Fanconi Anemia Complementary Group A (FANCA) Facilitates the Occurrence and Progression of Liver Hepatocellular Carcinoma

• Published in: Digestive diseases and sciences 2024-03, Vol.69 (3), p.1035-1054
• Main Authors: Huang, Feng-die, Zhong, Yan-ping, Sun, Guang-yu, Xu, Qi-jiang, Xing, Zhi-yong, Chen, Ke-heng, Liao, Lu-sheng, Dong, Ming-you
• Format: Article
• Language: English
• Subjects: Biochemistry; Blotting, Western; Carcinoma, Hepatocellular - genetics; Fanconi Anemia; Fanconi Anemia Complementation Group A Protein - genetics; Gastroenterology; Hepatology; Humans; Liver cancer; Liver Neoplasms - genetics; Medical prognosis; Medicine; Medicine & Public Health; Oncology; Original Article; Prognosis; Survival analysis; Transplant Surgery
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-024-08282-3

Background Liver hepatocellular carcinoma (LIHC) is a serious liver disease worldwide, and its pathogenesis is complicated. Aims This study investigated the potential role of FANCA in the advancement and prognosis of LIHC. Methods Public databases, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunohistochemistry (IHC) were employed to measure FANCA expression between tumor and normal samples. The relationship between FANCA expression and prognosis of LIHC patients were examined. Functional enrichment of FANCA-related genes was performed. Furthermore, univariate and multivariate analyses were conducted to determine the independent prognosis value of FANCA in LIHC. Finally, influence of FANCA knockout on the proliferation, migration, and invasion of HepG2 cell was validated with cloning formation, CCK8, and Transwell assays. Results Expression analysis presented that FANCA had high expression level in LIHC tissues and cells. Receiver operating characteristic (ROC) curve analysis showed that FANCA was of great diagnosis value in LIHC. Clinicopathological analysis revealed that FANCA was significantly greater expressed in the advanced stage than in the early stage of LIHC. Univariate, multivariate, and Kaplan–Meier survival analysis confirmed that high expression of FANCA was strongly associated with poor survival of LIHC patients. In addition, high level of FANCA in LIHC showed a negative association with immunoinfiltrated B cells, T cells, and stromal scores. Moreover, Knockout of FANCA significantly inhibited HepG2 cell proliferative activity, migration, and invasion ability. Conclusions Our data revealed that high level of FANCA was closely associated with LIHC malignant progression, suggesting its potential utility as a diagnostic, predictive indicator, and therapeutic target.