RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Integrative bioinformatics and immunohistochemical analysis unravel the prognostic significance and immunological implication of LIMCH1 in breast cancer: a retrospective study.
Integrative bioinformatics and immunohistochemical analysis unravel the prognostic significance and immunological implication of LIMCH1 in breast cancer: a retrospective study.
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目前乳腺癌的死亡率凸显了对更好预后工具的需求;此外,LIM和calponin homology domain 1 (LIMCH1)是一种在癌症中具有双重作用的蛋白,是一个有前景的研究候选对象。
本研究采用了一种整合方法,结合了对The Cancer Genome Atlas (TCGA)队列的生物信息学分析以及临床免疫组织化学(IHC)队列数据。
我们分析了LIMCH1的表达模式、其与临床病理特征和预后的关联,以及其对肿瘤免疫微环境(TIME)的影响。功能注释和单细胞RNA测序(scRNA-seq)数据被用于探索潜在的分子机制。
我们的分析显示,乳腺癌患者中LIMCH1高表达与不良临床结局显著相关,并可作为独立预后指标。功能注释揭示了与癌变和代谢重编程相关的通路,从而提示LIMCH1在肿瘤进展中的作用。
此外,LIMCH1表达与免疫抑制性TIME相关,其特征为M2巨噬细胞数量增加以及CD8 + T细胞和NK细胞数量减少。最后,我们开发了一个纳入LIMCH1表达以预测总生存率的列线图,从而提供了一个临床适用的工具。
我们的研究阐明了LIMCH1在乳腺癌发病机制中的多样功能,从而突出了其作为预后指标和治疗干预的潜在用途。
The current mortality rates for breast cancer underscore the need for better prognostic tools; moreover, LIM and calponin homology domain 1 (LIMCH1), which is a protein with dual roles in cancer, is a promising candidate for investigation.
This study employed an integrative approach combining bioinformatics analysis of The Cancer Genome Atlas (TCGA) cohort and clinical immunohistochemistry (IHC) cohort data.
We analysed LIMCH1 expression patterns, its associations with clinicopathological features and prognosis, and its impact on the tumour immune microenvironment (TIME). Functional annotations and single-cell RNA sequencing (scRNA-seq) data were used to explore the underlying molecular mechanisms.
Our analysis revealed that high LIMCH1 expression in breast cancer patients was significantly associated with unfavourable clinical outcomes and served as an independent prognostic indicator. The functional annotations revealed pathways related to carcinogenesis and metabolic reconfiguration, thus suggesting the role of LIMCH1 in tumour progression.
Additionally, LIMCH1 expression was correlated with an immunosuppressive TIME characterized by increased numbers of M2 macrophages and reduced numbers of CD8 + T cells and NK cells.
Finally, we developed a nomogram incorporating LIMCH1 expression for predicting overall survival rates, thus providing a clinically applicable tool.
Our research elucidates the diverse functions of LIMCH1 in the pathogenesis of breast cancer, thus highlighting its potential utility as both a prognostic indicator and a therapeutic intervention.
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