Yu Xin, Li Bei, Li Wenge, Yuan Jingping, Sun Shengrong, Li Juanjuan
Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, 238 Ziyang Road, Wuhan, 430060, Hubei, People's Republic of China.
Department of Pathology, Renmin Hospital of Wuhan University, 238 Ziyang Road, Wuhan, 430060, Hubei, People's Republic of China.
Sci Rep. 2025 Jan 9;15(1):1446. doi: 10.1038/s41598-025-85255-0.
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.
目前乳腺癌的死亡率凸显了对更好的预后工具的需求;此外,LIM和钙调蛋白同源结构域1(LIMCH1)作为一种在癌症中具有双重作用的蛋白质,是一个很有前景的研究对象。本研究采用了一种综合方法,将癌症基因组图谱(TCGA)队列的生物信息学分析与临床免疫组织化学(IHC)队列数据相结合。我们分析了LIMCH1的表达模式、其与临床病理特征及预后的关联,以及其对肿瘤免疫微环境(TIME)的影响。利用功能注释和单细胞RNA测序(scRNA-seq)数据来探索潜在的分子机制。我们的分析表明,乳腺癌患者中LIMCH1的高表达与不良临床结果显著相关,并可作为独立的预后指标。功能注释揭示了与致癌作用和代谢重配置相关的途径,从而表明LIMCH1在肿瘤进展中的作用。此外,LIMCH1的表达与以M2巨噬细胞数量增加、CD8 + T细胞和NK细胞数量减少为特征的免疫抑制性TIME相关。最后,我们开发了一个纳入LIMCH1表达的列线图来预测总生存率,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种功能,从而突出了其作为预后指标和治疗干预手段的潜在效用。