Resident Physician, Department of Dermatology, Johns Hopkins University , Baltimore , MD , USA.
PhD student in Biostatistics and Epidemiology, Bloomberg School of Public Health, Johns Hopkins University , Baltimore , MD , USA.
Platelets. 2019;30(8):1042-1046. doi: 10.1080/09537104.2019.1572879. Epub 2019 Feb 13.
Cancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality. Using multivariable analysis, patients with thrombocytosis around time of diagnosis were more likely to present with distant metastasis (Prevalence Ratio 3.5, 95% CI 2.35-5.22). In patients with metastatic disease and in all stages combined, thrombocytosis predicted decreased 5-year overall survival in univariate and multivariable analysis, and this was most pronounced during the first year after diagnosis. Finally, we show that mice with thrombocytopenia due to the lack of heat shock protein gp96 in their megakaryocytes are protected from melanoma dissemination to the lungs. These findings are concordant with preclinical studies showing a role for platelets in cancer metastasis and suppression of antitumor immunity, further supporting targeting platelets as an adjuvant to immunotherapy in melanoma.
癌症是一种慢性炎症状态，常伴有血小板计数升高。癌细胞诱导巨核细胞生成并激活血小板，进而促进癌症的侵袭和转移。在这项研究中，我们调查了血小板计数与黑色素瘤分期和总生存期的相关性。这是一项回顾性队列研究，纳入了 2000 年至 2016 年期间在一家三级医疗中心诊断或治疗的 642 名黑色素瘤患者。多变量分析调整了年龄、性别、分期和治疗方式。多变量分析显示，诊断时血小板增多的患者更有可能出现远处转移（患病率比 3.5，95%置信区间 2.35-5.22）。在转移性疾病患者和所有分期患者中，血小板增多均预测无复发生存期缩短，在诊断后第一年最为明显。最后，我们发现由于巨核细胞缺乏热休克蛋白 gp96 而导致血小板减少的小鼠，其黑色素瘤向肺部的播散受到保护。这些发现与临床前研究一致，表明血小板在癌症转移和抑制抗肿瘤免疫中起作用，进一步支持将血小板作为黑色素瘤免疫治疗的辅助手段。
