研究概要
然而,约 1-2% 的 BCC 病例具有局部侵袭性,转移风险高,且常出现化疗耐药,称为晚期 BCC。
中文摘要
基底细胞癌(BCC)是最常见的皮肤癌,在西方国家约占新发癌症病例的三分之一。多数 BCC 属低危“常规”病灶,可手术切除或使用化疗药物治疗。然而,约 1%–2% 的 BCC 局部侵袭性强、转移风险高,且常产生化疗耐药,称为晚期 BCC。目前尚无可重现晚期 BCC、乃至中危和高危早期 BCC 的动物模型或细胞系。我们此前发现,侵袭性 BCC 肿瘤表现出 Th2 细胞因子炎症谱、间充质干细胞特性和巨噬细胞诱导的肿瘤炎症。本研究旨在实体器官恶性肿瘤中寻找可能的 BCC“近亲”,即肿瘤微环境中免疫细胞比例相似的肿瘤。研究者采用 CIBERSORTx 免疫细胞类型解卷积及 xCell 细胞类型富集分析,确定肿瘤微环境与 BCC 最相似的三种癌症。嫌色性肾细胞癌、肉瘤和皮肤黑色素瘤在多种细胞类型方面与 BCC 显著相似,特别是 CD4⁺ T 淋巴细胞、γδ T 淋巴细胞及 NK 细胞群。随后进一步查阅文献,研究 BCC 与其“近亲”的相似性及新型治疗靶点。通过识别与 BCC 最相似的癌症,研究者希望提出可药物靶向的通路,并为建立可靠的晚期 BCC 动物或细胞系模型提供依据。
展开英文摘要原文
Basal cell carcinoma (BCC) is the most common form of skin cancer, contributing to nearly a third of new cancer cases in Western countries. Most BCCs are considered low risk "routine" lesions that can either be excised through surgery or treated with chemotherapeutic agents. However, around 1-2% of BCC cases are locally aggressive, present a high risk of metastasis, and often develop chemoresistance, termed advanced BCC. There currently exists no animal model or cell line that can recapitulate advanced BCC, let alone intermediate-risk and high-risk early BCC. We previously found that aggressive BCC tumours presented a Th2 cytokine inflammation profile, mesenchymal stem cell properties, and macrophage-induced tumoral inflammation. In this study, we aimed to identify potential BCC "relatives" among solid-organ malignancies who present similar immune cell proportions in their microenvironment compositions. Using immune cell type deconvolution by CIBERSORTx, and cell type enrichment by xCell, we determined three cancers with the most similar tumour microenvironments as compared to BCC. Specifically, chromophobe renal cell carcinoma, sarcoma, and skin cutaneous melanoma presented significance in multiple cell types, namely in CD4+ T lymphocytes, gammadelta T lymphocytes, and NK cell populations. Consequently, further literature analysis was conducted to understand similarities between BCC and its "relatives", as well as investigating novel treatment targets. By identifying cancers most like BCC, we hope to propose prospective druggable pathways, as well as to gain insight on developing a reliable animal or cell line model to represent advanced BCC.
论文信息
- 作者
- Zhang ER、Ghezelbash S、Xie P、Fotovati M、Litvinov IV、Lefrançois P
- 单位
- Faculty of Medicine, McGill University, Montreal, QC H3T 1E2, Canada.Canada
- 期刊
- Cancers2023 Jan 2