scholarly journals Integrative multi-omics analysis of muscle-invasive bladder cancer identifies prognostic biomarkers for frontline chemotherapy and immunotherapy

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Qianxing Mo ◽  
Roger Li ◽  
Dennis O. Adeegbe ◽  
Guang Peng ◽  
Keith Syson Chan
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Clustering Analysis ◽  
Prognostic Value ◽  
Invasive Bladder Cancer ◽  
Expression Data ◽  
Muscle Invasive Bladder Cancer ◽  
Lower Response Rate ◽  
Muscle Invasive

AbstractOnly a subgroup of patients with muscle-invasive bladder cancer (MIBC) are responders toward cisplatin-based chemotherapy and PD-L1 blockade immunotherapy. There is a clinical need to identify MIBC molecular subtypes and biomarkers for patient stratification toward the therapies. Here, we performed an integrative clustering analysis of 388 MIBC samples with multi-omics data and identified basal and luminal/differentiated integrative subtypes and derived a 42 gene panel for classification of MIBC. Using nine additional gene expression data (n = 844), we demonstrated the prognostic value of the 42 basal-luminal genes. The basal subtype was associated with worse overall survival in patients receiving no neoadjuvant chemotherapy (NAC), but better overall survival in patients receiving NAC in two clinical trials. Each of the subtypes could be further divided into chr9 p21.3 normal or loss subgroup. The patients with low expression of MTAP/CDKN2A/2B (indicative of chr9 p21.3 loss) had a significantly lower response rate to anti-PD-L1 immunotherapy and worse survival than the patients with high expression of MTAP/CDKN2A/2B. This integrative analysis reveals intrinsic MIBC subtypes and biomarkers with prognostic value for the frontline therapies.

scholarly journals LCK and CD3E Orchestrate the Tumor Microenvironment and Promote Immunotherapy Response and Survival of Muscle-Invasive Bladder Cancer Patients

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaonan Zheng ◽  
Xinyang Liao ◽  
Ling Nie ◽  
Tianhai Lin ◽  
Hang Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Prognostic Value ◽  
The Cancer Genome Atlas ◽  
Invasive Bladder Cancer ◽  
Immune Checkpoints ◽  
Muscle Invasive Bladder Cancer ◽  
Gene Correlation ◽  
Multiple Biomarkers ◽  
Muscle Invasive

Background: Studies have demonstrated the significance of multiple biomarkers for bladder cancer. Here, we attempt to present biomarkers potentially predictive of the prognosis and immunotherapy response of muscle-invasive bladder cancer (MIBC).Method: Immune and stromal scores were calculated for MIBC patients from The Cancer Genome Atlas (TCGA). Core differential expression genes (DEGs) with prognostic value were identified and validated using an independent dataset GSE31684. The clinical implications of prognostic genes and the inter-gene correlation were presented. The distribution of tumor-infiltrating immune cells (TICs), the correlation with tumor mutation burden (TMB), and the expression of eight immune checkpoint–relevant genes and CD39 were accordingly compared. Two bladder cancer cohorts (GSE176307 and IMvigor210) receiving immunotherapy were recruited to validate the prognostic value of LCK and CD3E for immunotherapy.Results: 361 MIBC samples from TCGA revealed a worse overall survival for higher stromal infiltration (p = 0.009) but a better overall survival for higher immune infiltration (p = 0.042). CD3E and LCK were independently validated by TCGA and GSE31684 to be prognostic for MIBC. CD3E was the most correlative gene of LCK, with a coefficient of r = 0.86 (p < 0.001). CD8+ T cells and macrophage M1 are more abundant in favor of a higher expression of CD3E and LCK in MIBC and across pan-cancers. Immune checkpoints like CTLA4, CD274 (PD-1), and PDCD1 (PD-L1) were highly expressed in high-CD3E and high-LCK groups for MIBC and also for pan-cancers, except for thymoma. LCK and CD3E had a moderate positive correlation with CD39 expression. Importantly, high-LCK and high-CD3E groups had a higher percentage of responders than the low-expression groups both in GSE176307 (LCK: 22.73vs. 13.64%, CD3E: 22.00 vs. 13.16%) and IMvigor210 cohorts (LCK: 28.19 vs. 17.45%, CD3E: 25.50 vs. 20.13%).Conclusion: CD3E and LCK were potential biomarkers of MIBC. CD3E and LCK were positively correlated with several regular immunotherapy biomarkers, which is supported by real-world outcomes from two immunotherapy cohorts.

901 Non-muscle invasive bladder cancer and circulating tumor cells: Individuation and prognostic value

2012 ◽  
Vol 11 (1) ◽  
pp. e901-e901a
Author(s):  
G.M. Busetto ◽  
R. Giovannone ◽  
G. Antonini ◽  
M. Di Placido ◽  
A. Petracca ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prognostic Value ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals The Prognostic Value of FGFR3 Expression in Patients with T1 Non-Muscle Invasive Bladder Cancer

2021 ◽  
Vol Volume 13 ◽  
pp. 6567-6578
Author(s):  
Danijel Sikic ◽  
Helge Taubert ◽  
Johannes Breyer ◽  
Markus Eckstein ◽  
Veronika Weyerer ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Value ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Role of partial cystectomy for muscle invasive bladder cancer: Impact on morbidity and overall survival, a population-based study, 2006-2017.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16530-e16530
Author(s):  
Natasza Posielski ◽  
Hannah Koenig ◽  
Nathan Jung ◽  
On Ho ◽  
John Paul Flores ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Population Based ◽  
Pelvic Lymphadenectomy ◽  
Partial Cystectomy ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Full Cohort ◽  
Nccn Guidelines ◽  
Muscle Invasive

e16530 Background: National Comprehensive Cancer Network (NCCN) guidelines state partial cystectomy (PC) may be offered in select patients with clinical T2 (cT2) muscle invasive bladder cancer (MIBC) utilizing neoadjuvant chemotherapy (NAC) and pelvic lymphadenectomy (PLND). Our objective was to investigate utilization and survival outcomes of PC in a large contemporary cohort. Methods: Propensity matching was used to compare pathological and surgical outcomes in non-metastatic MIBC patients in the National Cancer Database undergoing PC or radical cystectomy (RC). Multivariate logistic regression was used to determine predictors of NAC, LND, peri-operative morbidity and mortality outcomes. This analysis was repeated in the subset with cT2 MIBC. Results: Of 31,306 T2-T4N0M0 patients, 1543 (4.9%) underwent PC. PC use was higher in older patients and most often (85%) performed for cT2 disease. The PC group was less likely to receive standard of care including NAC (11.4 vs 27.9%, p<0.001) and PLND (58.7 vs 92.5%, p<0.001) than the RC group. Pathological ≥T3 disease (pT3) was found in 39.4% and pos. nodes in 6.9% of PCs. Positive margins were higher in PC, 15.7 vs 10.6%, p<0.001. PC patients had shorter inpatient stay (4.2 vs 8.7 days, p<0.001), lower 30-day readmission (6.7 vs 9.6%, p<0.001), and decreased 30- and 90-day mortality (1.3 vs 1.8%, p<0.001 & 4.8 vs 4.9%, p=0.04). PC was an independent predictor of lack of NAC (OR 0.49, p<0.001) and PLND (OR 0.11, p<0.001), shorter LOS (b -4.66, <0.001), readmission rate (OR 0.72, p<0.001), and improved 30- and 90- day mortality (OR 0.55 & 0.75, p<0.001). In cT2 patients only: PLND and NAC were less utilized in PC (p<0.001), 32% were ≥pT3 and 6.6% node pos. In both full cohort and cT2 subset, PC was associated with slight improvement in time to mortality (Table) and overall survival (OS) (OR 1.44, p<0.001). Conclusions: PC is rarely used in treatment of MIBC. Despite guidelines, NAC and PLND are underutilized in PC. Care is required in selecting patients for PC as up to one third of cT2 patients have ≥pT3. In these likely highly selected patients, PC had lower peri-operative mortality and comparable OS to RC. Selection bias may play a role in these results and further investigation is needed to determine optimal candidates for PC.[Table: see text]

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