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Association of RERG Expression to Female Survival Advantage in Malignant Pleural Mesothelioma II

ABSTRACT: Sex differences in incidence, prognosis, and treatment response have been described for many cancers. In malignant pleural mesothelioma (MPM), a lethal disease associated with asbestos exposure, men outnumber women 4 to 1, but women consistently live longer than men following surgery-based therapy. This study investigated whether tumor expression of genes associated with estrogen signaling could potentially explain observed survival differences. Two microarray datasets of MPM tumors were analyzed to discover estrogen-related genes associated with survival. A validation cohort of MPM tumors was selected to balance the numbers of men and women and control for competing prognostic influences. The RAS like estrogen regulated growth inhibitor (RERG) gene was identified as the most differentially-expressed estrogen-related gene in these tumors and predicted prognosis in discovery datasets. In the sex-matched validation cohort, low RERG expression was significantly associated with increased risk of death among women. No association between RERG expression and survival was found among men, and no relationship between estrogen receptor protein or gene expression and survival was found for either sex. Additional investigations are needed to elucidate the molecular mechanisms underlying this association and its sex specificity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE163721 | GEO | 2021/02/15

REPOSITORIES: GEO

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Association of RERG Expression to Female Survival Advantage in Malignant Pleural Mesothelioma I

Project description:Sex differences in incidence, prognosis, and treatment response have been described for many cancers. In malignant pleural mesothelioma (MPM), a lethal disease associated with asbestos exposure, men outnumber women 4 to 1, but women consistently live longer than men following surgery-based therapy. This study investigated whether tumor expression of genes associated with estrogen signaling could potentially explain observed survival differences. Two microarray datasets of MPM tumors were analyzed to discover estrogen-related genes associated with survival. A validation cohort of MPM tumors was selected to balance the numbers of men and women and control for competing prognostic influences. The RAS like estrogen regulated growth inhibitor (RERG) gene was identified as the most differentially-expressed estrogen-related gene in these tumors and predicted prognosis in discovery datasets. In the sex-matched validation cohort, low RERG expression was significantly associated with increased risk of death among women. No association between RERG expression and survival was found among men, and no relationship between estrogen receptor protein or gene expression and survival was found for either sex. Additional investigations are needed to elucidate the molecular mechanisms underlying this association and its sex specificity.

2021-02-15 | GSE163720 | GEO

Single-Cell Profiling of Murine Bladder Cancer Identifies Sex Specific Transcriptional Signatures with Prognostic Relevance

Project description:Bladder cancer (BLCA) is more common in men but more aggressive in women. A common model used to study sex-based differences in cancer biology is murine BLCA generated by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). While tumors in this model have been profiled, these profiles provided limited information on the tumor microenvironment. Hence, we applied single-cell RNA sequencing to characterize cell type specific transcriptional differences between male and female BBN induced tumors and then studied their human relevance. We found proportion and gene expression differences in the epithelial and non-epithelial subpopulations between male and female tumors. Of translational importance, expression of several genes was found to predict sex specific survival in several human BLCA datasets. We also noted a male biased CD8 T cell exhaustion program in this model that correlates highly with androgen receptor activity. Our study identified novel and clinically relevant sex specific transcriptional signatures and validates the relevance of the BBN model for studying sex differences in human BLCA. This work highlights the importance of considering sex as a biological variable in cancer marker development.

2023-08-09 | GSE229168 | GEO

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2007-11-24 | GSE9676 | GEO

Project description:we aimed to explore the molecular importance of the estrogen pathway through a detailed analysis of the transcriptomic profile of lactotroph tumors from 20 men and 10 women. We undertook gene expression analysis of the 30 selected lactotroph tumors following their pathological grading using the five-tiered classification.

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The Effect of Steroid and ERa agonism on Th2 cells

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2008-06-17 | E-GEOD-9676 | biostudies-arrayexpress

The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene

Project description:Men with melanoma have a significantly worse prognosis than women, and the biological underpinnings of this difference are unknown. The current study demonstrates that loss of the inactivated X chromosome in melanomas arising in females is strongly associated with poor distant metastasis free survival. High expression of the gonosomal PPP2R3B gene, a gene that escapes inactivation, is independently correlated with survival. PPP2R3B downregulates melanoma growth by negatively interfering with DNA replication and cell cycle progression through its role in stabilizing CDC6/CDT1 interaction during the replication origins firing and as such behaves functionally as a tumor suppressor gene. Fourty-nine fresh frozen primary melanoma samples were profiled by CGH array using sex-matched commercial DNA as reference.

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Long noncoding RNAs are dysregulated in malignant pleural mesothelioma

Project description:Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers, and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

2013-08-22 | GSE48174 | GEO

Sex and aging effect on skeletal muscle transcriptome in humans

Project description:The aim of this investigation was to develop a global view of muscle transcriptional differences between older men and women and with aging for each sex.

2013-02-28 | GSE38718 | GEO

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