High DDIT4 expression in colorectal cancer is associated with an immunosuppressive tumour microenvironment and poor prognosis

DNA damage-inducible transcript 4 (DDIT4) is a stress-responsive protein involved in immune activity and tumourigenesis, yet its relationship with the immune microenvironment of colorectal cancer (CRC) remains unclear. Using bioinformatics analysis of CRC datasets, in vitro cellular functional assays, and immunohistochemical evaluation of 65 clinical specimens, we investigated the role of DDIT4. Bioinformatics analysis revealed that DDIT4 is a key factor in CRC progression and prognosis, and it is closely associated with autophagy-related proteins, the EMT, and Immune response–related pathways. In vitro studies further confirmed that DDIT4 promotes the expression of ATG7 and enhances CRC cell migration and invasion. Immunohistochemistry revealed that compared with DDIT4-low tumours, DDIT4-high tumours exhibited elevated ATG7 ( p = 0.024) and PD-L1 ( p = 0.033) expression but reduced CXCL10 ( p = 0.036) expression. The DDIT4-high group displayed reduced T lymphocyte infiltration in both the tumour core (TC) and invasive margin (IM), especially in the TC, where pronounced decreases were observed in the CD3 + ( p = 0.001), CD4 + ( p = 0.040), and CD8 + ( p = 0.037) T-cell subsets. Our study demonstrated that high DDIT4 expression in CRC is associated with reduced tumour-infiltrating lymphocytes and increased tumour invasion. It serves as a biomarker for poor prognosis in patients with CRC and might be a potential target for adjuvant immune checkpoint inhibitor therapy.