Gene set based systematic analysis of prostate cancer and its subtypes

2020 ◽  
Vol 16 (2) ◽  
pp. 4381-4393
Author(s):  
Senlin Ye ◽  
Haohui Wang ◽  
Kancheng He ◽  
Hongwei Shen ◽  
Mou Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Expression Patterns ◽  
Methylation Status ◽  
Gene Expression Patterns ◽  
Biological Functions ◽  
Systematic Analysis ◽  
Gene Set ◽  
Analysis Strategy ◽  
Similarities And Differences

Aim: A gene set based systematic analysis strategy is used to investigate prostate tumors and its subclusters with focuses on similarities and differences of biological functions. Results: Dysregulation of methylation status, as well as RAS/RAF/ERK and PI3K-ATK signaling pathways, were found to be the most dramatic changes during prostate cancer tumorigenesis. Besides, neural and inflammation microenvironment is also significantly divergent between tumor and adjacent tissues. Insights of subclasses within prostate tumor cohorts revealed four different clusters with distinct gene expression patterns. We found that samples are mainly clustered by immune environments and proliferation traits. Conclusion: The findings of this article may help to advance the progress of identifying better diagnosis biomarkers and therapeutic targets.

scholarly journals Oral Vitamin D supplementation induces transcriptomic changes in rectal mucosa that are consistent with anti-tumour effects.

2021 ◽  
Author(s):  
Peter G Vaughan-Shaw ◽  
Graeme Grimes ◽  
James P Blackmur ◽  
Maria Timofeeva ◽  
Marion Walker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Expression Patterns ◽  
Rectal Mucosa ◽  
Vitamin D Supplementation ◽  
Gene Expression Patterns ◽  
Blood Biomarkers ◽  
Oral Vitamin ◽  
Gene Set ◽  
Transcriptomic Changes

Background Risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in-vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. Methods Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). Results 629 genes were associated with 25-OHD level (P<0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P<1.0E-07; downregulated gene-set P<2.6E-05) and corresponding GO terms (P=2.90E-02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P<0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI:0.66-1.00]), and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI:0.77-0.89]; PPP1CC AUC=0.91 [95%CI:0.86-0.95]). Conclusions Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumor transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.

Prediction of metastatic behavior in high-grade pleomorphic soft tissue sarcomas by gene expression.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10561-10561
Author(s):  
Keith M. Skubitz ◽  
Amy Skubitz ◽  
Wayne Xu ◽  
Xianghua Luo ◽  
Pauline Lagarde ◽  
...  
Keyword(s):  
Gene Expression ◽  
Soft Tissue ◽  
Expression Patterns ◽  
Soft Tissue Sarcomas ◽  
Gene Expression Patterns ◽  
High Grade ◽  
Data Set ◽  
Gene Set ◽  
Kaplan Meier ◽  
Gene Sets

10561 Background: The biologic heterogeneity of soft tissue sarcomas (STS) complicates treatment. Metastatic propensity may be determined by gene expression patterns that do not correlate well with morphology. In earlier studies, gene expression patterns were identified that distinguish 2 subsets of clear cell renal carcinoma (RCC), serous ovarian carcinoma (OVCA), and aggressive fibromatosis (AF). We reported the use of a gene set derived from these three studies to separate 73 high grade STS into groups with different probabilities of developing metastatic disease (PrMet). We wished to confirm our findings using an independent data set. Methods: We utilized these gene sets, hierarchical clustering (HC), Kaplan-Meier, and log-rank analyses to examine the Affymetrix HU_133 expression profiles of 309 STS. Results: HC using a pooled gene set derived from the AF-, RCC-, and OVCA-gene sets identified subsets of the STS samples. Kaplan-Meier analysis revealed differences in PrMet between the clusters defined by the first branch point of the clustering dendrogram (p=0.048), and also among the 4 different clusters defined by the second branch points (p<0.0001). Analysis also revealed differences in PrMet between the leiomyosarcomas (LMS), dedifferentiated liposarcomas (LipoD), and undifferentiated pleomorphic sarcomas (UDS) (p=0.0004). HC of the LipoD and UDS samples with the pooled probe set divided the samples into 2 groups with different PrMet (p=0.013, and 0.0002, respectively). HC of the UDS samples also showed 4 groups with different PrMet (p=0.0007). In contrast, HC found no subgroups of the LMS samples. Each individual gene set (AF-, RCC-, and OVCA-) separated the UDS samples into subsets of different metastatic outcome, but only the AF- gene set separated the LipoD samples, and no gene set identified LMS subsets. Conclusions: These data confirm our earlier studies and suggest that this approach may allow the identification of more than 2 subsets of high grade STS, each with distinct clinical behavior, and may be useful to stratify STS in clinical trials and in patient management.

scholarly journals Comprehensive and Systematic Analysis of Gene Expression Patterns Associated with Body Mass Index

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Paule V. Joseph ◽  
Rosario B. Jaime-Lara ◽  
Yupeng Wang ◽  
Lichen Xiang ◽  
Wendy A. Henderson
Keyword(s):  
Gene Expression ◽  
Body Mass Index ◽  
Body Mass ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Systematic Analysis

Gene Set Enrichment Analyses Revealed Differences in Gene Expression Patterns between Males and Females

2009 ◽  
Vol 9 (3) ◽  
pp. 55-63 ◽  
Author(s):  
Wei Zhang ◽  
R. Stephanie Huang ◽  
Shiwei Duan ◽  
M. Eileen Dolan
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Males And Females

scholarly journals Oral vitamin D supplementation induces transcriptomic changes in rectal mucosa that are linked to anti-tumour effects

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
P. G. Vaughan-Shaw ◽  
G. Grimes ◽  
J. P. Blackmur ◽  
M. Timofeeva ◽  
M. Walker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Expression Patterns ◽  
Rectal Mucosa ◽  
Vitamin D Supplementation ◽  
Gene Expression Patterns ◽  
Blood Biomarkers ◽  
Oral Vitamin ◽  
Gene Set ◽  
Transcriptomic Changes

Abstract Background The risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. Methods Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). Results Six hundred twenty-nine genes were associated with 25-OHD level (P < 0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P < 1.0E−07; downregulated gene-set P < 2.6E−05) and corresponding GO terms (P = 2.90E−02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P < 0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI 0.66–1.00]) and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI 0.77–0.89]; PPP1CC AUC=0.91 [95%CI 0.86–0.95]). Conclusions Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects, and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumour transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.

Gene expression patterns in blood predict future severe endpoints in community acquired pneumonia

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S8-S9
Author(s):  
M Bauer ◽  
H Kirsten ◽  
E Grunow ◽  
P Ahnert ◽  
M Kiehntopf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Community Acquired Pneumonia ◽  
Gene Expression Patterns
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