关键词: Biomarker FANCA Immunity LIHC Prognosis

Mesh : Humans Carcinoma, Hepatocellular / genetics Fanconi Anemia Liver Neoplasms / genetics Blotting, Western Prognosis Fanconi Anemia Complementation Group A Protein / genetics

来  源:   DOI:10.1007/s10620-024-08282-3

Abstract:
BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a serious liver disease worldwide, and its pathogenesis is complicated.
OBJECTIVE: 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.
摘要:
背景:肝细胞癌(LIHC)是一种严重的肝脏疾病,其发病机制复杂。
目的:本研究探讨了FANCA在LIHC进展和预后中的潜在作用。
方法:公共数据库,定量逆转录聚合酶链反应(qRT-PCR),采用蛋白质印迹(WB)和免疫组织化学(IHC)测量肿瘤和正常样本之间的FANCA表达。检测FANCA表达与LIHC患者预后的关系。进行FANCA相关基因的功能富集。此外,我们进行了单因素和多因素分析,以确定LIHC中FANCA的独立预后价值.最后,FANCA基因敲除对增殖的影响,迁移,并通过克隆形成验证了HepG2细胞的侵袭,CCK8和Transwell测定。
结果:表达分析显示FANCA在LIHC组织和细胞中具有高表达水平。受试者工作特征(ROC)曲线分析显示FANCA在LIHC中具有重要的诊断价值。临床病理分析表明,FANCA在LIHC晚期表达明显高于早期。单变量,多变量,和Kaplan-Meier生存分析证实,FANCA的高表达与LIHC患者的低生存率密切相关.此外,LIHC中高水平的FANCA与免疫浸润的B细胞呈负相关,T细胞,和基质分数。此外,FANCA基因敲除显著抑制HepG2细胞增殖活性,迁移,和入侵能力。
结论:我们的数据显示,高水平的FANCA与LIHC恶性进展密切相关,暗示它作为诊断的潜在效用,预测指标,和治疗目标。
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