scholarly journals Transcriptome Analysis in Vulvar Squamous Cell Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6372
Author(s):  
Katharina Prieske ◽  
Malik Alawi ◽  
Anna Jaeger ◽  
Maximilian Christian Wankner ◽  
Kathrin Eylmann ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Rna Expression ◽  
Sequencing Data ◽  
Aberrant Expression ◽  
Distinct Cluster ◽  
Whole Exome Sequencing Data ◽  
Chronic Skin

To date, therapeutic strategies in vulvar squamous cell carcinoma (VSCC) are lacking molecular pathological information and targeted therapy hasn’t been approved in the treatment of VSCC, yet. Two etiological pathways are widely accepted: HPV induced vs. HPV independent, associated with chronic skin disease, often harboring TP53 mutations (mut). The aim of this analysis was to analyze the RNA expression patterns for subtype stratification on VSCC samples that can be integrated into the previously performed whole exome sequencing data for the detection of prognostic markers and potential therapeutic targets. We performed multiplex gene expression analysis (NanoString) with 770 genes in 24 prior next generation sequenced samples. An integrative data analysis was performed. Here, 98 genes were differentially expressed in TP53mut vs. HPV+ VSCC, in the TP53mut cohort, where 56 genes were upregulated and 42 were downregulated in comparison to the HPV+ tumors. Aberrant expression was primarily observed in cell cycle regulation, especially in HPV+ disease. Within the TP53mut group, a distinct cluster was identified that was correlated to a significantly worse overall survival (p = 0.017). The RNA expression profiles showed distinct patterns with regard to the known VSCC subtypes and could potentially enable further subclassification in the TP53mut groups

scholarly journals Integrative analysis of mRNA and miRNA sequencing data for gliomas of various grades

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Dmitry Y. Gvaldin ◽  
Anton A. Pushkin ◽  
Nataliya N. Timoshkina ◽  
Eduard E. Rostorguev ◽  
Arbi M. Nalgiev ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mirna Expression ◽  
Interaction Analysis ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Differential Analysis ◽  
Sequencing Data ◽  
Aberrant Expression

Abstract Background The purpose of this study was to characterize subtype-specific patterns of mRNA and miRNA expression of gliomas using The Cancer Genome Atlas (TCGA) data to search for genetic determinants that predict prognosis in terms of overall survival and to create interaction networks for grade 2 and 3 (G2 and G3) astrocytomas, oligodendrogliomas and grade 4 (G4) glioblastoma multiforme. Based on open-access TCGA data, 5 groups were formed: astrocytoma G2 (n = 58), astrocytoma G3 (n = 128), oligodendroglioma G2 (n = 102), oligodendroglioma G3 (n = 72) and glioblastoma G4 (n = 564); normal samples of brain tissue were also analysed (n = 15). Data of patient age, sex, survival and expression patterns of mRNA and miRNA were extracted for each sample. After stratification of the data into groups, a differential analysis of expression was carried out, genes and miRNAs that affect overall survival were identified and gene set enrichment analysis (GSEA) and interaction analysis were performed. Results A total of 939 samples of glial tumours were analysed, for which subtype-specific expression profiles of genes and miRNAs were identified and networks of mRNA-miRNA interactions were constructed. Genes whose aberrant expression level was associated with survival were determined, and pairwise correlations between differential gene expression (DEG) and differential miRNA expression (DE miRNA) were calculated. Conclusions The developed panel of genes and miRNAs allowed us to differentiate glioma subtypes and evaluate prognosis in terms of the overall survival of patients. The regulatory miRNA-mRNA pairs unique to the five glioma subtypes identified in this study can stimulate the development of new therapeutic approaches based on subtype-specific mechanisms of oncogenesis.

scholarly journals Identification of Biomarkers for Esophageal Squamous Cell Carcinoma Using Feature Selection and Decision Tree Methods

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chun-Wei Tung ◽  
Ming-Tsang Wu ◽  
Yu-Kuei Chen ◽  
Chun-Chieh Wu ◽  
Wei-Chung Chen ◽  
...  
Keyword(s):  
Feature Selection ◽  
Decision Tree ◽  
Squamous Cell ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Design Decision ◽  
Discrimination Ability ◽  
Normal Tissues ◽  
Tree Models

Esophageal squamous cell cancer (ESCC) is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.

scholarly journals Differential expression and correlation analysis of miRNA–mRNA profiles in swine testicular cells infected with porcine epidemic diarrhea virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoqian Zhang ◽  
Chang Li ◽  
Bingzhou Zhang ◽  
Zhonghua Li ◽  
Wei Zeng ◽  
...  
Keyword(s):  
Differential Expression ◽  
Porcine Epidemic Diarrhea Virus ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Bacterial Invasion ◽  
Sequencing Data ◽  
Diarrhea Virus ◽  
Comparison Groups ◽  
Porcine Epidemic Diarrhea

AbstractThe variant virulent porcine epidemic diarrhea virus (PEDV) strain (YN15) can cause severe porcine epidemic diarrhea (PED); however, the attenuated vaccine-like PEDV strain (YN144) can induce immunity in piglets. To investigate the differences in pathogenesis and epigenetic mechanisms between the two strains, differential expression and correlation analyses of the microRNA (miRNA) and mRNA in swine testicular (ST) cells infected with YN15, YN144, and mock were performed on three comparison groups (YN15 vs Control, YN144 vs Control, and YN15 vs YN144). The mRNA and miRNA expression profiles were obtained using next-generation sequencing (NGS), and the differentially expressed (DE) (p-value < 0.05) mRNA and miRNA were obtained using DESeq R package. mRNAs targeted by DE miRNAs were predicted using the miRanda algortithm. 8039, 8631 and 3310 DE mRNAs, and 36, 36, and 22 DE miRNAs were identified in the three comparison groups, respectively. 14,140, 15,367 and 3771 DE miRNA–mRNA (targeted by DE miRNAs) interaction pairs with negatively correlated expression patterns were identified, and interaction networks were constructed using Cytoscape. Six DE miRNAs and six DE mRNAs were randomly selected to verify the sequencing data by real-time relative quantitative reverse transcription polymerase chain reaction (qRT-PCR). Based on bioinformatics analysis, we discovered the differences were mostly involved in host immune responses and viral pathogenicity, including NF-κB signaling pathway and bacterial invasion of epithelial cells, etc. This is the first comprehensive comparison of DE miRNA–mRNA pairs in YN15 and YN144 infection in vitro, which could provide novel strategies for the prevention and control of PED.

scholarly journals Genome-wide expression profiling in colorectal cancer focusing on lncRNAs in the adenoma-carcinoma transition

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexandra Kalmár ◽  
Zsófia Brigitta Nagy ◽  
Orsolya Galamb ◽  
István Csabai ◽  
András Bodor ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Differential Expression ◽  
Colorectal Adenoma ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Aberrant Expression ◽  
Array Data ◽  
Lncrna Expression ◽  
Qrt Pcr ◽  
Mrna Targets

Abstract Background Long non-coding RNAs (lncRNAs) play a fundamental role in colorectal cancer (CRC) development, however, lncRNA expression profiles in CRC and its precancerous stages remain to be explored. We aimed to study whole genomic lncRNA expression patterns in colorectal adenoma–carcinoma transition and to analyze the underlying functional interactions of aberrantly expressed lncRNAs. Methods LncRNA expression levels of colonic biopsy samples (20 CRCs, 20 adenomas (Ad), 20 healthy controls (N)) were analyzed with Human Transcriptome Array (HTA) 2.0. Expression of a subset of candidates was verified by qRT-PCR and in situ hybridization (ISH) analyses. Furthermore, in silico validation was performed on an independent HTA 2.0, on HGU133Plus 2.0 array data and on the TCGA COAD dataset. MiRNA targets of lncRNAs were predicted with miRCODE and lncBase v2 algorithms and miRNA expression was analyzed on miRNA3.0 Array data. MiRNA-mRNA target prediction was performed using miRWALK and c-Met protein levels were analyzed by immunohistochemistry. Comprehensive lncRNA-mRNA-miRNA co-expression pattern analysis was also performed. Results Based on our HTA results, a subset of literature-based CRC-associated lncRNAs showed remarkable expression changes already in precancerous colonic lesions. In both Ad vs. normal and CRC vs. normal comparisons 16 lncRNAs, including downregulated LINC02023, MEG8, AC092834.1, and upregulated CCAT1, CASC19 were identified showing differential expression during early carcinogenesis that persisted until CRC formation (FDR-adjusted p < 0.05). The intersection of CRC vs. N and CRC vs. Ad comparisons defines lncRNAs characteristic of malignancy in colonic tumors, where significant downregulation of LINC01752 and overexpression of UCA1 and PCAT1 were found. Two candidates with the greatest increase in expression in the adenoma-carcinoma transition were further confirmed by qRT-PCR (UCA1, CCAT1) and by ISH (UCA1). In line with aberrant expression of certain lncRNAs in tumors, the expression of miRNA and mRNA targets showed systematic alterations. For example, UCA1 upregulation in CRC samples occurred in parallel with hsa-miR-1 downregulation, accompanied by c-Met target mRNA overexpression (p < 0.05). Conclusion The defined lncRNA sets may have a regulatory role in the colorectal adenoma-carcinoma transition. A subset of CRC-associated lncRNAs showed significantly differential expression in precancerous samples, raising the possibility of developing adenoma-specific markers for early detection of colonic lesions.

scholarly journals Integrated Analysis of Long Noncoding RNA and Coding RNA Expression in Esophageal Squamous Cell Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Cao ◽  
Wei Wu ◽  
Fachun Shi ◽  
Xiaobing Chen ◽  
Lihua Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Cell Cancer ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Aberrant Expression ◽  
A Genome

Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the “cancer initiatome.” Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

scholarly journals Role of miR-10b-5p in the prognosis of breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7728 ◽  
Author(s):  
Junmin Wang ◽  
Yanyun Yan ◽  
Zhiqi Zhang ◽  
Yali Li
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cancer Development ◽  
Clinicopathological Parameters ◽  
Aberrant Expression ◽  
Expression Levels ◽  
Ppi Networks

Breast cancer is the leading cause of cancer-related death in women worldwide. Aberrant expression levels of miR-10b-5p in breast cancer has been reported while the molecular mechanism of miR-10b-5p in tumorigenesis remains elusive. Therefore, this study was aimed to investigate the role of miR-10b-5p in breast cancer and the network of its target genes using bioinformatics analysis. In this study, the expression profiles and prognostic value of miR-10b-5p in breast cancer were analyzed from public databases. Association between miR-10b-5p and clinicopathological parameters were analyzed by non-parametric test. Moreover, the optimal target genes of miR-10b-5p were obtained and their expression patterns were examined using starBase and HPA database. Additionally, the role of these target genes in cancer development were explored via Cancer Hallmarks Analytics Tool (CHAT). The protein–protein interaction (PPI) networks were constructed to further investigate the interactive relationships among these genes. Furthermore, GO, KEGG pathway and Reactome pathway analyses were carried out to decipher functions of these target genes. Results demonstrated that miR-10b-5p was down-regulated in breast cancer and low expression of miR-10b-5p was significantly correlated to worse outcome. Five genes, BIRC5, E2F2, KIF2C, FOXM1, and MCM5, were considered as potential key target genes of miR-10b-5p. As expected, higher expression levels of these genes were observed in breast cancer tissues than in normal tissues. Moreover, analysis from CHAT revealed that these genes were mainly involved in sustaining proliferative signaling in cancer development. In addition, PPI networks analysis revealed strong interactions between target genes. GO, KEGG, and Reactome pathway analysis suggested that these target genes of miR-10b-5p in breast cancer were significantly involved in cell cycle. Predicted target genes were further validated by qRT-PCR analysis in human breast cancer cell line MDA-MB-231 transfected with miR-10b mimic or antisense inhibitors. Taken together, our data suggest that miR-10b-5p functions to impede breast carcinoma progression via regulation of its key target genes and hopefully serves as a potential diagnostic and prognostic marker for breast cancer.

scholarly journals BSCI-01. Small RNAseq analysis of microRNAs in brain metastasis

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii1-iii1
Author(s):  
Radim Jancalek ◽  
Frantisek Siegl ◽  
Jiri Sana ◽  
Simona Sidorova ◽  
Marek Vecera ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Expression Patterns ◽  
Predictive Biomarkers ◽  
Unknown Origin ◽  
Bioinformatic Analysis ◽  
Cdna Libraries ◽  
Sequencing Data ◽  
Aberrant Expression ◽  
Mirna Profiling ◽  
Small Rnaseq

Abstract MicroRNAs (miRNAs) are a well-known subclass of short non-coding RNAs responsible for posttranscriptional gene silencing and have been described as dysregulated in many cancers. They have also been shown to be both specific diagnostic, prognostic, and predictive biomarkers as well as therapeutic targets. Therefore, specific miRNA expression patterns of BMs of various origins could serve as a promising diagnostic tool for determining both the original tumor and the prognosis in patients with BMs of unknown origin. For identifying significantly dysregulated miRNAs among BMs (n = 90) with various origin and non-tumor brain tissues (n = 12), small RNAseq analyses were used. cDNA libraries were prepared using QIAseq miRNA Library Kit and purified by Qiaseq beads. The final sequencing analyses were performed by Next 500/550 High Output v2 Kit-75 cycles using the NextSeq 500 instrument. For miRNA mapping and analysis, Miraligner and MirBase were used. Bioinformatic analysis of obtained sequencing data identified 472 significantly dysregulated miRNAs (logFc&gt;2, adj.p-value&lt;0.05) between BM and non-tumor samples. The comparison of BMs origin from lung BMs (n = 26) with other BMs revealed 132 significantly dysregulated miRNAs, mainly miR-4662a-5p, miR-1179, miR-211-5p, miR-146a-5p, and miR-194-5p. The most significantly dysregulated miRNAs in breast BMs were miR-4728-3p, miR-211-5p, miR-184, miR-365b-5p, and miR-2115-3p. In BMs originating from melanoma, miR-200c-3p, miR-141-5p, miR-200b-5p, miR-514a-3p, and miR-200b-3p showed the most aberrant expression. We have demonstrated that miRNA profiling could be a potent tool for the partition of brain metastases based on their origin. We found that miRNA signatures corresponding to particular origins are rather distinct from the profiles of the rest of BMs. Our results suggest that after validation, miRNA profiling can be used to identify the origin of brain metastases and potentially for the refinement of the diagnosis. Supported by the Ministry of Health of the Czech Republic, grant nr. NV18-03-00398.

scholarly journals Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lin Wang ◽  
Yi Zhang ◽  
Kuokuo Li ◽  
Zheng Wang ◽  
Xiaomeng Wang ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
De Novo ◽  
Expression Patterns ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Sequencing Data ◽  
Bioinformatics Pipeline ◽  
Functional Relationships ◽  
Whole Exome Sequencing Data

Abstract Background Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). Methods We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. Results Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p = 0.038) and X-linked inherited PTVs in males (p = 0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. Limitations The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. Conclusions ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs.

scholarly journals The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1031
Author(s):  
Sotirios G. Doukas ◽  
Dimitra P. Vageli ◽  
George Lazopoulos ◽  
Demetrios A. Spandidos ◽  
Clarence T. Sasaki ◽  
...  
Keyword(s):  
Dna Repair ◽  
Head And Neck ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tobacco Smoking ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Cell Progression ◽  
Squamous Cancer

Tobacco smoking is a common risk factor for lung cancer and head and neck cancer. Molecular changes such as deregulation of miRNA expression have been linked to tobacco smoking in both types of cancer. Dysfunction of the Mismatch DNA repair (MMR) mechanism has also been associated with a poor prognosis of these cancers, while a cross-talk between specific miRNAs and MMR genes has been previously proposed. We hypothesized that exposure of lung and head and neck squamous cancer cells (NCI and FaDu, respectively) to tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is capable of altering the expression of MSH2 and MLH1, key MMR components, by promoting specific miRNA deregulation. We found that either a low (1 μM) or high (2 μM) dose of NNK induced significant upregulation of “oncomirs” miR-21 and miR-155 and downregulation of “tumor suppressor” miR-422a, as well as the reduction of MMR protein and mRNA expression, in NCI and FaDu, compared to controls. Inhibition of miR-21 restored the NNK-induced reduced MSH2 phenotype in both NCI and FaDu, indicating that miR-21 might contribute to MSH2 regulation. Finally, NNK exposure increased NCI and FaDu survival, promoting cancer cell progression. We provide novel findings that deregulated miR-21, miR-155, and miR-422a and MMR gene expression patterns may be valuable biomarkers for lung and head and neck squamous cell cancer progression in smokers.

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