scholarly journals Increased CDC6 Expression Associates With Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yao Yicong ◽  
Yi Wang ◽  
Wu Denglong ◽  
Hu Baoying

BackgroundCDC6 (Cell division control protein 6), located at chromosome 17q21.3, plays an important role in the early stage of DNA replication and has unique functions in various malignant tumors. Here, we evaluate the relationship between CDC6 expression and oncology outcomes in patients with clear cell renal cell carcinoma (ccRCC).MethodsA retrospective analysis of 118 ccRCC patients in Affiliated Hospital of Nantong University from 2015 to 2017 was performed. Triplicate tissue microarrays (TMA) were prepared from formalin-fixed and paraffin-embedded specimens. Immunohistochemistry (IHC) was conducted to evaluate the relationship between CDC6 expression and standard pathological features and prognosis. The RNA sequencing data and corresponding clinical information were acquired from the TCGA database. GSEA was used to identify signal pathways related to CDC6. Cox regression analysis was used to assess independent prognostic factors. In addition, the relationship between CDC6 and immunity was also investigated.ResultsThe results of Kaplan–Meier curve indicated that the OS of the patients with high expression of CDC6 was shorter than that of the patients with low CDC6 expression. Integrating the TCGA database and IHC staining, the results showed that CDC6 in ccRCC tissue was obviously up-regulated compared with adjacent normal kidney tissue. The results of Logistic regression analysis demonstrated that ccRCC patients with high expression of CDC6 are more likely to develop advanced disease than ccRCC patients with low CDC6 expression. The results of GSEA showed that the high expression of CDC6 was related to multiple signaling pathways. As for immunity, it was also related to TMB, immune checkpoint molecules, tumor microenvironment and immune infiltration. There were significantly correlations with CDC6 and immune cell infiltration levels and tumor microenvironment. The results of further results of the TCGA database showed that CDC6 was obviously related to immune checkpoint molecules and immune cells.ConclusionsIncreased expression of CDC6 is a potentially prognostic factor of poor prognosis in ccRCC patients.

2021 ◽  
Author(s):  
Shuaishuai Huang ◽  
Xiaodong Qing ◽  
Qiuzi Lin ◽  
Qiaoling Wu ◽  
Xue Wang ◽  
...  

Abstract Background: m6A RNA methylation and tumor microenvironment (TME) have been reported to play important roles in the progression and prognosis of clear cell renal cell carcinoma (ccRCC). However, whether m6A RNA methylation regulators affect TME in ccRCC remains unknown. Thus, the current study is designed to comprehensively evaluate the effect of m6A RNA methylation regulators on TME in ccRCC.Methods: Transcriptome data of ccRCC was obtained from The Cancer Genome Atlas (TCGA) database. Consensus clustering analysis was conducted based on the expressions of m6A RNA methylation regulators. Survival differences were evaluated by Kaplan-Meier (K-M) analysis between the clusters. DESeq2 package was used to analyze the differentially expressed genes (DEGs) between the clusters. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were analyzed by ClusterProfiler R package. Immune, stromal and ESTIMATE scores were assessed by ESTIMATE algorithm. CIBERSORT algorithm was applied to evaluate immune infiltration. The expressions of human leukocyte antigen (HLA), immune checkpoint molecules, and Th1/IFNγ gene signature associated with TME were also compared between the clusters. TIDE algorithm and subclass mapping were used to analyze the clinical response of different clusters to PD-1 and CTLA-4 blockade. Results: The expressions of fifteen m6A regulators were significantly different between ccRCC and normal kidney tissues. Based on the expressions of those fifteen m6A regulators, two clusters were identified by consensus clustering, in which cluster 1 had better overall survival (OS). A total of 4,429 DEGs were found between the two clusters, and were enriched into immune-related biological processes. Further analysis of the two clusters’ TME showed that cluster 1 had lower immune and ESTIMATE scores, higher expressions of HLA and lower expressions of immune checkpoint molecules. Besides, immune infiltration and the expressions of Th1/IFNγ gene signature also have significant differences between two clusters. Conclusions: Our study revealed that m6A regulators were important participants in the development of ccRCC, with a close relationship with TME.


PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0166231 ◽  
Author(s):  
Jianfeng Wang ◽  
Yunze Xu ◽  
Liangsong Zhu ◽  
Yun Zou ◽  
Wen Kong ◽  
...  

2019 ◽  
Vol 72 (5) ◽  
pp. 354-362 ◽  
Author(s):  
Qin Jin ◽  
Yanfeng Dai ◽  
Yan Wang ◽  
Shu Zhang ◽  
Gang Liu

AimsKinesin family member 11 (Kif11) is a member of the kinesin family motor proteins, which is associated with spindle formation and tumour genesis. In this study, we investigated the relationship between Kif11 expression and clear cell renal cell carcinoma (CCRCC) development.MethodsThe relationship between Kif11 expression and CCRCC development was analysed by quantitative real-time (qRT)-PCR analyses, and tissue immunohistochemistry. The prognostic significance of Kif11 expression was explored by univariable and multivariable survival analyses of 143 included patients. Furthermore, SB743921 was used as a specific Kif11 inhibitor to treat 786-O cells with the epithelial to mesenchymal transition (EMT) process analysed by qRT-PCR, and cell survival rates analysed with Annexin V-FITC/PI staining followed by flow cytometric analyses. Disease-free survival curves of Kif11 with different cancers and the relationships between Kif11 and the von Hippel-Lindau disease tumour suppressor gene (VHL), and proliferating cell nuclear antigen (PCNA) in kidney cancer were further analysed using the GEPIA database.ResultsThe levels of Kif11 mRNA were significantly higher in CCRCC tissues compared with corresponding non-cancerous tissues. The results of immunohistochemistry demonstrated that the expression of Kif11 protein was significantly associated with clinicopathologial parameters, including nuclear grade and TNM stage. The Kaplan-Meier survival curve indicated that high Kif11 expression, nuclear grade and TNM stage were independent factors to predict poor prognosis in patients with CCRCC. In addition, inhibition of Kif11 expression by SB743921 suppressed cell proliferation, migration and the EMT process with increased apoptosis rate.ConclusionsThese results combined with bioinformation analyses suggest that high Kif11 expression was associated with unfavourable prognosis in CCRCC and could be used as a potential prognostic marker in the clinical diagnosis of CCRCC.


2012 ◽  
Vol 5 (2) ◽  
pp. 473-478 ◽  
Author(s):  
CAN WEI ◽  
SONG WU ◽  
XIANXIN LI ◽  
YADONG WANG ◽  
RUI REN ◽  
...  

2020 ◽  
Author(s):  
Zhen‑Peng Zhu ◽  
Lan‑Ruo Lin ◽  
Tong‑De Lv ◽  
Chun‑Ru Xu ◽  
Tian‑Yu Cai ◽  
...  

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