Integrating transcriptomics and scPagwas analysis predicts naïve CD4 T cell-related gene DRAM2 as a potential biomarker and therapeutic target for colorectal cancer.

Abstract

Objective: The interaction between T cells, particularly naïve CD4 T cells (CD4Tn), and colorectal cancer (CRC) is highly complex. CD4Tn play a crucial role in modulating immune responses within the tumor microenvironment, yet the precise mechanisms by which they influence tumor progression remain elusive. This study aims to explore the relationship between CRC and CD4Tn, identify biomarkers and therapeutic targets, and focus on the role of CD4Tn in shaping the immune environment of CRC.

Methods: Single-cell transcriptomics, alongside the scPagwas algorithm, were employed to identify pivotal T cell subsets involved in CRC progression. Bulk transcriptomic data were further analyzed using deconvolution algorithms to elucidate the roles of these key T cell subsets. The abundance of naïve CD4 T cells (CD4Tn) was specifically assessed to gauge patient responses to immunotherapy, alterations in the immune microenvironment, and correlations with genetic mutations. Key genes linked to CD4Tn were identified using weighted gene co-expression network analysis and Pearson correlation scores. The SMR algorithm was subsequently used for validation, with experimental verification following.

Results: Through single-cell transcriptomics and the scPagwas algorithm, CD4Tn was confirmed as a critical cell type in CRC progression. High infiltration of CD4Tn cells in CRC patients was correlated with poorer prognosis and suboptimal responses to immunotherapy. SMR analysis suggested a potential causal link between DRAM2 gene expression and CRC progression. Experimental knockdown of DRAM2 in colorectal cancer cells significantly inhibited tumor growth.

Conclusion: The DRAM2 gene, associated with CD4Tn cells, appears to play a pivotal role in the advancement of CRC and may represent a promising therapeutic target for treatment.