Bioinformatic and Clinical Analysis Identifies Candidate Immune‐Regulatory Genes in Gallbladder Cancer

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Background Gallbladder cancer (GBC) exhibits a complex interplay with immune infiltration. This study is aimed at identifying exploratory immune‐associated candidate genes in GBC. Methods We analyzed gene expression datasets (GSE76633 and GSE74048) to identify differentially expressed genes (DEGs). Feature genes were selected through weighted gene coexpression network analysis (WGCNA), intersection with immune‐related gene sets, and machine learning approaches. A nomogram was constructed, and its performance was evaluated using receiver operating characteristic (ROC) analysis. Alterations in candidate genes were validated by qRT‐PCR in clinical samples. Results Among 3076 DEGs, we identified 11 immune‐related DEGs, which were further narrowed down to three feature genes: UNC93B1 , MARCO , and PIK3R1 . The resulting nomogram demonstrated high apparent predictive accuracy in the training cohort. UNC93B1 and PIK3R1 showed high apparent accuracy in the training cohort, with ROC AUCs reaching 1.000 for UNC93B1 , whereas validation cohort AUCs reached up to 0.970 for PIK3R1 . UNC93B1 expression correlated positively with T helper 2 (Th2) cells and negatively with monocytes, T follicular helper (Tfh) cells, and neutrophils, suggesting a potential association with a Th2‐skewed and myeloid/Tfh‐imbalanced tumor microenvironment, although these associations require further validation. In contrast, MARCO and PIK3R1 exhibited opposing correlation patterns. PIK3R1 showed database‐derived associations with several compounds. qRT‐PCR in three paired clinical samples showed expression patterns consistent with the GEO datasets. Conclusion UNC93B1 , MARCO , and PIK3R1 represent exploratory immune‐associated candidate genes in GBC and are associated with immune cell infiltration. Their distinct immune‐related correlation patterns, including the association of UNC93B1 with Th2 enrichment and myeloid/Tfh imbalance, are hypothesis‐generating and require further biological and functional validation.

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