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染色体凝聚调节因子2在肺腺癌中的预后价值及免疫浸润的综合分析

Comprehensive analysis of prognostic value and immune infiltration of Regulator of Chromosome Condensation 2 in lung adenocarcinoma.

作者信息

Lin Hai, Lin Guofu, Lin Lanlan, Yang Jiansheng, Yang Dongyong, Lin Qinhui, Xu Yuan, Zeng Yiming

机构信息

Department of Respiratory Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian province, 362000, China.

Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian province, 362000, China.

出版信息

J Cancer. 2024 Feb 11;15(7):1901-1915. doi: 10.7150/jca.91367. eCollection 2024.

Abstract

Lung adenocarcinoma (LUAD) incidence and mortality take the leading place of most malignancies. Previous studies have revealed the regulator of chromosome condensation 1 (RCC1) family members played an essential role during tumorigenesis. However, its biological functions in LUAD still need further investigation. Several databases were applied to explore potential effects of RCC1 family members on LUAD, such as Oncomine, GEPIA, and cBioPortal. Real-time PCR and immunohistochemistry were used to verify the expression of RCC2 in stage I LUAD. H1975 and A549 were selected to explore the biological function of RCC2 in cellular malignant phenotype. The expressions of RCC1 and RCC2 showed marked differences in malignant tissue compared to lung tissue. The higher the expression levels of RCC1 or RCC2 in LUAD patients, the shorter their overall survival (OS). In normal lung tissues, RCC1 expression was highly enriched in alveolar cells and endothelial cells. Compare with RCC1, RCC2 expression in normal lung tissue was significantly enriched in macrophages, B cells and granulocytes. Additionally, RCC2 expression level was correlated with multiple immune cell infiltration in LUAD. Moreover, the mutation or different sCNA status of RCC2 exerted influence on multiple immune cell infiltration distribution. We found that the upregulation of RCC1 and RCC2 were obviously related to TP53 mutation. GSEA analysis revealed that RCC2 was involved in the process of DNA replication, nucleotide excision repair and cell cycle, which might affect tumor progression through P53 signaling pathway. We further elucidated that downregulation of RCC2 could dramatically repress the migration and invasion of LUAD cells. The study demonstrated that RCC1 and RCC2 expression were markedly increased in early-stage of LUAD. Patients with high expression of RCC1 or RCC2 had a worse prognosis. Based on our analysis, RCC1 and RCC2 might exert influence on LUAD process through DNA replication, nucleotide excision repair and cell cycle, as well as cells migration and invasion. Different from RCC1, RCC2 also involved in immune infiltration. These analyses provided a novel insight into the identification of diagnostic biomarker.

摘要

肺腺癌(LUAD)的发病率和死亡率在大多数恶性肿瘤中位居首位。先前的研究表明,染色体凝聚调节因子1(RCC1)家族成员在肿瘤发生过程中起着至关重要的作用。然而,其在LUAD中的生物学功能仍需进一步研究。本研究应用多个数据库,如Oncomine、GEPIA和cBioPortal,来探究RCC1家族成员对LUAD的潜在影响。采用实时定量PCR和免疫组织化学方法验证RCC2在I期LUAD中的表达。选取H1975和A549细胞来探究RCC2在细胞恶性表型中的生物学功能。与肺组织相比,RCC1和RCC2在恶性组织中的表达存在显著差异。LUAD患者中RCC1或RCC2的表达水平越高,其总生存期(OS)越短。在正常肺组织中,RCC1表达在肺泡细胞和内皮细胞中高度富集。与RCC1相比,RCC2在正常肺组织中的表达在巨噬细胞、B细胞和粒细胞中显著富集。此外,RCC2表达水平与LUAD中多种免疫细胞浸润相关。而且,RCC2的突变或不同的体细胞拷贝数改变状态对多种免疫细胞浸润分布产生影响。我们发现RCC1和RCC2的上调明显与TP53突变有关。基因集富集分析(GSEA)显示,RCC2参与DNA复制、核苷酸切除修复和细胞周期过程,可能通过P53信号通路影响肿瘤进展。我们进一步阐明,RCC2的下调可显著抑制LUAD细胞的迁移和侵袭。该研究表明,RCC1和RCC2在LUAD早期表达明显增加。RCC1或RCC2高表达的患者预后较差。基于我们的分析,RCC1和RCC2可能通过DNA复制、核苷酸切除修复和细胞周期以及细胞迁移和侵袭对LUAD进程产生影响。与RCC1不同,RCC2还参与免疫浸润。这些分析为诊断生物标志物的鉴定提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c019/10905397/bf7b7f124b1b/jcav15p1901g001.jpg

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