Tumors with neoadjuvant chemotherapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE52219 | GEO | 2014/02/10
SECONDARY ACCESSION(S): PRJNA227178
REPOSITORIES: GEO
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Project description:Using whole genome mRNA expression profiling of primary human tumors and unsupervised hierarchical cluster analyses, 3 novel molecular subsets (basal, luminal and p53-like subsets) of muscle-invasive bladder cancer (MIBC) were identified. 23 MVAC treated samples were used for the validation of three MIBC subsets MVAC cohort consisted of 23 FFPE pretreatment tumors (TURs) from a Phase III clinical trial were used to validate 3 molecular subsets including basal, luminal and p53-like subsets We used Illumina cDNA-mediated Annealing, Selection, Extension, and Ligation (DASL) assay that is specifically designed for the gene expression of RNA that is extracted from FFPE.
2014-02-10 | E-GEOD-52219 | biostudies-arrayexpress
Project description:Despite cisplatin-based neoadjuvant chemotherapy (NAC) 60% of patients with muscle-invasive bladder cancer still have residual invasive disease at radical cystectomy (RC). The NAC-induced biological alterations in these cisplatin-resistant tumors remain largely unstudied. We analyzed gene expression from 133 patients with residual invasive disease after cisplatin-based NAC. H&E and immunohistochemistry were used to confirm tissue sampling and gene expression analysis. Established molecular subtyping models proved to be inconsistent in their classification of the post-NAC samples. Unsupervised consensus clustering revealed four distinct consensus clusters (CC). The CC1-Basal and CC2-Luminal subtypes expressed genes consistent with a basal-like and a luminal-like phenotype, respectively. The CC3-Immune subtype had the highest immune activity, including T-cell infiltration and checkpoint molecule expression, but lacked both basal and luminal markers. The CC4-Scar-like subtype expressed genes associated with wound-healing/ scarring and was associated with favorable prognosis.
2019-01-01 | GSE124305 | GEO
Project description:Four different molecular classifications of muscle-invasive bladder cancer (MIBC) based on gene expression have been proposed. With the ultimate goal of utilizing these molecular subtypes for personalized treatment, we investigated their significance in the context of neoadjuvant cisplatin-based chemotherapy (NAC).
2017-05-25 | GSE87304 | GEO
Project description:Muscle-invasive bladder cancer (MIBC) is an aggressive disease with high morbidity and mortality that can be divided into basal and luminal subtypes based on genomic characteristics. Due to the complex heterogeneity of MIBC, specific markers are needed to distinguish MIBC subtypes to guide future clinical treatment. In this study, we explore abnormal lncrnas that are specific to the basic and intracavitary subtypes of MIBC, which will provide potential biomarkers for precision therapy of MIBC.
2023-04-14 | GSE229410 | GEO
Project description:Background: Neoadjuvant chemotherapy (NAC) is the standard treatment for muscle-invasive bladder cancer (MIBC), yet 40% of patients progress, emphasizing the need for biomarkers predictive for response or chemoresistance. Gene expression-based subtypes may serve as biomarkers, though which subtypes will respond, notably when it comes to the basal subtype, remains contentious. Patients and methods: This post hoc study analyzed 300 NAC-treated patients enrolled in the GETUG/AFU VESPER trial, with transurethral diagnostic formalin-fixed paraffin-embedded which underwent pathological review before being sequenced. ‘Mixed’ subtype was defined for tumors displaying at least two different Consensus molecular subtypes in separate regions. We evaluated the association between molecular subtypes and outcome after NAC. Tumors with remaining tissue at cystectomy (n ¼ 83) were compared with pre-treatment tumors. Results: Cases were classified basal/squamous (Ba/Sq) (n ¼ 84), luminal unstable (n = 57), stroma-rich (n = 53), mixed (n = 48), luminal papillary (n ¼ 39), luminal non-specific (n = 18), and neuroendocrine-like (n ¼ 1), with 30/48 mixed cases including a Ba/Sq component. Compared with other molecular subtypes in a multivariate Cox model, Ba/Sq (pure or mixed) patients had an increased hazard ratio (HR) of progression-free survival [HR 2.0, 95% confidence interval (CI) 1.36-3.0]. Mixed tumors were associated with decreased metabolic activity that could account for chemoresistance. Ba/Sq and mixed non-responders mostly maintained their subtype at cystectomy and have fewer myeloid dendritic cells after NAC. Tumors classified luminal papillary at transurethral resection of the urinary bladder tumor exhibited an increase in T CD4þ and macrophage signatures after NAC. Other subtypes did not show significant immune changes after NAC. Our study design relied on detailed pathological review, which precluded evaluating the mixed subtype in published datasets. Furthermore, the sample size for post-NAC analyses constrained the statistical power of these findings. Conclusions: Our findings underscore the importance of recognizing intra-tumor heterogeneity in MIBC and its role in chemoresistance associated with Ba/Sq subtype, and provide valuable insights that could help future treatment development and improve patient outcomes.
2024-10-19 | GSE279390 | GEO
Project description:Muscle invasive bladder cancer (MIBC) is a heterogeneous disease with a high recurrence rate and poor clinical outcomes. Molecular subtype provides a new framework for the study of MIBC heterogeneity. Clinically, MIBC can be classified as basal and luminal subtypes, they display different clinical and pathological characteristics, but the molecular mechanism is still unclear. Lipidomic and metabolomic molecules have recently been considered to play an important role in the genesis and development of tumors, especially as potential biomarkers. Their different expression profiles in basal and luminal subtypes provide clues for the molecular mechanism of basal and luminal subtypes and the discovery of new biomarkers. Herein, we stratified MIBC patients into basal and luminal subtype using a MIBC classifier based on transcriptome expression profiles. We qualitatively and quantitatively analyzed the lipids and metabolites of basal and luminal MIBC subtypes, and identified differential lipid and metabolite profiles of them. Our results suggest that free fatty acids (FFA) and sulfatides (SL), which are closely associated with immune and stromal cell types, can contribute to the diagnosis of basal and luminal subtypes of MIBC. Moreover, we showe that glycerophosphocholine (GCP)/imidazoles and nucleosides/imidazoles ratios can accurately distinguish the basal and luminal tumors. Overall, by integrating transcriptomic, lipidomic, and metabolomic data, our study reveals specific biomarkers to differentially diagnose basal and luminal MIBC subtypes and may provide a basis for precision therapy of MIBC.
2021-07-08 | GSE179440 | GEO
Project description:Background: Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed. Objective: To evaluate immune and stromal signatures in MIBC treated with TMT.
2019-03-23 | GSE128701 | GEO
Project description:This study aimed to identify the genetic signatures associated with disease prognosis in bladder cancer. We used 165 primary bladder cancer samples, 23 recurrent non-muscle invasive tumor tissues, 58 normal looking bladder mucosae surrounding cancer and 10 normal bladder mucosae for microarray analysis. Hierarchical clustering was used to stratify the prognosis-related gene classifiers. For validation, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of top-ranked 14 genes was performed. On unsupervised hierarchical clustering using prognosis related gene-classifier, tumors were divided into 2 groups. The high risk gene signatures had significantly poor prognosis compared to low risk gene signatures (P<0.001 by the log-rank test, respectively). The prognosis-related gene classifiers correlated significantly with recurrence of non-muscle invasive bladder cancer (hazard ratio, 4.09; 95% confidence interval [CI], 1.94 to 8.64; P<0.001), and progression (hazard ratio, 23.68; 95% confidence interval [CI], 4.91 to 114.30; P<0.001), cancer-specific survival (hazard ratio, 29.25; 95% confidence interval [CI], 3.47 to 246.98; P=0.002) and overall survival (hazard ratio, 23.33; 95% confidence interval [CI], 4.97 to 109.50; P<0.001) of muscle invasive bladder cancer (p < 0.001, respectively). No patient with non-muscle invasive bladder cancer experienced cancer progression in low risk gene signature group. Prognosis-related gene classifiers validated by RT- PCR showed identical results. Prognosis related gene-classifiers provided strong predictive value for disease outcome. These gene classifiers could assist in selecting patients who might benefit from more aggressive therapeutic intervention or surveillance. Keywords: Gene expression, Bladder cancer, Prognosis 165 primary bladder cancer samples and 23 recurrent non-muscle invasive tumor tissues from 14 patients were taken in the Chungbuk National University Hospital. Only histologically verified transitional cell carcinoma samples were selected. Simultaneously 58 normal looking bladder mucosae surrounding cancer were obtained during the operation, which were histologically confirmed normal. Also, 10 normal bladder mucosae were obtained from patients with benign disease. The normal controls were determined to be free of cancer after revealing no malignant cells on urine cytology and no observable bladder cancer on cystoscopic examination during operation for their diseases, and were histologically reconfirmed normal.
2010-05-28 | E-GEOD-13507 | biostudies-arrayexpress
Project description:Radical cystectomy with preoperative cisplatin-based neoadjuvant chemotherapy (NAC) is a current standard care for muscle-invasive bladder cancers (MIBCs). However, the response rate remains relatively low, and current clinico-pathologic and molecular classifications are inadequate to prospectively stratify MBIC patients regarding the NAC response. Here, we showed that dysregulation in glutathione (GSH) pathway is fundamental for the NAC resistance of MBICs. Comprehensive analysis of transcriptome profiles from four independent cohorts revealed that GSH metabolism and immune response genes were significantly enriched in NAC resistant and sensitive MIBC tumors, respectively. A machine learning based tumor/stroma classifier was applied for high-throughput digitalized immunohistochemistry analysis, identifying GSH dynamic proteins including glutaminase-1 (GLS1) were associated with the NAC resistance and unfavorable clinical characteristics. Consistently, GSH dynamics was activated in cisplatin resistant human MIBC cells, stimulating their proliferation, stemness features, and invasion. Combination treatment of GSH dynamics modulators and cisplatin significantly suppressed tumor growth in an orthotopic xenograft animal model. Our results demonstrate the prognostic and therapeutic values of GSH dynamic mediators in determining the clinical features and response to NAC of patients with MIBCs.
2023-08-21 | GSE212810 | GEO
Project description:Background and Objective: Neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care in muscle-invasive bladder cancer (MIBC). Pathological response has been associated with longer survival, but no currently available clinicopathological variables can identify patients likely to respond, highlighting the need for predictive biomarkers. We sought to identify a predictive signature of response to NAC integrating clinical score, taxonomic subtype, and gene expression. Material and Methods: From 1994 to 2014, pre-treatment tumor samples were collected from MIBC patients (stage T2-4N0/+M0) at two Spanish hospitals. A clinical score was determined based on stage, hydronephrosis and histology. Taxonomic subtypes (BASQ, luminal, and mixed) were identified by immunohistochemistry. A custom set of 41 genes involved in DNA damage repair and immune response was analyzed in 84 patients with the NanoString nCounter platform. Genes related to pathological response were identified by LASSO penalized logistic regression. NAC consisted of cisplatin/methotrexate/vinblastine until 2000, after which most patients received cisplatin/gemcitabine. The capacity of the integrated signature to predict pathological response was assessed with AUC. Overall survival (OS) and disease-specific survival (DSS) were analyzed with the Kaplan-Meier method. Results: LASSO selected eight genes to be included in the signature (RAD51, IFNγ, CHEK1, CXCL9, c-MET, KRT14, HERC2, FOXA1). The highest predictive accuracy was observed with the inclusion in the model of only three genes (RAD51, IFNɣ, CHEK1). The integrated clinical-taxonomic-gene expression signature including these three genes had a higher predictive ability (AUC=0.71) than only clinical score plus taxonomic subtype (AUC=0.58) or clinical score alone (AUC=0.56). This integrated signature was also significantly associated with OS (p=0.02) and DSS (p=0.02). Conclusions: We have identified a predictive signature for response to NAC in MIBC patients that integrates the expression of three genes with clinicopathological characteristics and taxonomic subtypes. Prospective studies to validate these results are ongoing.
2023-06-20 | GSE235067 | GEO