Abstract LB370: Exploring SLC35B family genes in colorectal carcinoma: Bioinformatics and functional insights into prognosis and therapy

Abstract

Abstract Colorectal carcinoma (CRC) poses a significant health challenge, with recent therapeutic advances yet to substantially improve long-term patient survival. Central to this study is the SLC35B gene family (SLC35B1-4), which encodes nucleotide sugar transporters essential to cellular membranes. Emerging research highlights a link between these transporters' dysfunction and the development and progression of tumors, yet the specific role of the SLC35B family in CRC remains unclear. Our investigation delves into the function of SLC35B genes in CRC, utilizing an integrated bioinformatics approach with databases like GENT2, TCGA, UALCAN, cBioportal, TIMER, and Kaplan-Meier plotter. Our analysis reveals a notable upregulation of SLC35B1/2/4 mRNA in CRC tissues compared to adjacent non-tumor tissues, with a concurrent downregulation of SLC35B3. Promoter methylation analysis shows increased methylation for SLC35B1/3/4, while SLC35B2 demonstrates decreased methylation. According to GEO and TCGA data, CRC patients exhibiting high SLC35B4 expression face lower survival rates. Multivariate Cox regression analysis confirms high SLC35B4 expression as an independent risk factor. Further, SLC35B4 expression correlates with increased infiltration of immune cells, particularly macrophages, and aligns positively with immune checkpoints such as CD274 and HAVCR2. In vitro assays link SLC35B4 to enhanced cancer cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT). In vivo, SLC35B4 knockdown leads to reduced tumor growth in mouse xenograft models. RNA sequencing identifies 241 genes differentially expressed in SLC35B4 knockdown compared to control cells, with Gene Set Enrichment Analysis (GSEA) associating SLC35B4 with the PI3K-Akt signaling pathway. In summary, our research sheds light on the SLC35B gene family's role in CRC, especially SLC35B4, highlighting its potential as both a prognostic marker and a therapeutic target in CRC, particularly through its involvement in the PI3K-Akt signaling pathway. Citation Format: Yu-Jia Chang, Chang-Chun Yang, Cheng-Chin Lee, Chien-Yu Huang. Exploring SLC35B family genes in colorectal carcinoma: Bioinformatics and functional insights into prognosis and therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB370.