Abstract
BACKGROUND: Colorectal cancer (CRC) is a significant global health concern due to its high incidence and increasing prevalence among younger individuals. The identification of reliable biomarkers is essential for improving diagnostic accuracy and optimizing therapeutic strategies. Isthmin 2 (ISM2), a member of the Isthmin protein family, is expressed in multiple tissues, but its specific role in tumorigenesis and cancer progression remains poorly understood. Aberrant ISM2 expression has been detected in several malignancies, suggesting its potential involvement in cancer biology. Consequently, exploring the role of ISM2 in CRC is of great significance. This study aimed to explore the role of ISM2 in CRC, including its expression patterns, clinical significance, association with immune infiltration, and functional mechanisms. METHODS: RNA transcriptome sequencing data and clinical data from 698 patients with CRC were retrieved from The Cancer Genome Atlas (TCGA) database to evaluate associations between ISM2 expression and clinicopathological parameters. Data were analyzed and visualized using R software, incorporating multiple databases such as TIMER. In parallel, in vitro experiments, including cell culture and transfection, were conducted to assess the role of ISM2, with protein expression evaluated through immunoblotting. RESULTS: Bioinformatics analysis revealed that ISM2 was significantly elevated in CRC tissues compared to normal tissues and was differentially expressed across multiple tumor types. ISM2 demonstrated potential as a biomarker for distinguishing tumor tissues from non-tumor tissues and was associated with clinicopathological parameters, including TUMOR-NODE-METASTASIs (TNM) staging. Elevated ISM2 expression correlated with poorer overall survival (OS) outcomes. Additionally, ISM2 expression was inversely correlated with the presence of immune cells, particularly with CD8(+) T cells. Functional partner genes differentially expressed along with ISM2 were also identified. Experimental findings indicated upregulation of ISM2 protein expression in three CRC lines. Silencing ISM2 via small interfering RNA (siRNA) suppressed the proliferation, migration, and invasion of SW1116 cells. CONCLUSIONS: ISM2 is overexpressed in CRC and is associated with clinicopathological features, prognosis, and immune infiltration. It holds potential as a prognostic biomarker; however, further research is needed to elucidate its underlying mechanisms and clinical implications.