Abstract 225P
Background
Common evolution of non-muscle invasive bladder cancer (NMIBC) is local recurrence or progression to muscle invasive bladder cancer (MIBC). Some patients (pts) with NMIBC might develop metastases without progression to MIBC. Clinical evolution of these atypical presentations is unknown. Bladder cancer over the last 5 years has surged by over 13% in India. 50-70% of NMIBC cases recur, and around 10-20% progress to MIBC. Challenge in treatment is identifying the patients with mutations or gene expression patterns for targeted therapy, which is not feasible for all owing to high cost. While omics categorized Western patients, molecular landscape of Indian NMIBC remains incomplete. Herein we report a potential predictive signature, derived by combining transcriptome and whole exome sequencing data of a cohort of NMIBC patients treated in our centre.
Methods
From 2018 to 2021, 25 pts treated at our centre were included for the study, which has been approved by Institutional Ethics committee. Median age at diagnosis was 64Y. 88% received intravesical BCG. 60% were T1 stage and recurrence rate 48%. RNA sequencing and whole exome sequencing were performed on 25 primary NMBIC tumors. Machine learning model was used to predict recurrence status. Mutational status between recurrent and non-recurrent patients was also obtained. The gene expression signature was validated in external datasets including GSE13507 and GSE154261.
Results
435 genes were differentially expressed between recurred and non-recurred patients (p<0.05). Machine learning model predicted recurrence with 90% accuracy. Top pathways upregulated include signalling by nuclear receptors, Shigellosis etc. Downregulated include cell adhesion, PIK-AKT, and ECM reorganization. Validation in external dataset correlated positively with p<0.05. In addition to most previously reported signatures and APOBEC, we also found mutations in FGFR3, ABC transporters, and DAMP, differentially regulated between recurred vs non recurred patients.
Conclusions
We identified novel differentially regulated genes and mutations in genes that predicts recurrence with 90% accuracy. Further analysis in a larger set is underway to complete the validation of the predictive model.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sri Shankara Cancer Hospital and Research Center.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
452P - The relationship between BCG immunotherapy and oxidative stress parameters in patients with non-muscle invasive bladder cancer
Presenter: Mukul Singh
Session: Poster Display
Resources:
Abstract
453P - Palonosetron plus megestrol acetate verses palonosetron plus dexamethasone in preventing moderately emetogenic chemotherapy-induced nausea and vomiting: A randomized, multicenter, crossover, phase II trial
Presenter: Qiaoqi Li
Session: Poster Display
Resources:
Abstract
454P - A multicenter randomized open-label phase II study investigating optimal antiemetic therapy for patients with advanced/recurrent gastric cancer treated with trastuzumab deruxtecan (T-DXd): EN-hance study
Presenter: Akira Ooki
Session: Poster Display
Resources:
Abstract
455P - Assessing model-predicted neurokinin-1 (NK1) receptor occupancy (RO) of netupitant to support efficacy over an extended time period
Presenter: Matti Aapro
Session: Poster Display
Resources:
Abstract
456P - Oxycodone/naloxone in moderate-to-severe cancer pain: A phase III study in China
Presenter: Ping Lu
Session: Poster Display
Resources:
Abstract
457P - Anticoagulation for terminal cancer patients with cancer associated venous thromboembolism
Presenter: Sang Bo Oh
Session: Poster Display
Resources:
Abstract
458P - Association between TSPAN15 and SLC44A2 genetic polymorphisms and venous thromboembolism in cancer patients
Presenter: Alshimaa Al Hanafy
Session: Poster Display
Resources:
Abstract
459P - Association between national health screening program and undertreatment of dyslipidemia in cancer survivors: A cross-sectional study
Presenter: Sujeong Shin
Session: Poster Display
Resources:
Abstract
460P - Group to grow: A systematic review of group-based interventions for post-traumatic growth on cancer patients
Presenter: Dyta William
Session: Poster Display
Resources:
Abstract
461P - A randomized controlled trial of yoga in locally advanced non-small cell lung cancer patients receiving chemoradiotherapy
Presenter: Indranil Khan
Session: Poster Display
Resources:
Abstract