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
383P - Pre-treatment body mass index and neutrophil lymphocyte ratio predict 3-years progression free survival in locally advanced stage nasopharyngeal carcinoma
Presenter: Ni Putu Pusvita Dewi
Session: Poster Display
Resources:
Abstract
384P - Sequential multi-modality strategies for locally advanced betel-nuts related hypopharyngeal cancer in Taiwan
Presenter: Wei-Chen Lu
Session: Poster Display
Resources:
Abstract
385P - The prognostic factors of induction chemotherapy followed by concurrent chemoradiotherapy in patients with HPV associated with oropharyngeal cancer
Presenter: Hyun Jin Bang
Session: Poster Display
Resources:
Abstract
386P - FOLR1 stabilized beta-catenin promotes laryngeal carcinoma progression through EGFR signal
Presenter: Huawei Tuo
Session: Poster Display
Resources:
Abstract
387P - A comprehensive analysis of the oral health status, tobacco use, and cancer prevalence among the tribal communities in India
Presenter: Delfin Lovelina Francis
Session: Poster Display
Resources:
Abstract
388P - Clinicopathological correlation of P53 expression in oral cancers
Presenter: Venkata Madhavi Bellala
Session: Poster Display
Resources:
Abstract
389P - Lack of cross-resistance to erlotinib in human head and neck cancer cells with acquired resistance to cetuximab
Presenter: James A. Bonner
Session: Poster Display
Resources:
Abstract
390P - Epidemiological aspects of the development of oral cancer in the Republic of Uzbekistan
Presenter: Akhrorbek Yusupbekov
Session: Poster Display
Resources:
Abstract
391P - Lip cancer: Racial disparities, treatment modalities and long-term survival outcome in young and adults versus older age patients
Presenter: FathAlrahman Ibrahim
Session: Poster Display
Resources:
Abstract
392TiP - A prospective phase II study of individualized adjuvant therapy in patients with locally advanced hypopharyngeal cancer after neoadjuvant therapy
Presenter: Juyi Wen
Session: Poster Display
Resources:
Abstract