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Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system worldwide, and there is a lack of effective treatment for late-stage HCC. Recent experimental studies have demonstrated that dysfunction of the intestinal flora has a significant impact on hepatocarcinogenesis. The pathophysiological link between the intestine, its microbiota, and the liver has been described as the “gut-liver axis”. Dysbiosis of the intestinal flora and increased permeability of the intestinal wall are closely associated with liver pathology through the immune response. The “gut-liver axis” theory has been applied to the clinical study of the pathogenesis and treatment of HCC. The intestinal fungal community, as part of the gut microbiome, has a significant impact on human health and disease, while relatively little research has been done in HCC. In this study, we performed a comprehensive analysis of the expression and potential biological functions of the fungal recognition receptors C-type lectin receptors (CLRs) (Dectin-1, Dectin-2, Dectin-3, and Mincle) in HCC. We found that CLRs were downregulated in HCC, and their expressions were correlated with the clinical prognosis of HCC patients. Further studies suggested that the expression of CLRs were significantly correlated with immune infiltration and immunotherapy efficacy in HCC. Based on previous studies and our findings, we hypothesize that intestinal fungal communities and CLRs-triggered antifungal immunity have a key role in the pathogenesis of HCC, and these findings may provide new perspectives and targets for HCC immunotherapy.
Data Sharing Statement
The data used to support the results of this study are available from TCGA (https://portal.gdc.cancer.gov), the Assistant for Clinical Bioinformatics database (https://www.aclbi.com/static/index.html#/), and the TIMER platform (https://cistrome.shinyapps.io/timer/). Further inquiries can be directed to the corresponding authors.
Ethical Approval
All data for our study were obtained from public databases, as shown in the Material and Methods. Nevertheless, we need to state that all of our studies involving human data were performed in accordance with the Declaration of Helsinki and with the approval of the Committee on Ethics of Affiliated Drum Tower Hospital of Nanjing University Medical School. All patients who donated tissues have provided informed consent.
Acknowledgments
The authors would like to acknowledge the technical assistance provided by the staff of the Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. We would like to thank SpringNature for English language editing. The graphical figure was generated by Figdraw (www.figdraw.com).
Author Contributions
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.
Disclosure
The authors have declared that no competing interests exist.