作为多维生物标记物的TCF3:泛癌分析中的致癌性、基因组改变和免疫景观

IF 3.3 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Huiling Nie, Yang Yu, Siqi Zhou, Yue Xu, Xi Chen, Xun Qin, Zhangyu Liu, Jiayu Huang, Hailiang Zhang, Jin Yao, Qin Jiang, Bingbing Wei, Xiaojian Qin
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引用次数: 0

摘要

转录因子 3(TCF3)是 TCF/LEF 家族的重要成员,在肿瘤发生过程中起着关键作用。然而,它对肿瘤微环境(TME)和癌症表型的影响仍然难以捉摸。我们对 TCF3 的表达、DNA 变异图谱、预后影响以及与 TME 和免疫学方面的关联进行了详尽的分析。这项研究基于一个大规模的泛癌症队列,包括来自多个独立数据集的 17,000 多名癌症患者,并通过体外检测进行了验证。我们的研究结果表明,在泛癌症分析中,正常组织和肿瘤组织的 TCF3/4/7 表达模式存在差异。TCF3在不同癌症类型中的突变分析显示,胆道癌的突变率最高。此外,TCF3/4/7 的突变和单核苷酸变异对患者的预后也有不同的影响。重要的是,在所有癌症组群和接受免疫检查点抑制剂治疗的患者中,TCF3是预测生存率的有力指标。TCF3表达的升高与侵袭性更强的癌症亚型相关,这一点已通过免疫组化和不同队列数据得到验证。此外,TCF3的表达与肿瘤内异质性和血管生成呈正相关。体外研究表明,TCF3 参与了上皮-间质转化、迁移、侵袭和血管生成。这些作用很可能是通过 TCF3 与 NF-κB/MMP2 通路的相互作用介导的,而在人类葡萄膜黑色素瘤 MUM2B 细胞中,IL-17A 可调节 NF-κB/MMP2 通路。这项研究首次阐明了TCF3与DNA变异图谱、预后结果以及多种癌症背景下的TME之间的重要关联。TCF3有望成为诊断的分子标记和新型治疗策略的潜在靶点,尤其是在葡萄膜黑色素瘤中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TCF3 as a multidimensional biomarker: oncogenicity, genomic alterations, and immune landscape in pan-cancer analysis.

Transcription factor 3 (TCF3), a pivotal member of the TCF/LEF family, plays a critical role in tumorigenesis. Nonetheless, its impact on the tumor microenvironment (TME) and cancer phenotypes remains elusive. We perform an exhaustive analysis of TCF3 expression, DNA variation profiles, prognostic implications, and associations with the TME and immunological aspects. This study is based on a large-scale pan-cancer cohort, encompassing over 17,000 cancer patients from multiple independent datasets, validated by in vitro assays. Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses. Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer. Additionally, mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis. Importantly, TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors. Elevated TCF3 expression is correlated with more aggressive cancer subtypes, as validated by immunohistochemistry and diverse cohort data. Furthermore, TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis. In vitro investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition, migration, invasion, and angiogenesis. These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway, which is modulated by IL-17A in human uveal melanoma MUM2B cells. This study elucidates, for the first time, the significant associations of TCF3 with DNA variation profiles, prognostic outcomes, and the TME in multiple cancer contexts. TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies, particularly in uveal melanoma.

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来源期刊
Acta biochimica et biophysica Sinica
Acta biochimica et biophysica Sinica 生物-生化与分子生物学
CiteScore
5.00
自引率
5.40%
发文量
170
审稿时长
3 months
期刊介绍: Acta Biochimica et Biophysica Sinica (ABBS) is an internationally peer-reviewed journal sponsored by the Shanghai Institute of Biochemistry and Cell Biology (CAS). ABBS aims to publish original research articles and review articles in diverse fields of biochemical research including Protein Science, Nucleic Acids, Molecular Biology, Cell Biology, Biophysics, Immunology, and Signal Transduction, etc.
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