Genome‐wide screening and cohorts validation identifying novel lncRNAs as prognostic biomarkers for clear cell renal cell carcinoma

2019 ◽  
Vol 121 (3) ◽  
pp. 2559-2570 ◽  
Author(s):  
Chuanjie Zhang ◽  
Da Huang ◽  
Ao Liu ◽  
Yang Xu ◽  
Rong Na ◽  
...  
BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Quan ◽  
Yuchen Bai ◽  
Yunbei Yang ◽  
Er Lei Han ◽  
Hong Bai ◽  
...  

Abstract Background The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. Methods Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes’ prognostic values of patients with ccRCC were analyzed by GEPIA database. Results A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. Conclusion These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets 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.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 428-428
Author(s):  
Banumathy Gowrishankar ◽  
Venkata Jaganmohan Thodima ◽  
Ana M. Molina ◽  
Charles Ma ◽  
Asha Guttapalli ◽  
...  

428 Background: About one-third of patients with clear cell renal cell carcinoma (ccRCC) exhibit metastasis at the time of diagnosis and show poor prognosis. The genetic and epigenetic alterations associated with metastasis in ccRCC have variably been studied, and their role in the metastatic process is unclear. The goals of the current study were to identify genomic copy number alterations (CNAs) associated with ccRCC metastasis and examine their clinical utility. Methods: In this IRB-approved study, genome-wide copy number profiling was performed on DNA from 144 ccRCC (81 primary and 63 metastatic lesions). Differential CNAs between primary and metastatic lesions and between different metastatic sites were identified using Fisher’s exact test. Associations between CNAs and overall survival (OS) were tested using the log rank statistic and Kaplan-Meier method. Genomic profiling data of 437 and 240 primary ccRCC (TCGA and PMID: 23797736, respecitively) were used for verification. Results: Between primary and metastatic lesions, 25 CNAs were significantly different (p<0.05). Of the 11 more frequent in metastatic lesions, nine retained significance when comparing stage IV and stage I TCGA ccRCC. For 368 TCGA locally-invasive tumors (stages I, II, and III), three CNAs (loss of 9p24.3-p13.3, 9p12-q11, and 9q21.12-q21.33) were associated with inferior survival (p=0.002). In the second dataset of 214 locally-invasive lesions, loss of 18q11.2-q23 correlated with shorter OS (p=0.025). Across metastatic lesions, nine CNAs were found to be significantly enriched in lung lesions and three in bone. In a subset of 127 ccRCC with known metastatic status at 5 years after diagnosis, two of these CNAs (gain of 7q36.1-36.3 in lung and loss of 22q13.2 in bone) were significantly enriched in the corresponding primary specimens. Conclusions: This study identified CNAs associated with ccRCC metastasis and common sites of metastasis that have the potential to serve as biomarkers to assist in better risk stratification of patients with this disease. Integrated analyses of genes mapping to the loci of genomic imbalance would further our understanding of the biology of metastasis in renal cancer.


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


PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e78452 ◽  
Author(s):  
Alessio Valletti ◽  
Margherita Gigante ◽  
Orazio Palumbo ◽  
Massimo Carella ◽  
Chiara Divella ◽  
...  

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1773-1790
Author(s):  
Zhenfei Xiang ◽  
Erdong Shen ◽  
Mingyao Li ◽  
Danfei Hu ◽  
Zhanchun Zhang ◽  
...  

2020 ◽  
Vol 7 ◽  
Author(s):  
Zhulin Wu ◽  
Yingzhao Zhang ◽  
Xiang Chen ◽  
Wanjun Tan ◽  
Li He ◽  
...  

Background: As cancer immunotherapy has become a hot research topic, the values of CXC chemokine receptors (CXCRs) in tumor microenvironment have been increasingly realized. More and more evidence showed that the aberrant expression of CXCRs is closely related to the prognosis of various cancers. However, prognostic values and the exact roles of different CXCRs in clear cell renal cell carcinoma (ccRCC) have not yet been elucidated.Methods: To further evaluate the potential of seven CXCRs as prognostic biomarkers for ccRCC, multiple online analysis tools, including ONCOMINE, UALCAN (TCGA dataset), Kaplan–Meier Plotter, MethSurv, cBioPortal, GEPIA, Metascape, and TIMER databases, were utilized in our research.Results: The mRNA expression of CXCR4/6/7 was significantly increased in ccRCC patients, and all CXCRs are remarkably related to tumor stage or grade of ccRCC. Higher levels of CXCR3/4/5/6 expression were correlated with worse overall survival (OS) in patients with ccRCC, while higher expression of CXCR2 was associated with better OS. 23.14% mutation rate (118/510) of CXCR1-7 was observed in ccRCC patients, and the genetic alterations in CXCRs were related to worse OS and progression-free survival in ccRCC patients. Additionally, 53 CpGs of CXCR1-7 showed significant prognostic values. For functional enrichment, our results showed that CXCRs and their similar genes may be involved in cancer-associated pathways, immune process, and angiogenesis, etc. Besides, CXCRs were significantly correlated with multiple immune cells (e.g., CD8+ T cell, CD4+ cell, and dendritic cell).Conclusion: This study explored the potential prognostic values and roles of the CXCRs in ccRCC microenvironment. Our results suggested that CXCR4 and CXCR6 could be the prognostic biomarkers for the patients with ccRCC.


Oncotarget ◽  
2017 ◽  
Vol 8 (45) ◽  
pp. 78713-78725 ◽  
Author(s):  
Yong-Sheng Huang ◽  
Wen-Bin Liu ◽  
Fei Han ◽  
Jun-Tang Yang ◽  
Xiang-Lin Hao ◽  
...  

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