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细胞分裂周期相关蛋白 5 表达水平升高预示着肝细胞癌患者的生存预后较差。

Higher expression of cell division cycle-associated protein 5 predicts poorer survival outcomes in hepatocellular carcinoma.

机构信息

Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.

出版信息

Aging (Albany NY). 2020 Jul 21;12(14):14542-14555. doi: 10.18632/aging.103501.

Abstract

The upregulation of cell division cycle associated protein 5 (CDCA5) has been observed in various cancer types. However, the prognostic value of CDCA5 and its underlying mechanism contributing to tumorigenesis in hepatocellular carcinoma (HCC) remain poorly understood. We used tissue microarray (TMA) to evaluate the prognosis of 304 HCC samples based on their CDCA5 expression, and analyzed the genomic features correlated with CDCA5 by using dataset from The Cancer Genome Atlas (TCGA). Compared with adjacent normal tissues, increased expression of CDCA5 was found in HCC tissues. Moreover, higher expression of CDCA5 was associated with inferior OS and DFS outcomes in HCC patients. The enrichment plots showed that the gene signatures in cell cycle, DNA replication and p53 pathways were enriched in patients with higher CDCA5 expression. Meanwhile, statistically higher mutations burdens in TP53 could also be observed in CDCA5-high patients. Integrative analysis based on miRNAseq and methylation data demonstrated a potential association between CDCA5 expression and epigenetic changes. In conclusion, our study provided the evidence of CDCA5 as an oncogenic promoter in HCC and the potential function of CDCA5 in affecting tumor microenvironment.

摘要

细胞分裂周期相关蛋白 5(CDCA5)的上调在各种癌症类型中都有观察到。然而,CDCA5 的预后价值及其在肝细胞癌(HCC)中促进肿瘤发生的潜在机制仍知之甚少。我们使用组织微阵列(TMA)根据 CDCA5 的表达评估了 304 例 HCC 样本的预后,并通过使用来自癌症基因组图谱(TCGA)的数据集分析了与 CDCA5 相关的基因组特征。与相邻正常组织相比,在 HCC 组织中发现 CDCA5 的表达增加。此外,CDCA5 表达水平较高的 HCC 患者的总生存期(OS)和无病生存期(DFS)更差。富集图显示,在 CDCA5 高表达的患者中,细胞周期、DNA 复制和 p53 途径的基因特征富集。同时,在 CDCA5-高患者中也可以观察到 TP53 突变负担统计学上更高。基于 miRNAseq 和甲基化数据的综合分析表明,CDCA5 表达与表观遗传变化之间存在潜在关联。总之,我们的研究提供了 CDCA5 作为 HCC 致癌促进子的证据,以及 CDCA5 在影响肿瘤微环境中的潜在功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/7425481/b67f8dce2d46/aging-12-103501-g001.jpg

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