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Open Access 01-12-2023 | Hepatocellular Carcinoma | Research

FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma

Authors: Xiaowei Tang, Bei Luo, Shu Huang, Jiao Jiang, Yuan Chen, Wensen Ren, Xiaomin Shi, Wei Zhang, Lei Shi, Xiaolin Zhong, Muhan Lü

Published in: European Journal of Medical Research | Issue 1/2023

Abstract

Background

Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC.

Methods

The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein–protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed.

Results

Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia.

Conclusion

Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.

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Title: FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma
Authors: Xiaowei Tang
Bei Luo
Shu Huang
Jiao Jiang
Yuan Chen
Wensen Ren
Xiaomin Shi
Wei Zhang
Lei Shi
Xiaolin Zhong
Muhan Lü
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Hepatitis B
Sorafenib
Published in: European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-023-01411-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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