Molecular and Immune Profiling of Sessile Serrated Adenomas/Polyps Reveals Prognostic Genes and Immune Cell Dynamics...

Sessile serrated adenomas/polyps (SSAPs) are precursor lesions in colorectal cancer (CRC) development, exhibiting unique molecular and immunological profiles. Understanding the molecular and immune signatures associated with SSAP tumourigenic potential is critical for improving early detection and prognosis. This study employed RNA sequencing data from SSAPs, adenomatous polyps (APs), hyperplastic polyps (HPs), and control samples. Differential gene expression analysis was conducted using DESeq2, followed by pathway enrichment analysis. Immune cell compositions were determined via computational deconvolution. Survival outcomes were assessed using Kaplan-Meier analysis and multivariate Cox proportional hazard models. A predictive gene panel was developed based on hazard ratios of key genes. SSAPs demonstrated elevated stemness and epithelial-mesenchymal transition (EMT) signatures, suggesting a potential tumourigenic capacity that warrants further investigation. The immune landscape of SSAPs was characterised by increased cytolytic activity, T-cell inflammation scores, and enrichment of immune cell subsets such as T lymphocytes, macrophages, and dendritic cells. Differentially expressed genes (C1QTNF8, SLC2A2, DEPP1, CST2, IFNE, ERFE, and HYAL4) were identified as genes significantly associated with CRC prognosis in the analyzed TCGA dataset. Multivariate Cox analysis revealed that IFNE (HR = 1.44, p = 0.018), ERFE (HR = 1.27, p = 0.008), and HYAL4 (HR = 1.43, p = 0.032) were associated with adverse survival outcomes. An exploratory predictive gene panel combining favourable and adverse prognostic genes was associated with stratification of patients into high- and low-risk groups and with overall survival (p = 0.0038). SSAPs exhibit distinct molecular and immunological features that may be associated with CRC progression. Key candidate genes and immune cell dynamics identified in this study may serve as a starting point for future experimental and clinical studies.