Integrative Multi-Omics Analysis Identifies Transmembrane p24 Trafficking Protein 1 (TMED1) as a Potential Prognostic Marker in Colorectal Cancer

Simple Summary In this study, the expression and prognostic significance of the transmembrane p24 trafficking protein 1 (TMED1) in colorectal cancer were investigated by utilizing patient survival data and multi-omics datasets, including immunohistochemical staining, transcriptomics, and proteomics. The results indicated that TMED1, functioning as an oncogene, is upregulated in colorectal cancer and exhibits a significant association with an unfavorable prognosis. Furthermore, the downregulation of TMED1 was found to impact the cell cycle and apoptotic signaling pathways. Additionally, a positive correlation was identified between TMED1 and other members of the TMED family (TMED2, TMED4, TMED9, and TMED10) in colorectal cancer. The protein-protein interaction network analysis further indicated the potential influence of TMED1 on immune regulation. Consequently, TMED1 emerged as a promising candidate biomarker for assessing the progression and prognosis of colorectal cancer.Abstract Several TMED protein family members are overexpressed in malignant tumors and associated with tumor progression. TMED1 belongs to the TMED protein family and is involved in protein vesicular trafficking. However, the expression level and biological role of TMED1 in colorectal cancer (CRC) have yet to be fully elucidated. In this study, the integration of patient survival and multi-omics data (immunohistochemical staining, transcriptomics, and proteomics) revealed that the highly expressed TMED1 was related to the poor prognosis in CRC. Crystal violet staining indicated the cell growth was reduced after knocking down TMED1. Moreover, the flow cytometry results showed that TMED1 knockdown could increase cell apoptosis. The expression of TMED1 was positively correlated with other TMED family members (TMED2, TMED4, TMED9, and TMED10) in CRC, and the protein-protein interaction network suggested its potential impact on immune regulation. Furthermore, TMED1 expression was positively associated with the infiltration levels of regulatory T cells (Tregs), cancer-associated fibroblasts (CAFs), and endothelial cells and negatively correlated with the infiltration levels of CD4+ T cells, CD8+ T cells, and B cells. At last, the CTRP and GDSC datasets on the GSCA platform were used to analyze the relationship between TMED1 expression and drug sensitivity (IC50). The result found that the elevation of TMED1 was positively correlated with IC50 and implied it could increase the drug resistance of cancer cells. This research revealed that TMED1 is a novel prognostic biomarker in CRC and provided a valuable strategy for analyzing potential therapeutic targets of malignant tumors.