656: Comparative Expression Study of Selected Marker Genes on Paired Prostate Tissue Samples

Abstract Motivation Marker genes, defined as genes that are expressed primarily in a single cell type, can be identified from the single cell transcriptome; however, such data are not always available for the many uses of marker genes, such as deconvolution of bulk tissue. Marker genes for a cell type, however, are highly correlated in bulk data, because their expression levels depend primarily on the proportion of that cell type in the samples. Therefore, when many tissue samples are analyzed, it is possible to identify these marker genes from the correlation pattern. Results To capitalize on this pattern, we develop a new algorithm to detect marker genes by combining published information about likely marker genes with bulk transcriptome data in the form of a semi-supervised algorithm. The algorithm then exploits the correlation structure of the bulk data to refine the published marker genes by adding or removing genes from the list. Availability and implementation We implement this method as an R package markerpen, hosted on CRAN (https://CRAN.R-project.org/package=markerpen). Supplementary information Supplementary data are available at Bioinformatics online.

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Three-dimensional depth profiling of prostate tissue by micro ATR-FTIR spectroscopic imaging with variable angles of incidence

The Analyst ◽

10.1039/c8an01929k ◽

2019 ◽

Vol 144 (9) ◽

pp. 2954-2964 ◽

Cited By ~ 12

Author(s):

Cai Li Song ◽

Sergei G. Kazarian

Keyword(s):

Three Dimensional ◽

Depth Profiling ◽

Spectroscopic Imaging ◽

Prostate Tissue ◽

Tissue Samples ◽

Variable Angle ◽

Penetration Depths

Variable angle micro ATR-FTIR, via the insertion of circular apertures, was used to measure tissue samples at various penetration depths.

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Altered Autophagy in Human Adipose Tissues in Obesity

Endocrinology ◽

10.1210/endo.151.12.9995 ◽

2010 ◽

Vol 151 (12) ◽

pp. 5973-5974

Author(s):

Julia Kovsan ◽

Matthias Blüher ◽

Tanya Tarnovscki ◽

Nora Klöting ◽

Boris Kirshtein ◽

...

Keyword(s):

Adipose Tissue ◽

Metabolic Regulation ◽

Fat Distribution ◽

Multivariate Regression Analysis ◽

Marker Genes ◽

Autophagic Flux ◽

Mrna Levels ◽

Dependent Manner ◽

Tissue Samples ◽

Adipocyte Hypertrophy

Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat depot and distribution-dependent manner. Setting and Patients: Paired omental (Om) and sc adipose tissue samples were used from obese and nonobese (n = 65, cohort 1); lean, sc-obese and intraabdominally obese (n = 196, cohort 2); severely obese persons without diabetes or obesity-associated morbidity, matched for being insulin sensitive or resistant (n = 60, cohort 3). Results: Protein and mRNA levels of the autophagy genes Atg5, LC3A, and LC3B were increased in Om compared with sc, more pronounced among obese persons, particularly if with intraabdominal fat accumulation. Both adipocytes and stromal-vascular cells contribute to the expression of autophagy genes. The increased number of autophagosomes and elevated autophagic flux assessed in fat explants incubated with lysosomal inhibitors were observed in obesity, particularly in Om. The degree of visceral adiposity and adipocyte hypertrophy accounted for approximately 50% of the variance in Atg5 mRNA levels by multivariate regression analysis, whereas age, sex, measures of insulin sensitivity, inflammation, and adipose tissue stress were excluded from the model. Moreover, in cohort 3, the autophagy marker genes were increased in those who were insulin resistant compared with insulin sensitive, particularly in Om. Conclusions: Autophagy is up-regulated in adipose tissue of obese persons, especially in Om, correlating with the degree of obesity, visceral fat distribution, and adipocyte hypertrophy. This may precede the occurrence of obesity-associated morbidity.

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Epigenetic silencing of MEIS2 in prostate cancer recurrence

Clinical Epigenetics ◽

10.1186/s13148-019-0742-x ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Maibritt Nørgaard ◽

Christa Haldrup ◽

Marianne Trier Bjerre ◽

Søren Høyer ◽

Benedicte Ulhøi ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Methylation ◽

Prostate Tissue ◽

Rank Test ◽

Transcriptional Expression ◽

Tissue Samples ◽

Whitney Test ◽

Log Rank Test ◽

Mann Whitney Test ◽

Malignant Prostate

Abstract Background Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, resulting in overdiagnosis and overtreatment of clinically insignificant tumors. Thus, to improve the management of PC, novel biomarkers are urgently needed. Results In this study, we integrated genome-wide methylome (Illumina 450K DNA methylation array (450K)) and RNA sequencing (RNAseq) data performed in a discovery set of 27 PC and 15 adjacent normal (AN) prostate tissue samples to identify candidate driver genes involved in PC development and/or progression. We found significant enrichment for homeobox genes among the most aberrantly methylated and transcriptionally dysregulated genes in PC. Specifically, homeobox gene MEIS2 (Myeloid Ecotropic viral Insertion Site 2) was significantly hypermethylated (p < 0.0001, Mann-Whitney test) and transcriptionally downregulated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue in our discovery sample set, which was also confirmed in an independent validation set including > 500 PC and AN tissue samples in total (TCGA cohort analyzed by 450K and RNAseq). Furthermore, in three independent radical prostatectomy (RP) cohorts (n > 700 patients in total), low MEIS2 transcriptional expression was significantly associated with poor biochemical recurrence (BCR) free survival (p = 0.0084, 0.0001, and 0.0191, respectively; log-rank test). Next, we analyzed another RP cohort consisting of > 200 PC, AN, and benign prostatic hyperplasia (BPH) samples by quantitative methylation-specific PCR (qMSP) and found that MEIS2 was significantly hypermethylated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue samples (AN and BPH) with an AUC > 0.84. Moreover, in this cohort, aberrant MEIS2 hypermethylation was significantly associated with post-operative BCR (p = 0.0068, log-rank test), which was subsequently confirmed (p = 0.0067; log-rank test) in the independent TCGA validation cohort (497 RP patients; 450K data). Conclusions To the best of our knowledge, this is the first study to investigate, demonstrate, and independently validate a prognostic biomarker potential for MEIS2 at the transcriptional expression level and at the DNA methylation level in PC.

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Identification of cell-type-specific marker genes from co-expression patterns in tissue samples

10.1101/2020.11.07.373043 ◽

2020 ◽

Author(s):

Yixuan Qiu ◽

Jiebiao Wang ◽

Jing Lei ◽

Kathryn Roeder

Keyword(s):

Single Cell ◽

Expression Patterns ◽

R Package ◽

Marker Genes ◽

Specific Marker ◽

Cell Type ◽

Correlation Pattern ◽

Tissue Samples ◽

Bulk Data ◽

Tissue Marker

AbstractMotivationMarker genes, defined as genes that are expressed primarily in a single cell type, can be identified from the single cell transcriptome; however, such data are not always available for the many uses of marker genes, such as deconvolution of bulk tissue. Marker genes for a cell type, however, are highly correlated in bulk data, because their expression levels depend primarily on the proportion of that cell type in the samples. Therefore, when many tissue samples are analyzed, it is possible to identify these marker genes from the correlation pattern.ResultsTo capitalize on this pattern, we develop a new algorithm to detect marker genes by combining published information about likely marker genes with bulk transcriptome data in the form of a semi-supervised algorithm. The algorithm then exploits the correlation structure of the bulk data to refine the published marker genes by adding or removing genes from the list.Availability and implementationWe implement this method as an R package markerpen, hosted on https://github.com/yixuan/[email protected]

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Mutational Profiles of Marker Genes of Cervical Carcinoma in Bangladeshi patients

10.21203/rs.3.rs-39793/v1 ◽

2020 ◽

Author(s):

Shahana Sharmin ◽

Fatima Tuj Zohura ◽

Md. Sajedul Islam ◽

Anika Shimonty ◽

Md. Abdullah-Al-Kamran Khan ◽

...

Keyword(s):

Cervical Cancer ◽

Hpv Vaccination ◽

Gynecologic Cancer ◽

Treatment Modalities ◽

Nucleotide Sequence Analysis ◽

Marker Genes ◽

Cancer Tissue ◽

Cancer Type ◽

Tissue Samples ◽

Cancer Subtypes

Abstract Background: Cervical cancer is a gynecologic cancer type that develops in the cervix, accounting for 8% mortality of all female cancer patients. Infection with specific human papillomavirus (HPV) types is considered the most severe risk factor for cervical cancer. In the context of our socioeconomic conditions, an increasing burden of this disease and high mortality rate prevail in Bangladesh. Although several researches related to the epidemiology, HPV vaccination, and treatment modalities were conducted, researches on the mutation profiles of marker genes in cervical cancer in Bangladesh remain unexplored. Methods: In this study, five different genomic regions within the top three most frequently mutated genes (EGFR, KRAS and PIK3CA) in COSMIC database with a key role in the development of cervical cancers were selected to study the mutation frequency in Bangladeshi patients. In silico analysis was done in two steps: nucleotide sequence analysis and its corresponding amino acid analysis.Results: DNA from 46 cervical cancer tissue samples were extracted and amplified by PCR, using 1 set of primers designed for EGFR and 2 sets of primers designed for two different regions of both PIK3CA and KRAS gene. In total, 39 mutations were found in 28 patient samples. Eleven different mutations (23.91%), twenty-four different mutations (52.17%) and four mutations (8.7%) were found in amplified EGFR, PIK3CA and KRAS gene fragments, among which 1 (EGFR) was common in seven patient samples and 2 (PIKCA) were found in more than 1 patient. Our study shows that except for KRAS, the frequency of observed mutations in our patients is higher than those reported earlier in other parts of the world. Most of the exonic mutations were found only in the PIK3CA and EGFR genes.Conclusions: The study can be used as a basis to build a mutation database for cervical cancer in Bangladesh with the possibility of targetable oncogenic mutations. Further exploration needs to establish future diagnostics, personalized medicine decisions, and other pharmaceutical applications for specific cancer subtypes.

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The association between fecal enterotoxigenic B. fragilis with colorectal cancer

10.21203/rs.2.10895/v3 ◽

2019 ◽

Author(s):

Fakhri Haghi ◽

Elshan Goli ◽

Bahman Mirzaei ◽

Habib Zeighami

Keyword(s):

Colorectal Cancer ◽

Direct Detection ◽

Mucosal Immune Response ◽

Colorectal Disease ◽

Marker Genes ◽

Tissue Samples ◽

Potential Marker ◽

Paired Normal Tissue ◽

Stool Samples ◽

Pcr Targeting

Abstract Background Enterotoxigenic Bacteroides fragilis (ETBF) is an enterotoxin-producing bacterium that possibily has a role in the occurrence and progression of colorectal cancer (CRC) by modulating the mucosal immune response and inducing epithelial cell changes. The aim of this study was to investigate the frequency of ETBF in stool samples of CRC patients and healthy volunteers.Methods A total of 60 stool samples from confirmed CRC patients and 60 stool samples from healthy volunteers with no personal or familial history or diagnosis of colorectal disease were collected. Stool samples were screened for direct detection of B. fragilis using PCR targeting the marker genes of neu and bft. Enterotoxin isotypes bft-1, bft-2 and bft-3 were also detected in B. fragilis positive samples.Results The frequency of B. fragilis among CRC and control cases was 58.3% and 26.6%, respectively (P<0.05). The rate of bft gene in CRC cases was significantly higher than in controls (P<0.05). Also, the presence of bf t gene in CRC patients stage III was significantly higher than stages I and II (P< 0.05). Enterotoxin isotype bft-2 was detected with higher frequency among CRC patients than healthy control (P<0.05).Conclusion Our results show the association between fecal ETBF and CRC, and we suggest that detection of ETBF may be a potential marker for colorectal cancer diagnosis. However, additional investigations on tumor and paired normal tissue samples are required to substantiate this possible correlation.

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Development and Validation of a Prognostic Classifier Based on Metabolism-Related Genes for Breast Cancer

10.21203/rs.3.rs-1105292/v1 ◽

2021 ◽

Author(s):

Nan Wang ◽

Lin Li ◽

Jiangrui Chi ◽

Xinwei Liu ◽

Youyi Xiong ◽

...

Keyword(s):

Lipid Metabolism ◽

Cox Regression ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Marker Genes ◽

Tissue Samples ◽

Prognostic Gene

Abstract Background: Alterations in lipid metabolism have been implicated in the development of many tumors. However, the contribution of different lipid metabolism pathways to Breast invasive carcinoma (BRCA) remains to be fully established. Here, we attempted to ascertain the prognostic value of lipid metabolism-related genes in BRCA. Methods: We obtained RNA expression data and clinical information for BRCA and normal samples from public databases and downloaded a lipid metabolism-related gene set to harvest lipid metabolism-related genes. IPA was applied to identify the potential pathways and functions of DEGs related to lipid metabolism. Subsequently, univariate and multivariate Cox regression analyses were utilized to construct the prognostic gene signature and independent prognostic analyses. Thereafter, the differential expression of the selected marker genes SDC1 and SORBS1 in clinical tissue samples was verified by qRT-PCR, western blotting, and immunohistochemical experiments. Functional enrichment analysis of prognostic genes was achieved by the GO and KEGG databases. Moreover, Kaplan-Meier analysis, ROC curves, clinical immunohistochemistry conditions and follow-up results were employed to assess the prognostic potency. Potential compounds targeting prognostic genes were then screened by CMap database and a prognostic gene-drug interaction network was constructed using Comparative Toxicogenomics Database.Results: IPA demonstrated that the 162 lipid metabolism-related DEGs we obtained were involved in a variety of lipid metabolism and BRCA pathological signatures. Subsequent functional enrichment analysis of candidate prognostic lipid metabolism DEGs also revealed a similar outcome. The prognostic classifier we constructed comprising SDC1 and SORBS1 has a strong prognostic potency that was verified by the clinical conditions and follow-up results, it also can serve as an independent prognostic marker for BRCA. CMap filtered 37 potential compounds against prognostic genes. CTD indicated that the two prognostic genes had 16 drugs in common. Conclusion: Within this study, we identified a novel prognostic classifier based on two lipid metabolism-related genes: SDC1 and SORBS1. This classifier had accurately predicted the prognosis of our follow-up BRCA patients and this result highlighted a new perspective on the metabolic exploration of BRCA. In addition, SDC1 and SORBS1 could serve as a possible new target for the synthesis of BRCA drugs.

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Altered Autophagy in Human Adipose Tissues in Obesity

Endocrine Reviews ◽

10.1210/edrv.31.6.9998 ◽

2010 ◽

Vol 31 (6) ◽

pp. 947-947

Author(s):

Julia Kovsan ◽

Matthias Blüher ◽

Tanya Tarnovscki ◽

Nora Klöting ◽

Boris Kirshtein ◽

...

Keyword(s):

Adipose Tissue ◽

Metabolic Regulation ◽

Fat Distribution ◽

Multivariate Regression Analysis ◽

Marker Genes ◽

Autophagic Flux ◽

Mrna Levels ◽

Dependent Manner ◽

Tissue Samples ◽

Adipocyte Hypertrophy

Context Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat depot and distribution-dependent manner. Setting and Patients Paired omental (Om) and sc adipose tissue samples were used from obese and nonobese (n = 65, cohort 1); lean, sc-obese and intraabdominally obese (n = 196, cohort 2); severely obese persons without diabetes or obesity-associated morbidity, matched for being insulin sensitive or resistant (n = 60, cohort 3). Results Protein and mRNA levels of the autophagy genes Atg5, LC3A, and LC3B were increased in Om compared with sc, more pronounced among obese persons, particularly if with intraabdominal fat accumulation. Both adipocytes and stromal-vascular cells contribute to the expression of autophagy genes. The increased number of autophagosomes and elevated autophagic flux assessed in fat explants incubated with lysosomal inhibitors were observed in obesity, particularly in Om. The degree of visceral adiposity and adipocyte hypertrophy accounted for approximately 50% of the variance in Atg5 mRNA levels by multivariate regression analysis, whereas age, sex, measures of insulin sensitivity, inflammation, and adipose tissue stress were excluded from the model. Moreover, in cohort 3, the autophagy marker genes were increased in those who were insulin resistant compared with insulin sensitive, particularly in Om. Conclusions Autophagy is up-regulated in adipose tissue of obese persons, especially in Om, correlating with the degree of obesity, visceral fat distribution, and adipocyte hypertrophy. This may precede the occurrence of obesity-associated morbidity.

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