Abstract 175P
Background
Advanced gastric adenocarcinoma with both lymph node and peritoneal metastasis has notoriously poor prognosis. However, molecular mechanism of the metastatic process and potential therapeutic targets remain unknown, hence limiting the development of new therapies.
Methods
We recruited 13 treatment-naïve patients who had gastric adenocarcinoma with concurrent lymph node and peritoneal metastasis. DNA and RNA were extracted from tumor biopsy samples collected from the stomach, lymph node and peritoneum, together with 2 mL of peripheral blood for each patient. Whole exome sequencing (WES) and transcriptome sequencing were performed to generate a comprehensive genomic dataset of our cohort.
Results
Analysis of WES data showed that TP53 and CDH1 were the most frequently mutated genes in both the primary and metastatic tumors. All patients had low tumor mutational burden, but 31% (n=4) showed high level of chromosomal instability (CIN). By constructing tumor phylogenetic trees for each patient, we found evidence supporting two distinct processes of peritoneal dissemination that involved either lymphatic system (n=5) or direct seeding into the peritoneal cavity (n=4). In the RNA sequencing analysis, epithelial-mesenchymal transition (EMT) pathway was found the most significantly altered and segregated the patients into the EMT-high group (n=10) that upregated genes in the EMT pathway, and the non-EMT-high group (n=3).
Conclusions
Multi-omics profiling in this study revealed mutational signature and altered signaling pathways in lymph node and peritoneal metastasis. The results could help identify distinct molecular subtypes among patients, laying foundation for the development of molecular-guided therapeutic strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Medical Genetics Institute, Ho Chi Minh city, Vietna.
Funding
Gene Solutions JSC, Ho Chi Minh city, Vietnam.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
73TiP - Global phase III studies evaluating vepdegestrant in estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer: VERITAC-2 and VERITAC-3
Presenter: Hiroji Iwata
Session: Poster Display
Resources:
Abstract
78P - First-in-human phase I study of TT-00434, an orally available FGFR (1-3) inhibitor in patients with advanced solid tumors
Presenter: Chia Jui Yen
Session: Poster Display
Resources:
Abstract
79P - Accelerated identification of recurrent neoantigens for the development of off-the-shelf cancer vaccines
Presenter: Le Son Tran
Session: Poster Display
Resources:
Abstract
80P - Safety, preliminary efficacy, and pharmacokinetics of HLX26 plus serplulimab in advanced solid tumours: An open-label, dose-escalation phase I study
Presenter: Yanmin Wu
Session: Poster Display
Resources:
Abstract
81P - A first-in-human, multiple dose and dose escalation phase I study to investigate the safety, tolerability and antitumor activity of SmarT cells plus PD-1 blocking antibodies in patients with far advanced/metastatic solid tumors
Presenter: Qin Liu
Session: Poster Display
Resources:
Abstract
82P - NEXUS: A phase I dose escalation study of selinexor plus nivolumab and ipilimumab in Asian patients with advanced/metastatic solid malignancies
Presenter: Gloria Chan
Session: Poster Display
Resources:
Abstract
83P - The updated report of phase I trial of VG2025, a non-attenuated HSV-1 oncolytic virus expressing IL-12 and IL-15/RA payloads, in patients with advanced solid tumors
Presenter: Yinan Shen
Session: Poster Display
Resources:
Abstract
84P - T cell receptor repertoire profiles of tumor -infiltrating lymphocytes improves neoantigen prioritization for personalized cancer immunotherapy
Presenter: Tran Nguyen
Session: Poster Display
Resources:
Abstract
85P - Oligometastatic solid tumors: Disease characteristics and role of local therapies
Presenter: Alshimaa Al Hanafy
Session: Poster Display
Resources:
Abstract
86P - Efficacy and safety of HLX07 monotherapy in advanced cutaneous squamous cell carcinoma: An open-label, multicentre phase II study
Presenter: Changxing Li
Session: Poster Display
Resources:
Abstract