High expression of CCDC6 in relation to unfavorable outcome and immune cells infiltration in hepatobiliary carcinoma

Abstract

Background:The diagnosis of hepatobiliary carcinoma includes both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the first and the second most common hepatobiliary malignancies, respectively. CCDC6 (coiled-coil domain-containing protein 6) is a protein that interacts with apoptosis and DNA damage response elements and is commonly detected in cells. The prognostic and biological roles of CCDC6 in hepatobiliary carcinoma remain unknown. Methods: We used data from UALCAN, GEPIA, TIMER, GeneMANIA, STRING and HPA databases to determine the prognostic values and biological functions of CCDC6 in HCC and CCA. We downloaded the original online data from TCGA and GEO databases and analyzed them with R 3.2.2. We also gathered clinical records from patients with HCC (n = 94) and iCCA (n = 99) in our hospital to explore associations between CCDC6 expression and hepatobiliary carcinoma using immunohistochemistry detection. We used KEGG, GO and GESA analyses to explore relative pathways of CCDC6 in HCC and CCA. In addition, we assessed correlations between CCDC6 expression and tumor-infiltrating immune cells using data from the TIMER and GEPIA databases. Finally, we assessed associations between CCDC6 and marker genes of tumor-infiltrated immune cells in HCC to confirm some of our findings. Results: The mRNA and protein expressions of CCDC6 were noticeably upregulated in HCC and CCA tissues as compared with the expressions in healthy control tissues. The high CCDC6 expression levels were significantly correlated with advanced tumor grades as well as poor prognosis in patients with HCC, but not in patients with CCA. Our functional enrichment analysis revealed that CCDC6 is mainly involved in cell cycle processes, gene transcription, and immune cell-related pathways. Moreover, we found that the CCDC6 levels were positively correlated with the presence of tumor-infiltrating immune cells, including macrophages, CD4+T cells and dendritic cells. Conclusion: CCDC6 expression was increased in hepatobiliary carcinoma tissues. High expressions of CCDC6 were significantly associated with clinical severity variables (especially with advanced cancer stages and pathological tumor grades) and poor prognoses in patients with HCC. CCDC6 upregulation is associated with histone acetylation and immune infiltration in hepatobiliary carcinoma. In addition, CCDC6 has the potential to be used as a predictive biomarker during targeting therapy and immunotherapy.

Uncovering the immune microenvironment and molecular subtypes of hepatitis B-related liver cirrhosis and developing stable a diagnostic differential model by machine learning and artificial neural networks

“…Nevertheless, in a particular study, heightened expression of CCDC6 exhibited a robust correlation with unfavorable prognoses in hepatobiliary cancer cases. Furthermore, a significant association was observed between the CCDC6 gene, its corresponding protein, and PPP4R1 ( Wu et al, 2022 ). The incidence of HCC was significantly higher in HBV-LC patients than in CHB non-cirrhotic patients ( Do et al, 2014 ; Zhang et al, 2023 ).…”

“…We also used the R package "pheatmap" and "ggplot2″ to create heat maps and volcano maps to visualize the DEGs (Song et al, 2022a;Song et al, 2022b). To investigate the enrichment levels of DEGs in different functional pathways, we performed gene set enrichment analysis (GSEA) on DEGs using the R package "clusterProfiler" (Zhong et al, 2022;Huang et al, 2023a;Zhao et al, 2023), and selected the five highest and lowest enriched functional pathways for visualization.…”