Abstract：
Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.
摘要：
FANCD2的单纯质化是DNA损伤后范可尼贫血（FA）途径激活的核心步骤。以FANCD2为中心的FA途径中的缺陷不仅导致基因组不稳定,而且诱导肿瘤发生。目前,很少有研究研究FANCD2在肿瘤中的作用，尚未对FANCD2进行泛癌症研究。我们使用公共数据库和其他已发表的研究对FANCD2在癌症中的作用进行了全面分析。此外，我们评估了FANCD2在增殖中的作用，通过体外和体内实验研究肺腺癌细胞的迁移和侵袭，并探讨FANCD2在顺铂化疗耐药中的作用。我们通过流式细胞术研究了FANCD2对肺腺癌细胞细胞周期的调节作用。并通过西方印迹验证了这种效果。FANCD2表达在大多数TCGA肿瘤中升高,并且在肿瘤患者中显示出与不良预后强的正相关。此外,FANCD2表达与免疫浸润有很强的相关性,免疫检查点,肿瘤突变负荷（TMB），和微卫星不稳定性(MSI)，这些是免疫相关的特征，提示其可能是肿瘤免疫治疗的潜在靶点。我们进一步发现FANCD2显著促进细胞增殖,入侵,和肺腺癌细胞的迁移能力以及其促进癌细胞增殖的能力可能通过调节细胞周期来实现。通过分析FANCD2在不同肿瘤中的致癌作用，发现FANCD2是癌症治疗中潜在的生物标志物和治疗靶标。
