A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer

Abstract

SLC2A3 is a membrane transporter that belongs to the solute carrier family, whose function includes transmembrane transport and glucose transmembrane transport activity. To clarify the expression and role of SLC2A3 in colorectal cancer (CRC), we analyzed the TCGA and GEO databases and found that SLC2A3 mRNA levels were significantly higher in CRC tissues than that in adjacent non-tumor tissues. Furthermore, high expression of SLC2A3 predicted poor overall survival and disease free survival for CRC patients. For validation, we collected 174 CRC samples and found that SLC2A3 expression was higher in CRC tissues than that in adjacent non-tumor colorectal mucosa tissues by immunohistochemistry staining. Further study showed that high expression of SLC2A3 was enriched in epithelial–mesenchymal transition (EMT) classical pathway, interferon-γ pathway by GSEA analysis enrichment, indicating that SLC2A3 may play a key role in the progression of CRC through EMT and immune response, which also has been validated by the global gene expression profiling of human CRC cell lines. The expression of SLC2A3 was positively correlated with CD4 and CD8+T cells by using TIMER and EPIC algorithm, respectively. SLC2A3 knockdown suppressed migration and inhibited the expression of Vimentin and MMP9 in CRC cell line SW480 and RKO. Meanwhile, PD-L1 expression was also significantly attenuated in SW480 and RKO cells transfected with SLC2A3 siRNA. The result suggests that SLC2A3 may be involved in the immune response of CRC by regulating PD-L1 immune checkpoint. In our series, SLC2A3 and PD-L1 positive expression was 74% (128/174) and 22% (39/174) of CRC, respectively. SLC2A3 expression was significantly associated with perineural invasion in CRC patients. In conclusion, SLC2A3 may play an important role in progression of CRC by regulating EMT and PD-L1 mediated immune responses.

Prognostic value of the ferroptosis-related gene SLC2A3 in gastric cancer and related immune mechanisms

“…A previous study in colorectal cancer showed that SLC2A3 could regulate the epithelial-mesenchymal transition (EMT) classical pathway and PD-L1-mediated immune responses (Gao et al, 2021), which was consistent with our research results. Unlike the findings of this study, the results of our functional enrichment analysis showed that SLC2A3 might be related to cytokine-cytokine receptor interaction, EMT, T cell receptor signaling pathway, B cell receptor signaling pathway, and immune checkpoints.…”

Identification and validation of EMT-immune-related prognostic biomarkers CDKN2A, CMTM8 and ILK in colon cancer

“…Gao et al revealed that SLC2A3 plays a significant role in the progression of colorectal cancer by affecting EMT and immune response. Furthermore, SLC2A3 may regulate the expression of PD-L1 [ 15 ]. An EMT signature performs well in predicting the overall survival, and the model is associated with immune infiltration, proving its potential role in regulating immune status [ 16 ].…”

Novel Immune-Related Ferroptosis Signature in Esophageal Cancer: An Informatics Exploration of Biological Processes Related to the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 Regulatory Network

“… Dai et al (2013) found that highly expressed miR-106a can hinder the effect of SLC2A3 and further inhibit cell proliferation and glycolysis in gliomas. In addition, the up-regulation of the SLC2A3 gene has also been observed to reduce the OS and Disease Free Survival of patients with colorectal cancer ( Gao et al, 2021 ). As a transcription factor that induces DNA damage, recombinant DNA damage inducible transcript 3 (DDIT3) can develop diseases through apoptosis and autophagy ( Liu H. et al, 2021 ).…”