泛癌单细胞分析揭示皮肤肿瘤中癌症相关成纤维细胞的异质性

IF 3.8 4区 医学 Q2 GENETICS & HEREDITY
Yichi Zhang, Zhijie Zhao, Wenyi Huang, Byeong Seop Kim, Li Lin, Xin Li, Mengyuan Hou, Li Li, Yan Zhang, Wenjing Xi, Gang Chai
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引用次数: 0

摘要

背景:癌症相关成纤维细胞(CAFs)是一类异质性细胞,对肿瘤微环境(TME)的重塑至关重要。鉴于它们对肿瘤进展的重大影响,尤其是在皮肤癌中,深入了解它们的特征和功能至关重要:本研究采用单细胞转录组分析方法,探讨了基底细胞癌、黑色素瘤和头颈部鳞状细胞癌这三大类皮肤癌中 CAFs 的多样性。我们应用了基因本体(GO)、京都基因和基因组百科全书(KEGG)、基因组富集分析(GSEA)、伪时间追踪、代谢谱分析和干性评估等分析技术来划分和定义已确定的CAF亚群的功能属性:我们的分析在所研究的肿瘤类型中成功划分出九个不同的CAF亚群。特别值得关注的是,我们发现了一种新的 CAF 亚型,命名为 C0,是基底细胞癌的专属亚型。该亚型表现出与侵袭和破坏能力相关的表型特征,与基底细胞癌的进展密切相关。该亚群的确定为了解 CAFs 在癌症生物学中的作用提供了新的视角,并为靶向治疗策略开辟了途径:我们对 BCC、MA 和 HNSCC 这三种癌症进行了泛癌症分析,重点研究了 TME 中的肿瘤成纤维细胞。无监督聚类将CAF分为九个亚群,其中C0亚群与BCC-CAF有很强的对应性,并具有侵袭性-破坏性相关表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pan-Cancer Single-Cell Analysis Revealing the Heterogeneity of Cancer-Associated Fibroblasts in Skin Tumors.

Background: Cancer-Associated Fibroblasts (CAFs) constitute a heterogeneous group of cells critical for the remodeling of the tumor microenvironment (TME). Given their significant impact on tumor progression, particularly in skin cancers, a deeper understanding of their characteristics and functions is essential.

Methods: This study employed a single-cell transcriptomic analysis to explore the diversity of CAFs within three major types of skin cancer: basal cell carcinoma, melanoma, and head and neck squamous cell carcinoma. We applied analytical techniques, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), pseudotime tracking, metabolic profiling, and stemness assessment to delineate and define the functional attributes of identified CAF subgroups.

Results: Our analysis successfully delineated nine distinct CAF subgroups across the studied tumor types. Of particular interest, we identified a novel CAF subtype, designated as C0, exclusive to basal cell carcinoma. This subtype exhibits phenotypic traits associated with invasive and destructive capabilities, significantly correlating with the progression of basal cell carcinoma. The identification of this subgroup provides new insights into the role of CAFs in cancer biology and opens avenues for targeted therapeutic strategies.

Conclusion: A pan-cancer analysis was performed on three cancers, BCC, MA, and HNSCC, focusing on tumor fibroblasts in TME. Unsupervised clustering categorized CAF into nine subpopulations, among which the C0 subpopulation had a strong correspondence with BCC-CAF and an invasive- destructive-related phenotype.

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来源期刊
Current gene therapy
Current gene therapy 医学-遗传学
CiteScore
6.70
自引率
2.80%
发文量
46
期刊介绍: Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.
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