Association of RERG Expression with Female Survival Advantage in Malignant Pleural Mesothelioma

Rienzo, Assunta De; Coleman, Melissa H.; Yeap, Beow Y.; Severson, David T.; Wadowski, Benjamin; Gustafson, Corinne E.; Jensen, Roderick V.; Chirieac, Lucian R.; Richards, William G.; Bueno, Raphael

doi:10.3390/cancers13030565

Cited by 4 publications

(6 citation statements)

References 41 publications

(20 reference statements)

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“…In contrast, high RERG conferred no prognostic benefit for mesothelioma in males. 49 Our previous research shows the sex survival difference decreases in older cohorts when stratified by age, somehow supporting this hypothesis.…”

Section: Discussionsupporting

confidence: 58%

Malignant pleural mesothelioma characteristics and outcomes: A SEER‐Medicare analysis

Taioli

Wolf

Alpert

et al. 2023

Journal of Surgical Oncology

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Background: Pleural mesothelioma is rare cancer linked to asbestos exposure.Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.Materials and Methods: Malignant pleural mesothelioma cases diagnosed from 1992 to 2015 were queried from the linked SEER-Medicare database. Multivariable logistic regression was used to assess the clinical and demographic factors associated with sex. A multivariable Cox proportional hazards model and propensity matching methods were used to assess sex differences in overall survival (OS) while accounting for potential confounders.Results: Among 4201 patients included in the analysis, 3340 (79.5%) were males and 861 (20.5%) females. Females were significantly older, with more epithelial histology than males were, and had significantly better OS, adjusted for confounders (adjusted hazard ratio, 0.83, 95% confidence interval: 0.76-0.90). Other variables independently associated with improved survival included younger age at diagnosis, having a spouse/domestic partner, epithelial histology, lower comorbidity score, and receipt of surgery or chemotherapy. Conclusions:The study describes sex differences in mesothelioma occurrence, treatment, and survival and is the first to examine SEER-Medicare. It provides directions for future research into potential therapeutic targets.

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Section: Discussionsupporting

confidence: 58%

Malignant pleural mesothelioma characteristics and outcomes: A SEER‐Medicare analysis

Taioli

Wolf

Alpert

et al. 2023

Journal of Surgical Oncology

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“…We enrolled the gene expression profiles and clinical information of MPM datasets from Gene Expression Omnibus (GEO) with the accession numbers GSE29354 ( 16 ), GSE2549 ( 17 ), GSE163722 ( 18 ), and GSE51024 ( 19 ). The expression files of the MTAB-6877 dataset ( 20 ) were provided in ArrayExpress ( ).…”

Section: Methodsmentioning

confidence: 99%

Unraveling tumor microenvironment heterogeneity in malignant pleural mesothelioma identifies biologically distinct immune subtypes enabling prognosis determination

Yang

et al. 2022

Front. Oncol.

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BackgroundMalignant pleural mesothelioma (MPM) is a rare and intractable disease exhibiting a remarkable intratumoral heterogeneity and dismal prognosis. Although immunotherapy has reshaped the therapeutic strategies for MPM, patients react with discrepant responsiveness.MethodsHerein, we recruited 333 MPM patients from 5 various cohorts and developed an in-silico classification system using unsupervised Non-negative Matrix Factorization and Nearest Template Prediction algorithms. The genomic alterations, immune signatures, and patient outcomes were systemically analyzed across the external TCGA-MESO samples. Machine learning-based integrated methodology was applied to identify a gene classifier for clinical application.ResultsThe gene expression profiling-based classification algorithm identified immune-related subtypes for MPMs. In comparison with the non-immune subtype, we validated the existence of abundant immunocytes in the immune subtype. Immune-suppressed MPMs were enriched with stroma fraction, myeloid components, and immunosuppressive tumor-associated macrophages (TAMs) as well exhibited increased TGF-β signature that informs worse clinical outcomes and reduced efficacy of anti-PD-1 treatment. The immune-activated MPMs harbored the highest lymphocyte infiltration, growing TCR and BCR diversity, and presented the pan-cancer immune phenotype of IFN-γ dominant, which confers these tumors with better drug response when undergoing immune checkpoint inhibitor (ICI) treatment. Genetically, BAP1 mutation was most commonly found in patients of immune-activated MPMs and was associated with a favorable outcome in a subtype-specific pattern. Finally, a robust 12-gene classifier was generated to classify MPMs with high accuracy, holding promise value in predicting patient survival.ConclusionsWe demonstrate that the novel classification system can be exploited to guide the identification of diverse immune subtypes, providing critical biological insights into the mechanisms driving tumor heterogeneity and responsible for cancer-related patient prognoses.

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“…The mRNA expression profile datasets of GSE48855 12 and GSE51636 17 were retrieved from the GEO database ( http://www.ncbi.nlm.nih.gov/geo/ ) using “carbon nanotubes” AND “mesothelioma” as the keywords, while GSE51024, 19 GSE2549 20 and GSE42977 21 , 22 microarray datasets were selected from the GEO database because they compared the gene expression profiles between MPM and normal specimens. In the GSE48855 dataset, there were, respectively, three human immortalized pleural mesothelial cells (MeT5A) exposed to subcytotoxic concentration (0.02 μg/cm 2 ) of SWCNTs, MWCNTs or crocidolite asbestos for up to 4 months to induce malignant transformation; Survanta ® dispersant (n = 3) or saline (n = 3) was set as the control for CNT or asbestos, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Fifty-five frozen resected MPM tissues and 41 paired normal lung parenchyma tissues were used for the gene expression profiling study in the GSE51024 dataset (platform: [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array, GPL570); 19 40 MPM surgical specimens, 5 normal pleura and 5 normal lung specimens, 5 MPM cell lines and 1 non-tumorigenic mesothelial cellline MeT5A were included in the GSE2549 dataset (platform: [HG-U133A] Affymetrix Human Genome U133A Array, GPL96); 20 39 MPM specimens (histological subtype: n = 24 as epithelioid; n = 8 as sarcomatoid; n = 7 as biphasic), 7 normal pleura and 2 normal lung specimens were contained in the GSE42977 dataset (platform: Illumina HumanRef-6 v2.0 expression beadchip, GPL6790). 21,22 MPM was believed to arise from mesothelial cells in the pleura and frequently envelopes lung tissues. Thus, both pleura and lung tissues were included as controls.…”

Section: Data Sourcementioning

confidence: 99%

“…The expression levels of genes in crucial modules extracted from the GSE48855 dataset were further validated in the mRNA expression profile (GSE51636) of mice exposed to CNTs or not. 17 Furthermore, the expression, predictive and prognostic abilities of hub genes in MPM samples were also explored using the datasets (GSE51024, 19 GSE2549 20 and GSE42977 21 , 22 ) from the Gene Expression Omnibus (GEO) database and several online tools based on The Cancer Genome Atlas (TCGA) dataset. The functions of hub genes were predicted by linking to the infiltration levels of various immune cells since inflammation seemed to be an important contributor for CNT-associated MPM.…”

Section: Introductionmentioning

confidence: 99%

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Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

Xie

et al. 2021

IJGM

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Background Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM. Methods Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein–protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers. Results WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of >0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1). Conclusion These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.

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Association of RERG Expression with Female Survival Advantage in Malignant Pleural Mesothelioma

Cited by 4 publications

References 41 publications

Malignant pleural mesothelioma characteristics and outcomes: A SEER‐Medicare analysis

Malignant pleural mesothelioma characteristics and outcomes: A SEER‐Medicare analysis

Unraveling tumor microenvironment heterogeneity in malignant pleural mesothelioma identifies biologically distinct immune subtypes enabling prognosis determination

Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

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