scholarly journals Decreased CDKL2 Expression in Clear Cell Renal Cell Carcinoma Predicts Worse Overall Survival

2022 ◽  
Vol 8 ◽  
Author(s):  
Zhan Chen ◽  
Yan Lv ◽  
Lu He ◽  
Shunli Wu ◽  
Zhuang Wu

Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal type of kidney cancer. Although differential expression of cyclin-dependent kinase-like 2 (CDKL2) has been reported to be associated with tumor progression in other cancers, its prognostic value, and potential mechanism in patients with ccRCC still remain unknown.Methods: Gene expression analysis was conducted using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and International Cancer Genome Consortium databases. Further, clinicopathologic analysis; Kaplan–Meier survival analysis; weighted gene co-expression network analysis; gene set enrichment analysis; gene ontology enrichment; methylation; and immune infiltration analyses were performed using TCGA-kidney renal clear cell carcinoma profiles. CDKL2 translational levels were analyzed using The Human Protein Atlas database.Results:CDKL2 expression was decreased in ccRCC samples retrieved from the four databases. Gender, survival status, histologic grade, clinical stage, TNM classification, and tumor status were closely related to CDKL2 expression. In addition, CDKL2 downregulation was an independent prognostic factor for poor prognosis in multivariate analysis. Enrichment analyses using multiple tests revealed that CDKL2 is not just closely related to immune response but this association is highly correlated as well. Further, we found that CDKL2 expression was significantly correlated with the infiltration levels of T cell CD4 memory resting; monocytes; macrophages M0, M1, and M2; dendritic cells resting; mast cells resting; plasma cells; T cell CD8; and T cell regulatory.Conclusion: This is the first report to study the expression of CDKL2 in ccRCC, wherein we suggest that decreased CDKL2 expression is closely correlated with poor prognosis in ccRCC. We consider that CDKL2 is a novel and potential prognostic biomarker associated with immune infiltrates in ccRCC.

2021 ◽  
Vol 10 ◽  
Author(s):  
Yongfeng Wang ◽  
Ci Yin ◽  
Lele Geng ◽  
Weiyang Cai

The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor infiltrating immune cells (TIICs) recruited to the cancer microenvironment. Clear cell renal cell carcinoma (ccRCC) immune microenvironment plays an important role in the tumorigenesis. This research investigated the characteristics of immune cell invasion of renal cell carcinoma and provided clues for future clinical implementation. Retrospectively, ccRCC gene expression was analyzed with appropriate clinicopathological data from the Cancer Genome Atlas (TCGA) and GEO database up to December 2019. The CIBERSORT algorithm, meta-analysis, principal component analysis (PCA), Single-Sample Gene Set Enrichment Analysis (ssGSEA) and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. We also focused on evaluating the association with TIICs subpopulations and clinical features and molecular subtypes. TIICs subpopulation, especially Macrophages subgroup, T follicular helper (Tfh) cells and CD8 T cells, all contribute to tumorigenesis. Unsupervised clustering analysis revealed that there existed two distinct TIICs subgroups with different survival patterns. TIICs are extensively involved in the pathogenesis and development of the ccRCC. Characterizing the composition of TIICs influences the metabolism of tumors, activity, level, stage, and survival of patients. Collectively, the TIIC analysis has the potential to assist in the assessment and selection of ccRCC prognosis and treatment.


2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Weiting Kang ◽  
Meng Zhang ◽  
Qiang Wang ◽  
Da Gu ◽  
Zhilong Huang ◽  
...  

Clear cell renal cell carcinoma (ccRCC) is the most common lethal subtype of renal cancer, and changes in tumor metabolism play a key role in its development. Solute carriers (SLCs) are important in the transport of small molecules in humans, and defects in SLC transporters can lead to serious diseases. The expression patterns and prognostic values of SLC family transporters in the development of ccRCC are still unclear. The current study analyzed the expression levels of SLC family members and their correlation with prognosis in ccRCC patients with data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), cBioPortal, the Human Protein Atlas (HPA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO). We found that the mRNA expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly lower in ccRCC tissues than in normal tissues and the protein expression levels of SLC22A6, SLC22A7, SLC22A13, and SLC34A1 were also significantly lower. Except for SLC22A7, the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were correlated with the clinical stage of ccRCC patients. The lower the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were, the later the clinical stage of ccRCC patients was. Further experiments revealed that the expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly associated with overall survival (OS) and disease-free survival (DFS) in ccRCC patients. High SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 expression predicted improved OS and DFS. Finally, GSE53757 and ICGC were used to revalidate the differential expression and clinical prognostic value. This study suggests that SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 may be potential targets for the clinical diagnosis, prognosis, and treatment of ccRCC patients.


2020 ◽  
Author(s):  
Wingkeung Yiu ◽  
Can-Xuan Li ◽  
Jie Chen

Abstract Background: Growing evidence has shown that the type VI collagen alpha chain (COL6A) family involved in the tumorigenesis and progression of diverse malignancies; however, its biological roles and potential mechanisms in clear cell renal cell carcinoma (ccRCC) remain unknown. The study was designed to explore the potential mechanisms and functions of COL6As in ccRCC.Methods: ONCOMINE and GEPIA databases were used to compare the transcriptional expression data of COL6As in ccRCC samples and normal renal samples. UALCAN database was utilized to determine the association between clinicopathological features and COL6As expression. Kaplan–Meier method was employed to determine the prognostic value of COL6As mRNA expression in ccRCC. CBioPortal database was used to investigate the genetic alterations of COL6As in ccRCC. Co-expression analyses, functional enrichment analyses, and gene set enrichment analysis (GSEA) were utilized to explore the potential action mechanisms of COL6As in ccRCC. Finally, we estimated the relationship between COL6As expression with immune cell infiltrates.Results: Upregulated transcriptional COL6A2/COL6A3 expression was observed in ccRCC specimens by comparison with noncancerous renal specimens. Patients with increased COL6A2/COL6A3 mRNA expression have a poor clinical outcome and unfavorable prognosis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analyses showed that COL6A2/COL6A3 might promote the tumorigenesis and progression of ccRCC by involving in several cancer-related pathways, such as axon guidance, focal adhesion, ECM receptor interaction. Besides, we found that COL6A2/COL6A3 expression was significantly associated with immune infiltration levels in ccRCC.Conclusions: COL6A2 and COL6A3 could act as candidate prognostic biomarkers and therapeutic targets in ccRCC. However, further experimental work was required to validate the conclusions.


Oncotarget ◽  
2016 ◽  
Vol 7 (31) ◽  
pp. 50017-50026 ◽  
Author(s):  
Tian Niu ◽  
Yidong Liu ◽  
Yuan Zhang ◽  
Qiang Fu ◽  
Zheng Liu ◽  
...  

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0216793 ◽  
Author(s):  
Agnieszka M. Borys ◽  
Michał Seweryn ◽  
Tomasz Gołąbek ◽  
Łukasz Bełch ◽  
Agnieszka Klimkowska ◽  
...  

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