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CDCA7的高表达预示着透明细胞肾细胞癌的预后不良,并探索其与免疫的关联。

High expression of CDCA7 predicts poor prognosis for clear cell renal cell carcinoma and explores its associations with immunity.

作者信息

Liu Shouyong, Wang Yi, Miao Chenkui, Xing Qianwei, Wang Zengjun

机构信息

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.

Department of Urology, Affiliated Hospital of Nantong University, No. 20 West Temple Road, Nantong, 226001, Jiangsu Province, China.

出版信息

Cancer Cell Int. 2021 Mar 1;21(1):140. doi: 10.1186/s12935-021-01834-x.

Abstract

BACKGROUND

Cell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive roles of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasize its associations with immunity.

METHODS

The RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated.

RESULTS

Our results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P < 0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P < 0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. Moreover, CDCA7 was significantly related to microsatellite instability (MSI, P < 0.001) and tumor mutational burden (TMB, P < 0.001). As for immunity, CDCA7 was remarkably associated with immune infiltration, tumor microenvironment, immune checkpoint molecules and immune pathways.

CONCLUSIONS

CDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to MSI, TMB, and immunity.

摘要

背景

细胞分裂周期相关7(CDCA7)作为细胞分裂周期相关家族的一员,据报道在实体瘤和血液系统肿瘤中均异常表达,提示其在促进肿瘤发生中起重要作用。因此,我们旨在探讨其在透明细胞肾细胞癌(ccRCC)中对总生存期(OS)的综合作用,并强调其与免疫的关联。

方法

从癌症基因组图谱(TCGA)数据库下载RNA测序数据及相应临床信息。采用基因集富集分析(GSEA)探索与CDCA7相关的信号通路。进行单因素和多因素Cox回归分析以评估独立预后因素。此外,还研究了CDCA7在人体免疫中的作用。

结果

我们的结果表明,CDCA7在ccRCC中高表达,其表达升高与较短的OS相关(P < 0.01)。单因素和多因素Cox回归分析均将CDCA7确定为独立预后因素(均P < 0.05)。构建了整合CDCA7表达水平和临床病理变量的预后列线图,以预测1年、3年和5年OS。GSEA表明,CDCA7高表达与凋亡途径、细胞周期途径、JAK-STAT途径、NOD样受体途径、P53途径、T细胞受体途径和Toll样受体途径等相关。此外,CDCA7与微卫星不稳定性(MSI,P < 0.001)和肿瘤突变负荷(TMB,P < 0.001)显著相关。至于免疫方面,CDCA7与免疫浸润、肿瘤微环境、免疫检查点分子和免疫途径显著相关。

结论

CDCA7可作为ccRCC的独立预后因素,且与MSI、TMB和免疫密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c05e/7923626/43fcf0dc3f0f/12935_2021_1834_Fig1_HTML.jpg

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