Integrated Methylation–Expression Profiling of Solute Carrier Genes Prioritizes Four Candidates for Further Evaluation in Early-Stage Colorectal Cancer

Abstract

Colorectal cancer (CRC) is frequently diagnosed beyond the earliest stages, underscoring the need for molecular changes detectable during early disease. Previous studies identified widespread differential methylation of solute carrier (SLC) genes in CRC; however, whether these alterations are accompanied by concordant expression changes at Stage I, and which SLC genes warrant further prioritization, remain unclear. We integrated a previously generated CRC methylome dataset comprising 2,277 differentially methylated probes mapped to 336 SLC genes with stage-stratified TCGA colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) gene-expression and promoter-methylation data through UALCAN. Twenty-eight genes showed significant changes in both molecular layers, and 15 retained canonical inverse methylation–expression relationships in Stage I CRC. Four genes were prioritized based on concordance across COAD and READ and supporting CRC evidence. SLC5A7 was downregulated and promoter-hypermethylated, with expression p = 1.88 × 10⁻⁵ (COAD) and 2.10 × 10⁻² (READ), and methylation p < 1 × 10⁻¹² and 3.12 × 10⁻³, respectively. In contrast, SLC7A5 was upregulated and hypomethylated (expression: 3.67 × 10⁻¹² and 4.02 × 10⁻⁷; methylation: 1.11 × 10⁻¹⁶ and 3.79 × 10⁻⁴), as were SLC39A10 (expression: 2.83 × 10⁻¹¹ and 1.97 × 10⁻⁸; methylation: 3.73 × 10⁻⁶ and 1.76 × 10⁻³) and SLC7A11 (expression: 2.92 × 10⁻⁸ and 3.06 × 10⁻²; methylation: <1 × 10⁻¹² and 3.00 × 10⁻⁴), with values reported for COAD and READ, respectively. By integrating promoter methylation with expression at Stage I, this study narrows previously reported SLC methylation alterations to four candidate genes showing concordant early-stage molecular dysregulation across colon and rectal cancer datasets. Together, these results prioritize four SLC genes for further functional and clinical validation in early-stage CRC. Their diagnostic utility remains to be established in independent cohorts.