RESUMO
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.
Assuntos
Carcinogênese , Proteína do Grupo de Complementação D2 da Anemia de Fanconi , Neoplasias , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Carcinogênese/genética , Dano ao DNA , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Neoplasias/genética , Neoplasias/patologiaRESUMO
Background and Objective: As a surgical tool, indocyanine green (ICG) is increasingly used in surgery, especially in gastric and colorectal surgery. The use of ICG fluorescence imaging can improve the accuracy of tumor resection and potentially improve surgical outcomes for cancer patients. However, there are still different opinions or controversies on the application of ICG in the literature and the administration of ICG is still not uniform. In this review, we summarize the current status of its application and ICG administration methods in gastrointestinal cancer and discuss its existing limitations and future research directions. Methods: Literature published in the PubMed database from 1969 to 2022 was searched for using the keywords "Indocyanine green or near-infrared imaging or ICG", "gastric cancer", "gastroesophageal junction cancer", and "colorectal cancer" to summarize the main applications of ICG in gastrointestinal cancers. Key Content and Findings: ICG guidance can rapidly determine tumor location and save operative time, and can also visualize lymph nodes (LNs) in real-time, helping surgeons to retrieve more LNs for better postoperative staging, but its use in identifying sentinel lymph node (SLN) in gastric cancer (GC) remains controversial due to false negatives. ICG fluorescent angiography has great potential in preventing colorectal anastomotic leakage, but there is a dearth of high-caliber research evidence. In addition, ICG has unique advantages in detecting colorectal liver micrometastasis. Notably, there is still no uniform administration method and dose of ICG. Conclusions: In this review, we summarize the current status of ICG application in gastrointestinal cancer, and the current literature suggests that it is safe and effective and has the potential to change the clinical outcome of patients. Therefore, ICG should be routinely used in gastrointestinal cancers to improve the surgical outcomes of patients. In addition, this review summarizes the ICG administration in the literature, and we expect future guidelines to unitize and standardize the administration of ICG.