Neutrophils and their related gene expression may play an important role in the prognosis of cholangiocarcinoma (CCA), according to a study published in The Journal of Gene Medicine.

Single-sample gene set enrichment analysis (ssGSEA) of CCA samples from The Cancer Genome Atlas (TCGA) database revealed that neutrophil numbers were significantly decreased in these patients. Differential expression analysis of 16,866 genes identified a smaller subset of 1059 genes that appeared to be related to neutrophils in CCA.

A subset of 8 genes with significant prognostic values was identified following gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, STRING online network analysis, and single-factor Cox regression analysis of the 1059 genes.

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Cluster analysis investigating the expression levels of the 8 genes—LING03, EBF3, ALOX5, CELF2, PITPNC1, TNFAIP8, GMIP, and SOWAHD—found that the cluster of patients with better survival (Cluster 1) also tended to have higher expression of these genes. These results indicate that a higher proportion of neutrophils could improve the survival prognosis of patients with CCA.

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Further analysis of the patient subgroup clusters revealed that tumor purity and the immune microenvironment were more active in Cluster 1.

The complement, inflammatory response, and interferon response pathways were all significantly downregulated in the cluster with poorer prognosis (Cluster 2). In contrast, expression of PD1, PD-L1, and CTLA4, classic immune checkpoint molecules, were all upregulated in Cluster 1, indicating that immunotherapy may be beneficial for this subgroup.

SOWAHD, TNFAI8, and EBF3 genes were further identified as potential prognostic biomarkers for bile duct cancer, with their protein interactions possibly playing a role in the development and progression of the disease.

“We identified several differentially expressed genes between tumor and normal tissues and identified three genes (SOWAHD, TNFAIP8, and EBF3) that were significantly associated with overall survival. We developed a prognostic model based on the expression of these genes and demonstrated its efficacy in predicting survival outcomes,” the authors wrote.

“These findings could potentially influence the clinical management of CCA, providing a stronger foundation for future exploration of the molecular mechanisms of this disease,” they noted.

A total of 35 CCA samples and 9 adjacent normal samples were collected from the TCGA database and utilized during the study.


Li J, Xiong J, Wei L, Zhang M, Yi J, Liu L. Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma. J Gene Med. Published online August 2, 2023. doi:10.1002/jgm.3569