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Background: Cholangiocarcinoma is a prevalent gastrointestinal tumor with limited effective early diagnostic methods. The role of neutrophils in the context of cholangiocarcinoma remains largely unexplored. Methods: A comprehensive analysis was performed on a cohort of cholangiocarcinoma samples (TCGA‐CHOL) from the TCGA database to investigate the relationship between cholangiocarcinoma and neutrophils. Methodologies included single‐sample gene set enrichment analysis (ssGSEA), differential expression analysis, weighted gene co‐expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). Results: The study identified a significant decrease of neutrophils in cholangiocarcinoma via ssGSEA. WGCNA and differential expression analysis led to the identification of a neutrophil‐related gene module comprised of 1059 genes. Cluster 1, showing a higher proportion of neutrophils, was linked to better survival outcomes. GSEA disclosed downregulation of complement, inflammatory response and interferon response pathways in Cluster 2, hinting at possible cholangiocarcinoma development triggers. A notable upregulation of PD1, PD‐L1 and CTLA4 was observed in Cluster 1, suggesting potential benefits from immunotherapy. A prognostic model was developed based on clinical data and expression levels of three prognostic genes (SOWAHD, TNFAIP8 and EBF3) showing satisfactory discrimination, calibration and clinical benefits. An overexpression of TNFAIP8 in cholangiocarcinoma cells was found, with its knockdown significantly inhibiting cell proliferation and migration. Conclusions: This study elucidates a neutrophil‐related gene module and prognostic genes, offering insights into the role of neutrophils in cholangiocarcinoma development and progression. It also introduces a clinical prediction model for enhanced prognosis assessment. These findings may lay the groundwork for the development of innovative therapeutic strategies in cholangiocarcinoma treatment. [ABSTRACT FROM AUTHOR]

Background: As the main cellular ingredients of tumor microenvironment, tumor-associated macrophages (TAMs) play a vital role in tumor development and progression. Recent studies have suggested that TAMs are sensitive and specific prognostic factors in numerous cancers. The primary purpose of this study is to determine the prognostic significance of TAMs in intrahepatic cholangiocarcinoma (ICC)., Methods: Immunohistochemical staining of CD68, CD86 and CD206 were performed in tissue microarrays containing 322 patients, who underwent surgical resection and were pathologically diagnosed with ICC. The prognostic value of CD68, CD86 and CD206 were evaluated by Kaplan-Meier analysis (log-rank test) and nomogram models., Results: We demonstrated that the CD86 + /CD206 + TAMs model was an independent prognostic index for ICC patients. Patients with low CD86 + TAMs and high CD206 + TAMs infiltration had a markedly worse prognosis and increased risk of post-operative recurrence when compared to high CD86 + TAMs and low CD206 + TAMs intratumoral infiltration. Furthermore, subgroup analysis indicated that the CD86 + /CD206 + TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. Interestingly, the CD86 + /CD206 + TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86 + /CD206 + TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients., Conclusions: These findings indicate that the CD86 + /CD206 + TAMs model possess potential value as a novel prognostic indicator for ICC patients., Competing Interests: The authors declare that they have no competing interests., (© 2020 Sun et al.)