Gholiha Alex Reza, Hollander Peter, Löf Liza, Larsson Anders, Hashemi Jamileh, Ulfstedt Johan Mattsson, Molin Daniel, Amini Rose-Marie, Freyhult Eva, Kamali-Moghaddam Masood, Enblad Gunilla
Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, SE-752 36 Uppsala, Sweden.
Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, SE-752 36 Uppsala, Sweden.
Cancers (Basel). 2021 Dec 21;14(1):9. doi: 10.3390/cancers14010009.
In classical Hodgkin Lymphoma (cHL), immunoediting via protein signaling is key to evading tumor surveillance. We aimed to identify immune-related proteins that distinguish diagnostic cHL tissues (=diagnostic tumor lysates, = 27) from control tissues (reactive lymph node lysates, = 30). Further, we correlated our findings with the proteome plasma profile between cHL patients ( = 26) and healthy controls ( = 27). We used the proximity extension assay (PEA) with the OlinkTM multiplex Immuno-Oncology panel, consisting of 92 proteins. Univariate, multivariate-adjusted analysis and Benjamini-Hochberg's false discovery testing (=Padj) were performed to detect significant discrepancies. Proteins distinguishing cHL cases from controls were more numerous in plasma (30 proteins) than tissue (17 proteins), all Padj < 0.05. Eight of the identified proteins in cHL tissue (PD-L1, IL-6, CCL17, CCL3, IL-13, MMP12, TNFRS4, and LAG3) were elevated in both cHL tissues and cHL plasma compared with control samples. Six proteins distinguishing cHL tissues from controls tissues were significantly correlated to PD-L1 expression in cHL tissue (IL-6, MCP-2, CCL3, CCL4, GZMB, and IFN-gamma, all ≤0.05). In conclusion, this study introduces a distinguishing proteomic profile in cHL tissue and potential immune-related markers of pathophysiological relevance.
在经典型霍奇金淋巴瘤(cHL)中,通过蛋白质信号传导进行免疫编辑是逃避肿瘤监测的关键。我们旨在鉴定能够区分诊断性cHL组织(=诊断性肿瘤裂解物,n = 27)与对照组织(反应性淋巴结裂解物,n = 30)的免疫相关蛋白。此外,我们将研究结果与cHL患者(n = 26)和健康对照(n = 27)之间的血浆蛋白质组图谱进行了关联分析。我们使用了OlinkTM多重免疫肿瘤学检测板的邻近延伸分析(PEA),该检测板包含92种蛋白质。进行单变量、多变量调整分析以及Benjamini-Hochberg错误发现率检验(=Padj)以检测显著差异。区分cHL病例与对照的蛋白质在血浆中(30种蛋白质)比在组织中(17种蛋白质)更多,所有Padj < 0.05。与对照样本相比,在cHL组织中鉴定出的8种蛋白质(PD-L1、IL-6、CCL17、CCL3、IL-13、MMP12、TNFRS4和LAG3)在cHL组织和cHL血浆中均升高。区分cHL组织与对照组织的6种蛋白质与cHL组织中PD-L1的表达显著相关(IL-6、MCP-2、CCL3、CCL4、GZMB和IFN-γ,所有P≤0.05)。总之,本研究介绍了cHL组织中独特的蛋白质组图谱以及具有病理生理相关性的潜在免疫相关标志物。