Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Current adjuvant chemotherapy regimens often lead to significant toxicities, so novel targets and targeted therapies are of great interest. Nischarin (NISCH, IR1, IRAS) is a non-adrenergic imidazoline-1 receptor protein that has been described as a tumor suppressor in breast and ovarian cancer. NISCH expression and its biological role in other types of cancer have not been investigated to date. Importantly, NISCH is a druggable target for which chemical agonists and antagonists have already been developed. The aim of this study was to examine the expression of nischarin in colon cancer and determine its potential role in disease progression and patient outcome.
The web resource for analyzing cancer transcriptome data from The Cancer Genome Atlas (TCGA) was used to analyze the NISCH mRNA expression levels in normal and colon cancer samples. Patients from the TCGA colon cancer database (n = 440) were divided into "high" and "low" groups based on mean NISCH expression and Kaplan-Meier survival analysis was performed. Gene Set Enrichment Analysis (GSEA) was performed on several publicly available datasets using the Hallmarks and KEGG gene sets to find gene expression signatures that correlate with NISCH expression.
In the TCGA database there was no significant difference in expression of NISCH between normal and tumor tissue (p > 0.05). Survival analysis showed that patients with higher NISCH tumor levels had significantly shorter overall survival (p = 0.0141, Log-rank test). In the GSE41258 dataset, levels of NISCH were higher in primary tumors of patients with M1 status compared to tumors of patients without metastasis (p = 0.027, unpaired t test). GSEA revealed that gene expression sets of epithelial-mesenchymal transition, angiogenesis, focal adhesion assembly and extracellular matrix-receptor interaction, all of which are associated with metastasis, were significantly correlated with NISCH expression in primary tumors.
In colon cancer, unlike in breast and ovary, higher NISCH expression might be associated with poor prognosis. Given that nischarin is a druggable target, it is potentially a new therapeutic target for selective treatment of patients with advanced colon cancer.
Institute for Oncology and Radiology of Serbia.
Has not received any funding.
All authors have declared no conflicts of interest.