Integrative bioinformatics and immunohistochemical analysis unravel the prognostic significance and immunological implication of LIMCH1 in breast cancer: a retrospective study

• Published in: Scientific reports 2025-01, Vol.15 (1), p.1446-15, Article 1446
• Main Authors: Yu, Xin, Li, Bei, Li, Wenge, Yuan, Jingping, Sun, Shengrong, Li, Juanjuan
• Format: Article
• Language: English
• Subjects: 631/67/1347; 631/67/1857; 631/67/580; 631/67/68; Bioinformatics; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Calponin; Carcinogenesis; CD8 antigen; Cell survival; Computational Biology - methods; Female; Gene Expression Regulation, Neoplastic; Genomic analysis; Homology; Humanities and Social Sciences; Humans; Immunohistochemistry; LIM Domain Proteins - genetics; LIM Domain Proteins - metabolism; LIMCH1; Lymphocytes T; Macrophages; Medical prognosis; Microenvironments; Middle Aged; Molecular modelling; multidisciplinary; Prognosis; Retrospective Studies; Science; Science (multidisciplinary); Therapeutic target; Tumor Microenvironment - immunology; Tumors; Tumour immunity
• ISSN: 2045-2322; 2045-2322
• 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.