Czerwinska Patrycja, Jaworska Anna Maria, Wlodarczyk Nikola Agata, Mackiewicz Andrzej Adam
Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, 15 Garbary St., 61-866 Poznan, Poland.
Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary St., 61-866 Poznan, Poland.
Cancers (Basel). 2020 Oct 15;12(10):2998. doi: 10.3390/cancers12102998.
TRIM28 emerged as a guard of the intrinsic "state of cell differentiation", facilitating self-renewal of pluripotent stem cells. Recent reports imply TRIM28 engagement in cancer stem cell (CSC) maintenance, although the exact mechanism remains unresolved. high expression is associated with worse melanoma patient outcomes. Here, we investigated the association between level and melanoma stemness, and aligned it with the antitumor immune response to find the mechanism of "stemness high/immune low" melanoma phenotype acquisition. Based on the SKCM TCGA data, the expression profile, clinicopathological features, expression of correlated genes, and the level of stemness and immune scores were analyzed in patient samples. The biological function for differentially expressed genes was annotated with GSEA. Results were validated with additional datasets from R2: Genomics Analysis and Visualization Platform and in vitro with a panel of seven melanoma cell lines. All statistical analyses were accomplished using GraphPad Prism 8. TRIM28-expressing melanoma patients are characterized by worse outcomes and significantly different gene expression profiles than the TRIM28 cohort. high level related to higher melanoma stemness as measured with several distinct scores and TRIM28-expressing melanoma cell lines possess the greater potential of melanosphere formation. Moreover, TRIM28 melanoma tumors were significantly depleted with infiltrating immune cells, especially cytotoxic T cells, helper T cells, and B cells. Furthermore, emerged as a good predictor of "stemness high/immune low" melanoma phenotype. Our data indicate that TRIM28 might facilitate this phenotype by direct repression of interferon signaling. TRIM28 emerged as a direct link between stem cell-like phenotype and attenuated antitumor immune response in melanoma, although further studies are needed to evaluate the direct mechanism of TRIM28-mediated stem-like phenotype acquisition.
TRIM28作为内在“细胞分化状态”的守护者出现，促进多能干细胞的自我更新。最近的报告暗示TRIM28参与癌症干细胞（CSC）的维持，尽管确切机制仍未解决。高表达与黑色素瘤患者较差的预后相关。在这里，我们研究了TRIM28水平与黑色素瘤干性之间的关联，并将其与抗肿瘤免疫反应相结合，以寻找“干性高/免疫低”黑色素瘤表型获得的机制。基于SKCM TCGA数据，分析了患者样本中的TRIM28表达谱、临床病理特征、相关基因表达以及干性和免疫评分水平。用GSEA对差异表达基因的生物学功能进行注释。结果用来自R2：基因组学分析和可视化平台的其他数据集以及一组七种黑色素瘤细胞系进行体外验证。所有统计分析均使用GraphPad Prism 8完成。与TRIM28队列相比，表达TRIM28的黑色素瘤患者的特征是预后较差且基因表达谱明显不同。高水平与用几种不同评分测量的更高黑色素瘤干性相关，并且表达TRIM28的黑色素瘤细胞系具有更大的黑素球形成潜力。此外，TRIM28黑色素瘤肿瘤中浸润的免疫细胞，特别是细胞毒性T细胞、辅助性T细胞和B细胞明显减少。此外，TRIM28成为“干性高/免疫低”黑色素瘤表型的良好预测指标。我们的数据表明，TRIM28可能通过直接抑制干扰素信号传导来促进这种表型。TRIM28成为黑色素瘤中干细胞样表型与减弱的抗肿瘤免疫反应之间的直接联系，尽管需要进一步研究来评估TRIM28介导的干细胞样表型获得的直接机制。
