scholarly journals The Choice of Candidates in Survival Markers Based on Coordinated Gene Expression in Renal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Natalya Apanovich ◽  
Pavel Apanovich ◽  
Danzan Mansorunov ◽  
Anna Kuzevanova ◽  
Vsevolod Matveev ◽  
...  
Keyword(s):  
Tumor Development ◽  
Initial Increase ◽  
Cell Renal Cell Carcinoma ◽  
Survival Prognosis ◽  
Expression Levels ◽  
Gene Group ◽  
Prediction Of Survival ◽  
Individual Survival ◽  
Inflammatory Processes ◽  
Shed Light

We aimed to identify and investigate genes that are essential for the development of clear cell renal cell carcinoma (ccRCC) and sought to shed light on the mechanisms of its progression and create prognostic markers for the disease. We used real-time PCR to study the expression of 20 genes that were preliminarily selected based on their differential expression in ccRCC, in 68 paired tumor/normal samples. Upon ccRCC progression, seven genes that showed an initial increase in expression showed decreased expression. The genes whose expression levels did not significantly change during progression were associated mainly with metabolic and inflammatory processes. The first group included CA9, NDUFA4L2, EGLN3, BHLHE41, VWF, IGFBP3, and ANGPTL4, whose expression levels were coordinately decreased during tumor progression. This expression coordination and gene function is related to the needs of tumor development at different stages. Specifically, the high correlation coefficient of EGLN3 and NDUFA4L2 expression may indicate the importance of the coordinated regulation of glycolysis and mitochondrial metabolism. A panel of CA9, EGLN3, BHLHE41, and VWF enabled the prediction of survival for more than 3.5 years in patients with ccRCC, with a probability close to 90%. Therefore, a coordinated change in the expression of a gene group during ccRCC progression was detected, and a new panel of markers for individual survival prognosis was identified.

scholarly journals Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1041
Author(s):  
Mohammad Tarek ◽  
Hana Abdelzaher ◽  
Firas Kobeissy ◽  
Hassan A. N. El-Fawal ◽  
Mohammed M. Salama ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Factors ◽  
Bioinformatics Analysis ◽  
Expression Patterns ◽  
Spike Protein ◽  
Target Cells ◽  
Health Crisis ◽  
Expression Levels ◽  
Different Populations ◽  
Shed Light

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2’s receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN’s potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

New mimetic peptides of the kinase-inhibitory region (KIR) of SOCS1 through focused peptide libraries

2012 ◽  
Vol 443 (1) ◽  
pp. 231-240 ◽  
Author(s):  
Nunzianna Doti ◽  
Pasqualina L. Scognamiglio ◽  
Stefania Madonna ◽  
Claudia Scarponi ◽  
Menotti Ruvo ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Catalytic Site ◽  
Janus Kinase ◽  
Scanning Method ◽  
Expression Levels ◽  
Interferon Regulatory Factor 1 ◽  
Inhibitory Region ◽  
Inflammatory Processes ◽  
Cytokine Stimulation ◽  
Kinase Inhibitory Region

SOCS (suppressor of cytokine signalling) proteins are negative-feedback regulators of the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway. Their expression levels are low under physiological conditions, but they are up-regulated in response to cytokine stimulation in many immune and inflammatory processes. Overexpression of SOCS1 in keratinocyte clones abrogates the IFNγ (interferon γ)-induced expression of many pro-inflammatory genes and the release of related chemokines by blocking the JAK/STAT pathway. SOCS1 inhibits JAK2 kinase activity by binding the catalytic site of JAK2, with its KIR (kinase-inhibitory region) acting as a pseudo-substrate of the enzyme. In the present study, we screened a focused combinatorial peptide library of KIR to identify new peptides able to mimic its function with an improved affinity towards the JAK2 catalytic site. Using an alanine-scanning method, KIR residues that are crucial for the interaction with JAK2 were unveiled. In this way, the KIR sequence was restricted to a shorter segment and ‘non-essential’ residues were replaced by different amino acids following a simplified combinatorial approach. We selected a new unnatural sequence able to bind to JAK2 with Kd values in the nanomolar range. This peptide was tested in human keratinocyte cultures and reduced the phosphorylation of STAT1 and the expression levels of IRF-1 (interferon regulatory factor-1).

scholarly journals Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Daniel Vergho ◽  
Susanne Kneitz ◽  
Andreas Rosenwald ◽  
Charlotte Scherer ◽  
Martin Spahn ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Expression Levels

scholarly journals Expression levels of caspase-3 and gasdermin E and their involvement in the occurrence and prognosis of lung cancer

2021 ◽  
Author(s):  
yuanli huang ◽  
GuangHui Zhang ◽  
Qing Zhu ◽  
Xia Wu ◽  
LIGao Wu
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Clinical Stage ◽  
The Body ◽  
Caspase 8 ◽  
Survival Prognosis ◽  
Expression Levels ◽  
Protein Levels ◽  
Normal Tissues ◽  
Related Proteins

Abstract Background Pyroptosis plays a dual role in the development of cancer and malignancy, and as such, may potentially be a new target for cancer treatment. However, the inflammatory response to pyroptosis may have adverse effects on the body. The roles of gasdermin E (GSDME), caspases, and related proteins associated with pyroptosis in cancer remain controversial. This study aimed to explore whether the expression levels of caspase-3 and GSDME affect the clinical stage, pathological grade, and survival prognosis of patients with lung cancer. Methods We examined the protein levels of GSDME, caspase-3, caspase-8, and caspase-9 in lung tissues from 100 patients with lung cancer by using immunohistochemistry. Results We found that GSDME, caspase-3, and caspase-8 were more highly expressed in the tumor tissues than in the adjacent normal tissues. Moreover, we found that GSDME could serve as a prognostic factor because there was a positive correlation between its expression level and the postoperative survival rate of patients with lung cancer. Conclusions GSDME may be an independent factor affecting the prognosis of patients with lung cancer. However, the role of GSDME and its related proteins in cancer requires further research.

scholarly journals N-Glycomic and Transcriptomic Changes Associated with CDX1 mRNA Expression in Colorectal Cancer Cell Lines

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 273 ◽  
Author(s):  
Stephanie Holst ◽  
Jennifer Wilding ◽  
Kamila Koprowska ◽  
Yoann Rombouts ◽  
Manfred Wuhrer
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Development ◽  
Cancer Cell Lines ◽  
Expression Levels ◽  
Nuclear Factors ◽  
Homeobox Protein ◽  
Regulated Gene Expression

The caudal-related homeobox protein 1 (CDX1) is a transcription factor, which is important in the development, differentiation, and homeostasis of the gut. Although the involvement of CDX genes in the regulation of the expression levels of a few glycosyltransferases has been shown, associations between glycosylation phenotypes and CDX1 mRNA expression have hitherto not been well studied. Triggered by our previous study, we here characterized the N-glycomic phenotype of 16 colon cancer cell lines, selected for their differential CDX1 mRNA expression levels. We found that high CDX1 mRNA expression associated with a higher degree of multi-fucosylation on N-glycans, which is in line with our previous results and was supported by up-regulated gene expression of fucosyltransferases involved in antenna fucosylation. Interestingly, hepatocyte nuclear factors (HNF)4A and HNF1A were, among others, positively associated with high CDX1 mRNA expression and have been previously proven to regulate antenna fucosylation. Besides fucosylation, we found that high CDX1 mRNA expression in cancer cell lines also associated with low levels of sialylation and galactosylation and high levels of bisection on N-glycans. Altogether, our data highlight a possible role of CDX1 in altering the N-glycosylation of colorectal cancer cells, which is a hallmark of tumor development.

scholarly journals Expression and clinical significance of PTPN12 in clear cell renal cell carcinoma

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052093604
Author(s):  
Yi Jin ◽  
Tian-xi Wang ◽  
Hao Li ◽  
Peng Guo ◽  
Qing-qing Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Relative Expression ◽  
Normal Tissues ◽  
Mrna Expression Levels

Background Clear cell renal cell carcinoma (ccRCC) is a common urological disease. Expression of the protein tyrosine phosphatase 12 gene ( PTPN12) is decreased in many cancers; however, the relationship between PTPN12 gene function and renal cancer remains unclear. Methods We detected PTPN12 protein expression in ccRCC and corresponding normal tissues from 64 patients with ccRCC by immunohistochemistry, and relative PTPN12 mRNA levels by real-time quantitative polymerase chain reaction. The relationships between the relative expression levels of PTPN12 mRNA and the patients’ clinical data were analyzed. Results PTPN12 protein and mRNA expression levels were significantly lower in ccRCC compared with the corresponding normal tissues. The mRNA expression levels in the ccRCC and corresponding normal tissues from the 64 patients with ccRCC were 0.459±0.445 and 1.001±0.128, respectively, compared with the control (glyceraldehyde 3-phosphate dehydrogenase). There was a significant correlation between relative expression of PTPN12 mRNA in ccRCC tissues and tumor diameter and clinical stage. Conclusion The expression levels of PTPN12 protein and mRNA were significantly lower in ccRCC tissues compared with normal tissues. The role of PTPN12 may provide new insights and evidence to aid the diagnosis and targeted therapy of ccRCC.

scholarly journals TRIM33 Overexpression Inhibits the Progression of Clear Cell Renal Cell Carcinoma In Vivo and In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yingkun Xu ◽  
Guangzhen Wu ◽  
Jiayao Zhang ◽  
Jianyi Li ◽  
Ningke Ruan ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mrna Expression ◽  
Wnt Signaling Pathway ◽  
Xenograft Model ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels

Purpose. To evaluate the expression of tripartite motif-containing 33 (TRIM33) in ccRCC tissues and explore the biological effect of TRIM33 on the progress of ccRCC. Method. The Cancer Genome Atlas (TCGA) database was used to examine the mRNA expression levels of TRIM33 in ccRCC tissues and its clinical relevance. Immunohistochemistry (IHC) was performed to evaluate its expression in ccRCC tissues obtained from our hospital. The correlation between TRIM33 expression and clinicopathological features of the patients was also investigated. The effects of TRIM33 on the proliferation of ccRCC cells were examined using the CCK-8 and colony formation assays. The effects of TRIM33 on the migration and invasion of ccRCC cells were explored through wound healing and transwell assays, along with the use of Wnt signaling pathway agonists in rescue experiments. Western blotting was used to explore the potential mechanism of TRIM33 in renal cancer cells. A xenograft model was used to explore the effect of TRIM33 on tumor growth. Result. Bioinformatics analysis showed that TRIM33 mRNA expression in ccRCC tissues was downregulated, and low TRIM33 expression was related to poor prognosis in ccRCC patients. In agreement with this, low TRIM33 expression was detected in human ccRCC tissues. TRIM33 expression levels were correlated with clinical characteristics, including tumor size and Furman’s grade. Furthermore, TRIM33 overexpression inhibited proliferation, migration, and invasion of 786-O and ACHN cell lines. The rescue experiment showed that the originally inhibited migration and invasion capabilities were restored. TRIM33 overexpression reduced the expression levels of β-catenin, cyclin D1, and c-myc, and inhibited tumor growth in ccRCC cells in vivo. Conclusion. TRIM33 exhibits an abnormally low expression in human ccRCC tissues. TRIM33 may serve as a potential therapeutic target and prognostic marker for ccRCC.

Decreased prolyl hydroxylase 3 mRNA expression in oncocytomas compared with clear cell renal cell carcinoma

2020 ◽  
Vol 35 (4) ◽  
pp. 80-86
Author(s):  
Spyridon Kampantais ◽  
Ilias Kounatidis ◽  
Vasiliki Kotoula ◽  
Ioannis Vakalopoulos ◽  
Konstantinos Gkagkalidis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Prolyl Hydroxylase ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Fresh Frozen

Introduction: Hypoxia inducible factors (HIF) and prolyl hydroxylase domain (PHD) enzymes play a central role in tumor progression in clear cell renal cell carcinoma (ccRCC). However, there are currently no data regarding the behavior of this pathway (HIF/PHD) in a large number of benign renal tumors, the oncocytomas. The aim of the present study was to compare the expression levels of these factors between ccRCC and oncocytoma tumors. Material and methods: A total of 56 fresh frozen specimens from patients with ccRCC and 14 oncocytoma specimens were analyzed via reverse transcription-quantitative polymerase chain reaction in order to assess the expression levels of HIF-1α, HIF-2α, PHD1, PHD2, and PHD3. The analysis involved both fresh frozen tumor samples as well as adjacent normal kidney tissues. Results: In ccRCC, HIF-1α and HIF-2α levels were upregulated in 65.5% and 71.4% of cases, respectively. PHD3 was downregulated only in 15.4% of the ccRCC cases, in contrast with oncocytoma cases, which exhibited low expression levels in the majority. The upregulation of PHD3 messenger RNA (mRNA) levels in ccRCC when compared with oncocytoma was statistically significant ( P<0.001). No other comparisons (HIF-1α, HIF-2α, PHD1, and PHD2) were significantly different. HIF-2α and PHD3 mRNA expression levels were negatively correlated with Fuhrman Grade ( P=0.029 and P=0.026, respectively) in ccRCC. Conclusion: To the best of our knowledge, this is the first time that the HIF/PHD pathway was compared between ccRCC and a common benign tumor, identifying the upregulation of PHD3 as the possible underlying factor guiding the difference in the behavior of ccRCC.

scholarly journals Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Gustavo Rodrigues Martins ◽  
Gabriela Bottaro Gelaleti ◽  
Marina Gobbe Moschetta ◽  
Larissa Bazela Maschio-Signorini ◽  
Debora Ap. Pires de Campos Zuccari
Keyword(s):  
Protein Expression ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Prognostic Markers ◽  
Tumor Development ◽  
Mammary Tumors ◽  
Clinicopathological Characteristics ◽  
Expression Levels ◽  
Gene And Protein Expression ◽  
High Gene

Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-αwith procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-αwere found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-αprotein expression and survival time was observed (p<0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p<0.05). In addition, there was a positive correlation between TNF-αand IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer.

scholarly journals Intra-tumor heterogeneity and clonal exclusivity in renal cell carcinoma

2018 ◽  
Author(s):  
Ariane L. Moore ◽  
Jack Kuipers ◽  
Jochen Singer ◽  
Elodie Burcklen ◽  
Peter Schraml ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Heterogeneity ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Evolutionary Process ◽  
Tumor Evolution ◽  
Cell Renal Cell Carcinoma ◽  
Gene Pairs

AbstractTumorigenesis is an evolutionary process in which different clones evolve over time. Interactions between clones can affect tumor evolution and hence disease progression and treatment outcome. We analyzed 178 tumor samples in 89 clear cell renal cell carcinoma patients and found high intra-tumor heterogeneity with 62% of mutations detected in only one of two biopsies per patient. We developed a novel statistical test to identify gene pairs that are altered in co-occurring clones of the same tumor, including the pairsTP53andMUC16, as well asBAP1andTP53. The mutations in these gene pairs are clonally exclusive meaning that they occurred in different branches of the tumor phylogeny, suggesting a synergistic effect between the two clones carrying these mutations. Our analysis sheds new light on tumor development and implies that clonal interactions are common within tumors, which may eventually open up novel treatment strategies to improve cancer treatment.

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