Abstract 341P
Background
Ductal adenocarcinoma (DA) is relatively rare and highly co-existed with prostate adenocarcinoma (AC). The aim of this study is to investigate the distinctive genomic profiles of the patients with DA in contrast to those without it.
Methods
Blood samples were collected from 144 patients (36 harbored DA and 108 without DA) diagnosed between 2017 to 2023 in West China Hospital. We performed cell-free DNA sequencing investigating the genomic differences between patients with (DA (+)) and without DA (DA (-)), and explored the potential associations between mutational status and patients’ prognoses. Pathogenic/likely pathogenic alternations were included for analysis. Homologous recombination deficiency (HRD) scores and tumor mutation burden (TMB) values were also compared between DA (+) and DA (-).
Results
We identified that AR pathway (16/36 [44.4%] vs 24/108 [22.2%], p=0.017) and WNT pathway (6/36 [16.7%] vs 5/108 [4.6%], p=0.029) mutations were significantly enriched in DA (+) compared to DA (-), with the former one featured by FOXA1 (9/36 [25%] vs 5/108 [4.6%], p=0.0012). DDR mutation rate and the HRD scores appeared to be comparable between DA (+) and DA (-). In M1 cohort, SPOP alterations (4/17 [23.5%] vs 3/56 [5.4%], p=0.047) appeared to be statistically more frequent in patients harboring DA. TP53 was associated with deteriorating prognosis for both DA (+) and DA (-) in terms of castration-free survival (CFS).
Conclusions
Our findings provide further genomic insights in prostate cancer with ductal morphology and are instructive for the diagnosis and treatment of DA.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
H. Zeng.
Funding
This work was supported by the National Natural Science Foundation of China (NSFC 82203110, 82172785, and 81974398), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC21020, ZYGD22004), Science and Technology Support Program of Sichuan Province (2021YFS0119), Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences (2022-I2M-C&T-B-098), Bethune Foundation, Oncology Basic Research Program (X-J-2020-016), Bethune Foundation, Urological Oncology Special Research Fund (mnzl202002, mnzl202007) and Postdoctor Research Fund of West China Hospital, Sichuan University (2024HXBH001).
Disclosure
All authors have declared no conflicts of interest.