DPEP1 Increases Drug Resistance in an ASCL2-Dependent Manner in Colon Cancer Cells and Correlates with Immune Cell Infiltration

Background: Dipeptidase 1 (DPEP1) is associated with several human cancers. However, its function in colon cancer remains unclear. Methods: : DPEP1 expression was analyzed by TCGA and GTEx pancancer data. Survival analysis was performed using the R survival package to assess the prognostic value of the DPEP1 expression level in colon cancer. DPEP1 enrichment analysis was conducted by the clusterProfiler R software package. Correlation analysis, differential expression analysis, and Venn analysis were used to obtain key genes. Correlation of DPEP1 or ASCL2 expression with immune cell infiltration in colon cancer was performed by TIMER and GSCA databases. qRT-PCR, Western blot, Co-immunoprecipitation, dual luciferase reporter experiments, and immunohistochemistry were used to explore the correlation between DPEP1 and ASCL2. MTT was used to evaluate the role of DPEP1 in colon cancer drug resistance. Results: : DPEP1 was overexpressed in various cancers, including colon cancer. High DPEP1 expression was negatively correlated with the disease-specific survival (DSS) and progression-free interval (PFI) but not significantly correlated with the overall survival (OS). Enrichment analysis showed that DPEP1 may be related to the Wnt signaling pathway and Hippo signaling pathway. Further analysis showed that DPEP1 and ASCL2 had a strong positive correlation, and both correlated with immune cell infiltration. Moreover, DPEP1 enhanced drug resistance in an ASCL2- dependent manner. Conclusions: : Our findings revealed that DPEP1 enhanced drug resistance in an ASCL2-dependent manner and correlated with immune infiltration in colon cancer.