Deep pan-cancer analysis and multi-omics evidence reveal that ALG3 inhibits CD8+ T cell infiltration by suppressing chemokine secretion and is associated with 5-fluorouracil sensitivity.

α-1,3-mannosyltransferase (ALG3) holds significance as a key member within the mannosyltransferase family. Nevertheless, the exact function of ALG3 in cancer remains ambiguous. Consequently, the current research aimed to examine the function and potential mechanisms of ALG3 in various types of cancer. Deep pan-cancer analyses were conducted to investigate the expression patterns, prognostic value, genetic variations, single-cell omics, immunology, and drug responses associated with ALG3. Subsequently, in vitro experiments were executed to ascertain the biological role of ALG3 in breast cancer. Moreover, the link between ALG3 and CD8+ T cells was verified using immunofluorescence. Lastly, the association between ALG3 and chemokines was assessed using qRT-PCR and ELISA. Deep pan-cancer analysis demonstrated a heightened expression of ALG3 in the majority of tumors based on multi-omics evidence. ALG3 emerges as a diagnostic and prognostic biomarker across diverse cancer types. In addition, ALG3 participates in regulating the tumor immune microenvironment. Elevated levels of ALG3 were closely linked to the infiltration of bone marrow-derived suppressor cells (MDSC) and CD8+ T cells. According to in vitro experiments, ALG3 promotes proliferation and migration of breast cancer cells. Moreover, ALG3 inhibited CD8+ T cell infiltration by suppressing chemokine secretion. Finally, the inhibition of ALG3 enhanced the responsiveness of breast cancer cells to 5-fluorouracil treatment. ALG3 shows potential as both a prognostic indicator and immune infiltration biomarker across various types of cancer. Inhibition of ALG3 may represent a promising therapeutic strategy for tumor treatment.

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Science and Technology Project of Wenzhou payments were made to our institution.