scholarly journals A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiangkun Wu ◽  
Daojun Lv ◽  
Chao Cai ◽  
Zhijian Zhao ◽  
Ming Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Tp53 Mutation ◽  
Low Risk ◽  
Prognostic Signature ◽  
Muscle Invasive Bladder Cancer ◽  
Mutation Status ◽  
Prognostic Group ◽  
Muscle Invasive ◽  
Geo Database

BackgroundTP53 gene mutation is one of the most common mutations in human bladder cancer (BC) and has been implicated in the progression and prognosis of BC.MethodsRNA sequencing data and TP53 mutation data in different populations and platforms were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to determine and validate a TP53-associated immune prognostic signature (TIPS) based on differentially expressed immune-related genes (DEIGs) between muscle-invasive bladder cancer (MIBC) patients with and without TP53 mutations.ResultsA total of 99 DEIGs were identified based on TP53 mutation status. TIPS including ORM1, PTHLH, and CTSE were developed and validated to identify high-risk prognostic group who had a poorer prognosis than low-risk prognostic group in TCGA and GEO database. The high-risk prognostic group were characterized by a higher abundance of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages than the low-risk prognostic group. Moreover, they exhibited a lower abundance of CD56bright NK cells, higher expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2, as well as being more likely to respond to anti–PD-1, and neoadjuvant chemotherapy than the low-risk prognostic group. Based on TIPS and other clinical characteristics, a nomogram was constructed for clinical use.ConclusionTIPS derived from TP53 mutation status is a potential prognostic signature or therapeutic target but additional prospective studies are necessary to confirm this potential.

scholarly journals Recurrence and progression of non-muscle invasive bladder cancer following trans-urethral resection of bladder tumour with adjuvant intravesical chemo-immunotherapy

2020 ◽  
Vol 10 (3) ◽  
pp. 34-38
Author(s):  
Ashok Kumar Kunwar ◽  
Kabir Tiwari ◽  
Sanjesh Bhakta Shrestha ◽  
Srijana Thapa ◽  
Ashish Kumar Panthee ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Effective Treatment ◽  
Risk Group ◽  
Bladder Tumour ◽  
Low Risk ◽  
Invasive Bladder Cancer ◽  
Intermediate Risk ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Background: Trans-urethral resection of bladder tumor is an essential diagnostic tool as well as effective treatment modality for non-muscle invasive bladder cancer. We aimed to evaluate the recurrence and progression of the non-muscle invasive bladder cancer in Nepalese patients. Methods: This was a retrospective study of 43 patients with non-muscle invasive bladder cancer, who underwent trans-urethral resection of bladder tumour followed by adjuvant intravesical instilla­tion of chemo or immunotherapy between January, 2013 to December, 2018. Patients were divided into low, intermediate and high-risk groups according to the clinical and pathological factors used by the European Organization for Research and Treatment of Cancer scoring system. Outcomes were calculated in terms of recurrence and progression in each group. Results: Out of 43 patients, 11 (25.58%) patients had low risk, 18 (41.86%) patients had intermediate risk and 14 (32.56%) patients had high risk of recurrence categories. No recurrence and progression of the disease noted in low risk group. In the intermediate risk group, out of 18 patients, 4 (22.2%) patients developed recurrence and 2 (11.1%) patients had progression of disease. In high risk group, out of 14 patients, 4 (26.8%) patients developed recurrence and 2 (14%) patients developed progres­sion of the disease. Conclusions: Even in a low volume centre of bladder cancer, effective treatment for non-muscle inva­sive bladder cancer with trans-urethral resection of bladder tumour followed by adjuvant intravesical chemo or immunotherapy can be given safely to reduce recurrence and progression of the disease.

scholarly journals Advancements in Intravesical Chemotherapy in Non-Muscle Invasive Bladder cancer

2021 ◽  
Author(s):  
Ankur Mittal ◽  
Vikas Kumar Panwar ◽  
Gurpremjit Singh
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Low Risk ◽  
Intravesical Chemotherapy ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Risk Patients ◽  
Bcg Failure ◽  
Significant Stage ◽  
Muscle Invasive

The treatment for non-muscle-invasive bladder cancer is transurethral resection of bladder cancer followed by intravesical chemotherapy or BCG. There have been various advancements in low risk, intermediate risk, high risk, and BCG failure cases of non-muscle invasive bladder cancer. There has been increased research on hyperthermia and intravesical chemotherapy, new agents like apaziquone, use of gemcitabine in low-risk cases, and combination chemotherapy in cases of BCG failure. Combining docetaxel and gemcitabine has taken a significant stage because of BCG shortage in some parts of the world. This chapter will discuss the latest advancements in intravesical chemotherapy in low, intermediate, and high-risk patients.

scholarly journals A Novel Immune-Gene Pair Signature Revealing the Tumor Microenvironment Features and Immunotherapy Prognosis of Muscle-Invasive Bladder Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaonan Zheng ◽  
Xianghong Zhou ◽  
Hang Xu ◽  
Di Jin ◽  
Lu Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Gene Pair ◽  
Risk Group ◽  
Low Risk ◽  
Survival Outcomes ◽  
Related Gene ◽  
Muscle Invasive Bladder Cancer ◽  
Immune Related Gene ◽  
Muscle Invasive

Immunotherapy has been a milestone for muscle-invasive bladder cancer (MIBC), but only a small portion of patients can benefit from it. Therefore, it is crucial to develop a robust individualized immune-related signature of MIBC to identify patients potentially benefiting from immunotherapy. The current study identified patients from the Cancer Genome Atlas (TCGA) and immune genes from the ImmPort database, and used improved data analytical methods to build up a 45 immune-related gene pair signature, which could classify patients into high-risk and low-risk groups. The signature was then independently validated by a Gene Expression Omnibus (GEO) dataset and IMvigor210 data. The subsequent analysis confirmed the worse survival outcomes of the high-risk group in both training (p < 0.001) and validation cohorts (p = 0.018). A signature-based risk score was proven to be an independent risk factor of overall survival (p < 0.001) and could predict superior clinical net benefit compared to other clinical factors. The CIBERSORT algorithm revealed the low-risk group had increased CD8+ T cells plus memory-activated CD4+ T-cell infiltration. The low-risk group also had higher expression of PDCD1 (PD-1), CD40, and CD27, and lower expression of CD276 (B7-H3) and PDCD1LG2 (PD-L2). Importantly, IMvigor210 data indicated that the low-risk group had higher percentage of “inflamed” phenotype plus less “desert” phenotype, and the survival outcomes were significantly better for low-risk patients after immunotherapy (p = 0.014). In conclusion, we proposed a novel and promising prognostic immune-related gene pair (IRGP) signature of MIBC, which could provide us a panoramic view of the tumor immune microenvironment of MIBC and independently identify MIBC patients who might benefit from immunotherapy.

scholarly journals Intratumoral heterogeneity of surrogate molecular subtypes in urothelial carcinoma in situ of the urinary bladder: implications for prognostic stratification of high-risk non-muscle-invasive bladder cancer

2021 ◽  
Author(s):  
Stefan Garczyk ◽  
Felix Bischoff ◽  
Ursula Schneider ◽  
Reinhard Golz ◽  
Friedrich-Carl von Rundstedt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Carcinoma In Situ ◽  
Molecular Subtypes ◽  
Smoking Status ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Prognostic Stratification ◽  
Muscle Invasive

AbstractReliable factors predicting the disease course of non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) are unavailable. Molecular subtypes have potential for prognostic stratification of muscle-invasive bladder cancer, while their value for CIS patients is unknown. Here, the prognostic impact of both clinico-pathological parameters, including CIS focality, and immunohistochemistry-based surrogate subtypes was analyzed in a cohort of high-risk NMIBC patients with CIS. In 128 high-risk NMIBC patients with CIS, luminal (KRT20, GATA3, ERBB2) and basal (KRT5/6, KRT14) surrogate markers as well as p53 were analyzed in 213–231 biopsies. To study inter-lesional heterogeneity of CIS, marker expression in independent CIS biopsies from different bladder localizations was analyzed. Clinico-pathological parameters and surrogate subtypes were correlated with recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Forty-six and 30% of CIS patients exhibited a luminal-like (KRT20-positive, KRT5/6-negative) and a null phenotype (KRT20-negative, KRT5/6-negative), respectively. A basal-like subtype (KRT20-negative, KRT5/6-positive) was not observed. A significant degree of inter-lesional CIS heterogeneity was noted, reflected by 23% of patients showing a mixed subtype. Neither CIS surrogate subtype nor CIS focality was associated with patient outcome. Patient age and smoking status were the only potentially independent prognostic factors predicting RFS, PFS, OS, and PFS, respectively. In conclusion, further clarification of heterogeneity of surrogate subtypes in HR NMIBC and their prognostic value is of importance with regard to potential implementation of molecular subtyping into clinical routine. The potential prognostic usefulness of patient age and smoking status for high-risk NMIBC patients with CIS needs further validation.

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