Dataset Information

Identification of New Prognostic Markers and Therapeutic Targets for Non-Muscle Invasive Bladder Cancer: HER2 as a Potential Target Antigen.

ABSTRACT: Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). However, given the current global shortage of BCG, new treatments are needed. We evaluated tumor microenvironment markers as potential BCG alternatives for NMIBC treatment. Programmed death-ligand 1, human epidermal growth factor receptor-2 (HER2), programmed cell death-1 (PD1), CD8, and Ki67 levels were measured in treatment-naïve NMIBC and MIBC patients (pTa, pT1, and pT2 stages). Univariate and multivariate Cox proportional hazard models were used to determine the impact of these markers and other clinicopathological factors on survival, recurrence, and progression. EP263, IM142, PD1, and Ki67 levels were the highest in the T2 stage, followed by the T1 and Ta stages. HER2 and IM263 expressions were higher in the T1 and T2 stages than in the Ta stage. In NMIBC, the significant prognostic factors for recurrence-free survival were adjuvant therapy, tumor grade, and HER2 positivity, whereas those for progression-free survival included age, T-stage, and IM263. Age, T-stage, EP263, PD1, CD8, and Ki67 levels were significant factors associated with overall survival. IM263 and HER2 are potential biomarkers for progression and recurrence, respectively. Therefore, we propose HER2 as a potential target antigen for intravesical therapeutics as a BCG alternative.

SUBMITTER: Chae HK

PROVIDER: S-EPMC9167936 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of New Prognostic Markers and Therapeutic Targets for Non-Muscle Invasive Bladder Cancer: HER2 as a Potential Target Antigen.

Chae Han Kyu HK Nam Wook W Kim Han Gwun HG Lim Sharon S Noh Byeong-Joo BJ Kim So Won SW Kang Gil Hyun GH Park Jong Yeon JY Eom Dae-Woon DW Kim Sung Jin SJ

Frontiers in immunology 20220523

Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). However, given the current global shortage of BCG, new treatments are needed. We evaluated tumor microenvironment markers as potential BCG alternatives for NMIBC treatment. Programmed death-ligand 1, human epidermal growth factor receptor-2 (HER2), programmed cell death-1 (PD1), CD8, and Ki67 levels were measured in treatment-naïve NMIBC and MIBC patients (pTa, pT1, and pT2 stag ...[more]

PMID: 35677058

Similar Datasets

Project description:Background/Objectives: Breast cancer remains the leading malignancy affecting women worldwide, with significant mortality rates. This study aimed to evaluate the prognostic significance of FOXM1 expression specifically in hormone receptor-positive, HER2-negative (HR+HER2-) breast cancer patients with high KPNA2 expression, and to identify potential FOXM1-targeted therapeutic strategies for this patient subgroup. Methods: We analyzed RNA sequencing and microarray data from three independent cohorts: Mackay Memorial Hospital patient samples, The Cancer Genome Atlas, and Gene Expression Omnibus databases. The expression levels of KPNA2, FOXM1, CCNB1, and CCNB2 were evaluated, with particular emphasis on stratifying patients based on KPNA2 expression levels. Their associations with clinical outcomes were assessed using Gene Set Enrichment Analysis and survival analyses. Results: While KPNA2 expression showed strong positive correlations with FOXM1, CCNB1, and CCNB2 across all datasets, our analysis revealed a distinct prognostic pattern in HR+HER2- breast cancer patients with high KPNA2 expressions. In this specific subgroup, low FOXM1 expression emerged as a favorable prognostic indicator, despite the generally poor prognosis associated with high KPNA2 levels. Gene Set Enrichment Analysis demonstrated significant enrichment of the G2/M checkpoint pathway in high KPNA2-expressing patients, suggesting potential therapeutic vulnerability to FOXM1 inhibition in this subgroup. Conclusions: This study establishes FOXM1 expression as a critical prognostic marker, specifically in KPNA2-high HR+HER2- breast cancer patients, where low FOXM1 levels correlate with improved survival outcomes. These findings suggest that FOXM1 inhibition could be particularly effective in patients with high KPNA2 expression, offering a novel therapeutic strategy for this specific molecular subtype. Several FOXM1 inhibitors, including thiostrepton and FDI-6, warrant investigation as potential targeted treatments for KPNA2-high HR+HER2- breast cancer patients.

Project description:BackgroundBladder cancer is one of the most lethal malignancy in urological system, and 20-25% of bladder cancer patients are muscle invasive with unfavorable prognosis. However, the role of alternative splicing (AS) in muscle-invasive bladder cancer (MIBC) remains to be elucidated.MethodsPercent spliced in (PSI) data obtained from the Cancer Genome Atlas (TCGA) SpliceSeq database (n = 394) were utilized to evaluate the AS events in MIBC. Prognosis-associated AS events were screened out by univariate Cox regression. LASSO Cox regression was used to identify reliable prognostic patterns in a training set and further validated in a test set. Splicing regulatory networks were constructed by correlations between PSI of AS events and RNA expression of splicing factors.ResultsAs a result, a total of 2589 prognosis-related AS events in MIBC were identified. Pathways of spliceosomal complex (FDR = 0.017), DNA-directed RNA polymerase II, core complex (FDR = 0.032), and base excision repair (FDR = 0.038) were observed to be significantly enriched. Additionally, we noticed that most of the prognosis-related AS events were favorable factors. According to the LASSO and multivariate Cox regression analyses, 15-AS-based signature was established with the area under curve (AUC) of 0.709, 0.823, and 0.857 at 1-, 3-, and 5- years, respectively. The MIBC patients were further divided into high- and low-risk groups based on median risk sores. Interestingly, we observed that the prevalence of FGFR3 with mutations and focal amplification was significantly higher in low-risk group. Functional and immune infiltration analysis suggested potential signaling pathways and distinct immune states between these two groups. Moreover, splicing correlation network displayed a regulatory mode of prognostic splicing factors (SF) in MIBC patients.ConclusionsThis study not only provided novel insights into deciphering the possible mechanism of tumorgenesis and pathogenesis but also help refine risk stratification systems and potential treatment of decision-making for MIBC.

Project description:BackgroundMuscle-invasive bladder cancer (MIBC) patients are subject to unfavorable treatment options and a high recurrence rate. The status of TP53 mutations played an essential role in the progression and the prognosis of MIBC. The present study proposed to investigate the association between TP53 mutations and immunophenotype in MIBC.ResultsWe established an immune prognostic model (IPM) ground on the immune-associated genes derived from variation analysis between wild-type TP53 and mutated TP53 TCGA-MIBC patients, and validated in another cohort from GEO database. Based on IPM, we divided MIBC patients into low and high risk subgroups. The high risk MIBC patients had higher proportions of macrophages M1, and lower proportions of T cells regulatory (Tregs) and activated dendritic cells than the low risk MIBC patients. Moreover, the expression of immune checkpoints genes (PD1, CTLA4, LAG3, HAVCR2 and TIGIT) was higher in the high risk patients than the low risk patients. In clinical application, IPM exhibited better survival prediction than conventional clinical characteristics.ConclusionsOur investigation presented practical prognostic significance for MIBC patients and displayed the overarching landscape of the immune response in the MIBC microenvironment.MethodsData were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) analysis between the TP53 mutated and wild-type MIBC patients was conducted. The CIBERSORT algorithm was performed to evaluate the proportion of immune cell types. Gene expression profiles from the TCGA and GEO were used as training and testing cohorts to build and validate an immune-related prognostic model (IPM). Genes in the IPM model were first screened by univariate Cox analysis, then filtered by the least absolute shrinkage and selection operator (LASSO) Cox regression. A nomogram was finally established and evaluated by combining both the IPM and other clinical factors.

Dataset Information

Identification of New Prognostic Markers and Therapeutic Targets for Non-Muscle Invasive Bladder Cancer: HER2 as a Potential Target Antigen.

Publications

Identification of New Prognostic Markers and Therapeutic Targets for Non-Muscle Invasive Bladder Cancer: HER2 as a Potential Target Antigen.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets