Dataset Information

Copy number variations and expression of MPDZ are prognostic biomarkers for clear cell renal cell carcinoma.

ABSTRACT: The vital copy number variation (CNV) plays a crucial role in clear cell renal cell carcinoma (ccRCC). MPDZ inhibit cell polarity associate with osmotic pressure response and cancer-related biological processes. In order to clarify the role of the CNV of MPDZ in the progression of ccRCC, we analyzed the CNV and expression of MPDZ and prognosis in ccRCC patients from The Cancer Genome Atlas data portal. Notably, we found that the deletion of MPDZ was the common CNV, which was present in 28.65% of ccRCC patients. With the development of tumors, the percentage of MPDZ deletion increased significantly (19.38% in stage I; 20.00% in stage II; 40.94% in stage III; and 45.00% in stage IV). The deletion of MPDZ significantly increased ccRCC risk (P=0.0025). Low MPDZ expression associated with its deletion was significantly associated with adverse outcomes in ccRCC patients (P=0.0342). Furthermore, immunohistochemical analysis by tissue microarray showed that MPDZ was expressed at lower levels in tumor tissues compared with adjacent tissues (P<0.01). Kaplan-Meier survival curves showed that ccRCC patients with low MPDZ expression had significantly shorter survival than those with high MPDZ expression (P=0.002). These results indicated that low MPDZ expression associated with CNV is a potential biomarker for the prognosis of ccRCC patients.

SUBMITTER: Huang YS

PROVIDER: S-EPMC5667992 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Copy number variations and expression of MPDZ are prognostic biomarkers for clear cell renal cell carcinoma.

Huang Yong-Sheng YS Liu Wen-Bin WB Han Fei F Yang Jun-Tang JT Hao Xiang-Lin XL Chen Hong-Qiang HQ Jiang Xiao X Yin Li L Ao Lin L Cui Zhi-Hong ZH Cao Jia J Liu Jin-Yi JY

Oncotarget 20170812 45

The vital copy number variation (CNV) plays a crucial role in clear cell renal cell carcinoma (ccRCC). MPDZ inhibit cell polarity associate with osmotic pressure response and cancer-related biological processes. In order to clarify the role of the CNV of MPDZ in the progression of ccRCC, we analyzed the CNV and expression of MPDZ and prognosis in ccRCC patients from The Cancer Genome Atlas data portal. Notably, we found that the deletion of MPDZ was the common CNV, which was ...[more]

PMID: 29108259

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Project description:Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

Project description: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.

Dataset Information

Copy number variations and expression of MPDZ are prognostic biomarkers for clear cell renal cell carcinoma.

Publications

Copy number variations and expression of MPDZ are prognostic biomarkers for clear cell renal cell carcinoma.

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