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February 26, 2026International Journal of General Medicine0 citationsOpen Access

Comprehensive Analysis of the Expression and Prognostic Significance of NPAS1 in Patients with Colorectal Adenocarcinoma Based on Bioinformatics

MBMiaoyu BaiHarbin Medical University KHKeyi Hu JCJitao CuiTaizhou First People's Hospital

Key Points

This research aims to analyze the expression and prognostic significance of NPAS1 in colorectal adenocarcinoma (COAD).
Utilized data from TCGA and GEO for expression and clinicopathological analysis.
Validated NPAS1 expression in colon cancer tissues using Western blotting and immunohistochemical staining.
Performed bioinformatics analysis using GO, KEGG, GSEA, and ssGSEA for functional insights.
Examined methylation levels with UALCAN and mutation characteristics via cBioPortal.
Analyzed protein-protein interactions and transcription factor networks using STRING and Network Analyst.
NPAS1 expression was higher in normal tissues than in COAD tissues.
Higher NPAS1 expression correlated with better survival outcomes.
Finder related genes linked to various signaling pathways and immune cell infiltration types.
Elevated NPAS1 DNA methylation observed in tumor tissues compared to normal tissues.
Study provided insights into NPAS1's role in COAD etiology and management.

Abstract

Background: Neuronal PAS domain protein 1 (NPAS1) is a protein-coding gene expressed mainly in the central nervous system and plays a key role in nervous system development. The expression and prognostic value of NPAS1 in colorectal adenocarcinoma (COAD) are unknown. Methods: The expression and clinicopathological data of COAD from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. NPAS1 gene expression in colon cancer tissues was validated by Western blotting and immunohistochemical staining. Function and immune infiltration were established using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and single sample Gene Set Enrichment Analysis (ssGSEA). Methylation levels were analyzed utilizing the UALCAN database. NPAS1-related mutations were analyzed using cBioPortal. Single-cell and tissue-specific expression of NPAS1 was examined using the Human Protein Atlas. Protein-protein interactions and transcription factor networks of NPAS1-associated genes were analyzed with STRING and Network Analyst. Results: Our study found that the expression level of NPAS1 was higher in normal tissues compared to COAD tissues, higher NPAS1 expression was associated with better survival outcomes. The bioinformatics analysis confirmed that NPAS1 co-expressed genes were linked to diverse signalling pathways and cellular functions. NPAS1 is correlated with CD56bright, cytotoxic and NK cells, and negatively correlated with helper T cells and Tcm cells. The DNA methylation level of NPAS1 in tumor tissues was elevated compared to normal tissues. We analyzed the mutation characteristics of NPAS1, single-cell expression profiling of NPAS1, and protein-protein interactions involving genes associated with NPAS1. These discoveries offered perspectives on the etiology, identification, and management of COAD. Conclusion: This study revealed a significant decrease of NPAS1 expression in COAD tissues, exhibiting associations with the clinical stage, prognosis, immune infiltration, and DNA methylation of COAD. Keywords: colorectal adenocarcinoma, NPAS1, prognosis, immune infiltration, DNA methylation, gene mutation, single-cell RNAseq

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