SLC35D1 Is Associated with Colorectal Cancer Progression, EMT-Related Phenotypes, and Immune Infiltration

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and the prognosis of patients with metastatic disease remains poor. Solute carrier proteins participate in diverse cellular processes, yet the biological and clinical relevance of the SLC35D family in CRC remains largely unexplored. This study systematically investigated the expression patterns and clinical significance of SLC35D family members and further evaluated the functional role of SLC35D1 in CRC. Bioinformatic analyses using TCGA and other publicly available datasets and analytical platforms were performed to evaluate the expression patterns and clinical significance of SLC35D family members in CRC. Associations of SLC35D1 expression with patient survival, immune cell infiltration, immune checkpoint markers, and cancer-related transcriptional programs were examined. Loss- and gain-of-function experiments in CRC cells were performed to assess the effects of SLC35D1 on cell proliferation, migration, invasion, and EMT-related phenotypes. SLC35D1 expression was significantly decreased in CRC tissues, SLC35D2 showed a nonsignificant downward trend, and SLC35D3 was significantly increased. Lower SLC35D1 expression was associated with poorer clinical outcomes in the TCGA cohort, although this prognostic association was not reproduced in the independent GSE39582 cohort. Bioinformatic analyses further revealed associations between SLC35D1 expression and immune cell infiltration, immune checkpoint markers, and several cancer-related transcriptional programs. Although the association between SLC35D1 and the EMT-related signature was modest, pathway-enrichment analyses suggested a potential relationship with EMT-related processes. Consistent with these observations, loss- and gain-of-function studies showed that SLC35D1 expression was associated with changes in CRC cell proliferation, migration, invasion, and EMT-related molecular phenotypes. Our findings identify SLC35D1 as an understudied SLC35D family member associated with CRC progression and clinical outcome. Functional studies showed that modulation of SLC35D1 expression was associated with changes in malignant phenotypes in CRC cells, whereas its relationships with EMT-related programs and the tumor immune microenvironment warrant further mechanistic investigation. These findings suggest that SLC35D1 may have prognostic relevance in CRC, although its prognostic value requires further validation in independent clinical cohorts.