scholarly journals Comparative Analysis on Molecular Characteristics of Chromophobe Renal Cancer and Oncocytoma

Author(s):  
Khaled bin Satter ◽  
Paul Minh Huy Tran ◽  
Lynn Kim Hoang Tran ◽  
Shan Bai ◽  
Natasha M. Savage ◽  
...  

Chromophobe renal cell carcinoma (chRCC) and oncocytoma (RO) are renal tumor types originating from alpha intercalated cells of the collecting ducts of the kidney. Both tumor types have similar gross histological morphology and increased mitochondria, which leads to difficulties differentiating between these tumors, especially with core biopsy samples. This study aims to apply a machine learning approach to develop a molecular classifier based on transcriptomics data. Here we generated a meta-data set containing 62 chRCC and 45 RO gene expression arrays. Arrays were subjected to quality control steps, and genes were selected based on differential expression and ROC analysis. The final gene list was evaluated with UMAP based dimension reduction followed by density-based clustering with 95.5% accuracy. Molecular profiling by KEGG pathway analysis identified enrichment of fatty acid oxidation pathway in RO. We finally identified and validated the 30-gene signature, with an accuracy of 94.4% to distinguish chRCC from RO on UMAP analysis. Our results show that chRCC and RO have a distinct gene signature that can differentiate these tumors and complement histology for routine diagnosis of these two tumors.

1998 ◽  
Vol 95 (16) ◽  
pp. 9407-9412 ◽  
Author(s):  
Wojciech Makałowski ◽  
Mark S. Boguski

We have rigorously defined 2,820 orthologous mRNA and protein sequence pairs from rats, mice, and humans. Evolutionary rate analyses indicate that mammalian genes are evolving 17–30% more slowly than previous textbook values. Data are presented on the average properties of mRNA and protein sequences, on variations in sequence conservation in coding and noncoding regions, and on the absolute and relative frequencies of repetitive elements and splice sites in untranslated regions of mRNAs. Our data set contains 1,880 unique human/rodent sequence pairs that represent about 2–4% of all mammalian genes. Of the 1,880 human orthologs, 70% are present on a new gene map of the human genome, thus providing a valuable resource for cross-referencing human and rodent genomes. In addition to comparative mapping, these results have practical applications in the interpretation of noncoding sequence conservation between syntenic regions of human and mouse genomic sequence, and in the design and calibration of gene expression arrays.


Author(s):  
Lianbo Yu ◽  
Parul Gulati ◽  
Soledad Fernandez ◽  
Michael Pennell ◽  
Lawrence Kirschner ◽  
...  

Gene expression microarray experiments with few replications lead to great variability in estimates of gene variances. Several Bayesian methods have been developed to reduce this variability and to increase power. Thus far, moderated t methods assumed a constant coefficient of variation (CV) for the gene variances. We provide evidence against this assumption, and extend the method by allowing the CV to vary with gene expression. Our CV varying method, which we refer to as the fully moderated t-statistic, was compared to three other methods (ordinary t, and two moderated t predecessors). A simulation study and a familiar spike-in data set were used to assess the performance of the testing methods. The results showed that our CV varying method had higher power than the other three methods, identified a greater number of true positives in spike-in data, fit simulated data under varying assumptions very well, and in a real data set better identified higher expressing genes that were consistent with functional pathways associated with the experiments.


2021 ◽  
Vol 22 (6) ◽  
pp. 3162
Author(s):  
Erni Sulistiyani ◽  
James M. Brimson ◽  
Ajjima Chansaenroj ◽  
Ladawan Sariya ◽  
Ganokon Urkasemsin ◽  
...  

Antioxidant agents are promising pharmaceuticals to prevent salivary gland (SG) epithelial injury from radiotherapy and their associated irreversible dry mouth symptoms. Epigallocatechin-3-gallate (EGCG) is a well-known antioxidant that can exert growth or inhibitory biological effects in normal or pathological tissues leading to disease prevention. The effects of EGCG in the various SG epithelial compartments are poorly understood during homeostasis and upon radiation (IR) injury. This study aims to: (1) determine whether EGCG can support epithelial proliferation during homeostasis; and (2) investigate what epithelial cells are protected by EGCG from IR injury. Ex vivo mouse SG were treated with EGCG from 7.5–30 µg/mL for up to 72 h. Next, SG epithelial branching morphogenesis was evaluated by bright-field microscopy, immunofluorescence, and gene expression arrays. To establish IR injury models, linear accelerator (LINAC) technologies were utilized, and radiation doses optimized. EGCG epithelial effects in these injury models were assessed using light, confocal and electron microscopy, the Griess assay, immunohistochemistry, and gene arrays. SG pretreated with EGCG 7.5 µg/mL promoted epithelial proliferation and the development of pro-acinar buds and ducts in regular homeostasis. Furthermore, EGCG increased the populations of epithelial progenitors in buds and ducts and pro-acinar cells, most probably due to its observed antioxidant activity after IR injury, which prevented epithelial apoptosis. Future studies will assess the potential for nanocarriers to increase the oral bioavailability of EGCG.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhixiang Yu ◽  
Haiyan He ◽  
Yanan Chen ◽  
Qiuhe Ji ◽  
Min Sun

AbstractOvarian cancer (OV) is a common type of carcinoma in females. Many studies have reported that ferroptosis is associated with the prognosis of OV patients. However, the mechanism by which this occurs is not well understood. We utilized Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) to identify ferroptosis-related genes in OV. In the present study, we applied Cox regression analysis to select hub genes and used the least absolute shrinkage and selection operator to construct a prognosis prediction model with mRNA expression profiles and clinical data from TCGA. A series of analyses for this signature was performed in TCGA. We then verified the identified signature using International Cancer Genome Consortium (ICGC) data. After a series of analyses, we identified six hub genes (DNAJB6, RB1, VIMP/ SELENOS, STEAP3, BACH1, and ALOX12) that were then used to construct a model using a training data set. The model was then tested using a validation data set and was found to have high sensitivity and specificity. The identified ferroptosis-related hub genes might play a critical role in the mechanism of OV development. The gene signature we identified may be useful for future clinical applications.


2018 ◽  
Vol 7 (18) ◽  
Author(s):  
Matthew Chung ◽  
Laura Teigen ◽  
Silvia Libro ◽  
Robin E. Bromley ◽  
Nikhil Kumar ◽  
...  

Here, we present a comprehensive transcriptomics data set of Brugia malayi, its Wolbachia endosymbiont wBm, and its vector host. This study samples from 16 stages across the entire B. malayi life cycle, including stage 1 through 4 larvae, adult males and females, embryos, immature microfilariae, and mature microfilariae.


2015 ◽  
Vol 23 (3) ◽  
pp. 617-626 ◽  
Author(s):  
Nophar Geifman ◽  
Sanchita Bhattacharya ◽  
Atul J Butte

Abstract Objective Cytokines play a central role in both health and disease, modulating immune responses and acting as diagnostic markers and therapeutic targets. This work takes a systems-level approach for integration and examination of immune patterns, such as cytokine gene expression with information from biomedical literature, and applies it in the context of disease, with the objective of identifying potentially useful relationships and areas for future research. Results We present herein the integration and analysis of immune-related knowledge, namely, information derived from biomedical literature and gene expression arrays. Cytokine-disease associations were captured from over 2.4 million PubMed records, in the form of Medical Subject Headings descriptor co-occurrences, as well as from gene expression arrays. Clustering of cytokine-disease co-occurrences from biomedical literature is shown to reflect current medical knowledge as well as potentially novel relationships between diseases. A correlation analysis of cytokine gene expression in a variety of diseases revealed compelling relationships. Finally, a novel analysis comparing cytokine gene expression in different diseases to parallel associations captured from the biomedical literature was used to examine which associations are interesting for further investigation. Discussion We demonstrate the usefulness of capturing Medical Subject Headings descriptor co-occurrences from biomedical publications in the generation of valid and potentially useful hypotheses. Furthermore, integrating and comparing descriptor co-occurrences with gene expression data was shown to be useful in detecting new, potentially fruitful, and unaddressed areas of research. Conclusion Using integrated large-scale data captured from the scientific literature and experimental data, a better understanding of the immune mechanisms underlying disease can be achieved and applied to research.


Author(s):  
William C Dungan ◽  
Michael R Garrett ◽  
Bradley A. Welch ◽  
William J Lawson ◽  
Alexandra R Himel ◽  
...  

Background. Vertical sleeve gastrectomy (VSG) is a surgical weight loss procedure that resects 80% of the stomach, creating a tube linking the esophagus to the duodenum. Because of the efficacy and relative simplicity of VSG, it is preferred in the U.S with VSG currently at >61% of bariatric surgeries performed. Surprisingly, there has never been a complete molecular characterization of the human stomach fundus and corpus. Here we compare and contrast the molecular make-up of these regions. Methods. We performed a prospective study to obtain gastric tissue samples from patients undergoing VSG. Paired fundus and corpus samples were obtained Whole genome transcriptome analysis was performed by RNA sequencing, with key findings validated by qPCR. Results. Participants were primarily female (95.8%) and white (79.15%). Mean BMI, body weight, and age were 46.1 kg/m2, 121.6 kg, and 43.29 years, respectively. Overall, 432 gene transcripts were significantly different between the fundus and corpus (p<0.05). A significant correlation was found between the RNAseq data set and qPCR validation, demonstrating robust gene expression differences. Significant genes included: progastricsin, acid chitinase, gastokine 1 and 2 in both fundus and corpus. Of the very highly expressed genes in both regions, 87% were present in both the stomach's fundus and corpus, indicating substantial overlap. Conclusions. Despite significant overlap in the greater curvature gene signature, regional differences exist. Given that the mechanism of VSG is partly unresolved, the potential that the resected tissue may express genes that influence long-term body weight regulation is unknown and could influence VSG outcomes.


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