Abstract 168P
Background
Although many treatment options have been adopted in patients with metastatic hormone sensitive prostate cancer (mHSPC), such as early docetaxel and AR-targeting therapy, there are currently no optimal biomarkers to guide treatment in these patients. Here, we sought to define transcriptomic landscape in mHSPC patients treated by either early docetaxel or abiraterone acetate by performing RNA sequencing.
Methods
Transcriptomic profiling of 52 mHSPC was performed by whole transcriptomic sequencing (WTS). For molecular classification, NMF (Non-negative Matrix Factorization) algorithm was used. For perform Gene Set Enrichment Analysis (GSEA), the Hallmark gene sets from the Molecular Signatures Database (MSigDB) were used. Gene sets in this study such as oncogenes, tumor suppressor genes (TSGs), chromosomal instability (CIN25, CIN70), human embryonic stem cell (hES) were used. Single sample Gene Set Enrichment Analysis (ssGSEA) was computed using the “GSVA” package. Gene ontology (GO) analysis was performed David website. Data processing and analysis were performed using R/Bioconductor libraries.
Results
We classified 52 mHSPC patients into two molecular subtypes by using NMF algorithm, particularly subtype1 (S1) and subtype2 (S2), respectively. Of note, S2 had significantly shorter survivals (r-PFS, PSA-PFS, FFS, and Time to CRPC) compared to S1. Additionally, S2 was primarily characterized as highly mitotic cell cycle and cytokinesis. S1 was characterized by metabolic process. Next, ssGSEA and GSEA using Hallmark gene sets showed that G2M checkpoint, E2F targets, and MYC targets were significantly enriched in the S2. Besides, gene sets including oncogenes, TSGs, CIN25/70, hES associated with an aggressive phenotype were activated S2. Up-regulated genes in S2 was associated with poor prognosis using independent two data sets, and was activated primary prostate tissues and metastatic prostate tissues.
Conclusions
In sum, this study demonstrated the utility of molecular subtyping based on transcriptomic analysis to guide prognostication and potential selection of patients in mHSPC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Research Foundation of Korea.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
187P - BUB1 (2530C>T) polymorphism and expression affects chemotherapy response and predicts poor prognosis in advanced epithelial ovarian cancer
Presenter: Sinjini Sarkar
Session: Poster viewing 03
188P - Spatial transcriptomic analysis of tumor tissue in ovarian cancer patients treated with neoadjuvant chemotherapy
Presenter: Irina Larionova
Session: Poster viewing 03
189P - LncRNA NKILA as a negative regulator of NFkB in ascites in ovarian cancer
Presenter: Dinara Dolgova
Session: Poster viewing 03
190P - Real-world applications of poly (ADP-ribose) polymerase inhibitors for ovarian cancer: A single-center study in China
Presenter: dengfeng wang
Session: Poster viewing 03
191P - Phase II study of sodium valproate in combination with oral etoposide in platinum-resistant ovarian cancer
Presenter: N Thejeswar
Session: Poster viewing 03
192P - Human epididymis protein 4 as a predictor of response to neoadjuvant chemotherapy in epithelial ovarian cancer
Presenter: Sarada Planjery
Session: Poster viewing 03
193P - Experience with olaparib in the treatment of BRCA-associated tumors in real clinical practice: Experience of re-challenge mode of olaparib usage
Presenter: Alexander Sultanbaev
Session: Poster viewing 03
194P - A study of the treatment response of concomitant external beam radiotherapy (EBRT) and intracavitary brachytherapy in the management of locally advanced carcinoma of uterine cervix
Presenter: Asish Chowdhury
Session: Poster viewing 03
195P - Awareness of human papillomavirus (HPV) infection, cervical cancer (CC), and vaccine among females in Sultanate of Oman
Presenter: Abdulrahman Al-Mirza
Session: Poster viewing 03
196P - Short course brachytherapy in locally advanced cervical cancer: Safety and response rate
Presenter: Maryam Garousi
Session: Poster viewing 03