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Expression of pre-selected TMEMs with predicted ER localization as potential classifiers of ccRCC tumors
Tomasz Wrzesiński1, Malgorzata Szelag2, Wojciech A Cieślikowski3
1Laboratory of High Throughput Technologies, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Umultowska 89, 61-614, Poznan, Poland. twrzes@amu.edu.pl.
Background:
VHL inactivation is the most established molecular characteristic of clear cell renal cell carcinoma (ccRCC), with only a few additional genes implicated in development of this kidney tumor. In recently published ccRCC gene expression meta-analysis study we identified a number of deregulated genes with limited information available concerning their biological role, represented by gene transcripts belonging to transmembrane proteins family (TMEMs). TMEMs are predicted to be components of cellular membranes, such as mitochondrial membranes, ER, lysosomes and Golgi apparatus. Interestingly, the function of majority of TMEMs remains unclear. Here, we analyzed expression of ten TMEM genes in the context of ccRCC progression and development, and characterized these proteins bioinformatically.
Methods:
The expression of ten TMEMs (RTP3, SLC35G2, TMEM30B, TMEM45A, TMEM45B, TMEM61, TMEM72, TMEM116, TMEM207 and TMEM213) was measured by qPCR. T-test, Pearson correlation, univariate and multivariate logistic and Cox regression were used in statistical analysis. The topology of studied proteins was predicted with Metaserver, together with PSORTII, Pfam and Localizome tools.
Results:
We observed significant deregulation of expression of 10 analyzed TMEMs in ccRCC tumors. Cluster analysis of expression data suggested the down-regulation of all tested TMEMs to be a descriptor of the most advanced tumors. Logistic and Cox regression potentially linked TMEM expression to clinical parameters such as: metastasis, Fuhrman grade and overall survival. Topology predictions classified majority of analyzed TMEMs as type 3 and type 1 transmembrane proteins, with predicted localization mainly in ER.
Conclusions:
The massive down-regulation of expression of TMEM family members suggests their importance in the pathogenesis of ccRCC and the bioinformatic analysis of TMEM topology implies a significant involvement of ER proteins in ccRCC pathology.
Insights
Transmembrane proteins (TMEMs) show significant down-regulation in clear cell renal cell carcinoma (ccRCC), indicating their potential role in kidney cancer progression and survival. Further analysis suggests ER proteins are involved in ccRCC pathology.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is characterized by VHL inactivation, with other contributing genes largely unknown.
- Gene expression meta-analysis identified deregulated transmembrane protein genes (TMEMs) in ccRCC with unclear functions.
- TMEMs are membrane proteins potentially located in mitochondria, ER, lysosomes, and Golgi apparatus.
Purpose of the Study:
- To analyze the expression of ten TMEM genes in ccRCC progression.
- To characterize the bioinformatic properties and cellular localization of these TMEM proteins.
Main Methods:
- Quantitative PCR (qPCR) was used to measure the expression of ten specific TMEM genes.
- Statistical analyses included T-test, Pearson correlation, and logistic/Cox regression.
- Protein topology and cellular localization were predicted using bioinformatics tools (Metaserver, PSORTII, Pfam, Localizome).
Main Results:
- Significant deregulation of all ten analyzed TMEMs was observed in ccRCC tumors.
- Down-regulation of TMEMs correlated with advanced tumor stage.
- TMEM expression was linked to clinical parameters like metastasis, Fuhrman grade, and overall survival.
- Bioinformatic analysis predicted most TMEMs as type 3 or type 1 transmembrane proteins, primarily localized in the ER.
Conclusions:
- Massive down-regulation of TMEMs suggests their critical role in ccRCC pathogenesis.
- Bioinformatic analysis indicates significant involvement of ER-localized proteins in ccRCC pathology.
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