Tissue Expression, The Cancer Genome Atlas and Cancer Cell Line Encyclopedia) and comprehensively analyzed MCAM expression in thousands of normal and cancer samples and cell lines along with their clinical phenotypes and drug response information. Our results show that MCAM is very highly expressed in large vessel tissues while majority of tissues have low or minimal expression. Its expression is dramatically increased in a few tumors but significantly decreased in most other tumors relative to their pairing normal tissues. Increased MCAM expression is associated with a higher tumor stage and worse patient survival for some less common tumors but not for major ones. Higher MCAM expression in primary tumors may be complicated by tumor-associated or normal stromal blood vessels yet its significance may differ from the one from cancer cells. MCAM expression is weakly associated with the response to a few small molecular drugs and the association with targeted anti-BRAF agents suggests its involvement in that pathway which warrants further investigation.
MCAM(CD146)是一种细胞表面黏附分子,据报道它可促进癌症的发生、发展和转移,被认为是一种潜在的肿瘤标志物和治疗靶点。然而,目前存在不一致的报道,其临床价值尚待证实。在这里,我们利用了几个大型基因组数据集(Genotype-Tissue Expression、The Cancer Genome Atlas 和 Cancer Cell Line Encyclopedia),并对数千个正常和癌症样本以及细胞系及其临床表型和药物反应信息进行了综合分析。我们的结果表明,MCAM 在大血管组织中高度表达,而大多数组织的表达水平较低或微不足道。在一些肿瘤中,MCAM 的表达显著增加,但与配对的正常组织相比,大多数其他肿瘤的表达显著降低。MCAM 表达增加与一些罕见肿瘤的更高肿瘤分期和更差的患者生存率相关,但与主要肿瘤无关。原发性肿瘤中 MCAM 的高表达可能与肿瘤相关或正常基质血管有关,但它的意义可能与来自癌细胞的意义不同。MCAM 的表达与少数小分子药物的反应弱相关,与靶向抗 BRAF 药物的关联表明其参与了该途径,这需要进一步研究。