Cross-Platform Evaluation of a Tumor-Budding-Associated Gene Signature in Colorectal Cancer
Year: 2026
Type: preprint
Abstract: Spatial transcriptomics has identified AIF1, LIF, MRC1 , and TNC as enriched in tumor-budding (TB) regions of colorectal cancer. We investigated whether this TB-associated gene module could be detected in bulk transcriptomic data. Pairwise gene co-occurrence was analyzed in bulk RNA-seq (TCGA-COADREAD, n=547) and single-cell RNA-seq (GSE178341, n=26,057 cells) using Fisher’s exact tests with Benjamini-Hochberg correction. In bulk RNA-seq, pairwise fold-enrichments were weak (1.16–2.72x), with AIF1–LIF showing no significant association (FE=1.16x, FDR=0.31). In single-cell data, the same pairs showed 31–184.5x (all FDR < 8×10⁻³⁸). Total UMI counts provided no evidence of doublet artifacts explaining these co-detection patterns. Exploratory enhancer–promoter interaction analysis in HCT116 cells further suggested these genes are controlled differently. GOT1 and MDH1 , two malate–aspartate shuttle genes, showed lower expression in late-stage CRC (FDR ≤ 0.010). A bulk-derived risk score showed a modest association (Cox HR=1.21, p=0.021). Overall, TB-associated co-expression was more clearly detected at single-cell than bulk resolution, highlighting the importance of transcriptomic resolution when studying tumor-microenvironment-associated gene signatures.
Authors: Pritom Sarkar, Prapthi Sarkar
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7222708095