Whole-transcriptome sequencing in advanced gastric or gastroesophageal cancer: A deep dive into its clinical potential.

Autor: Hashimoto T; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan., Nakamura Y; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan., Mishima S; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Nakayama I; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Kotani D; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Kawazoe A; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Kuboki Y; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Bando H; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan., Kojima T; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Iida N; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan., Shibuki T; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Imai M; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan., Fujisawa T; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.; Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Nagamine M; Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan., Sakamoto N; Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan.; Division of Pathology, Exploratory Oncology Research and Clinical Research Center, Kashiwa, Japan., Kuwata T; Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan.; Department of Genetic Medicine and Services, National Cancer Center Hospital East, Kashiwa, Japan., Yoshino T; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Shitara K; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2024 May; Vol. 115 (5), pp. 1622-1633. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1111/cas.16109
Abstrakt: Advanced gastric and gastroesophageal junction cancers (GC/GEJCs) harbor diverse molecular signatures, highlighting the need for intricate evaluations to identify potential therapeutic targets. Although whole-transcriptome sequencing (WTS) has emerged as a useful tool for understanding these molecular intricacies, its clinical implications have yet to be fully elucidated. This study evaluated the correlation between immunohistochemistry (IHC) and WTS, compared their clinical significance, and identified potential therapeutic targets undetectable through IHC alone. We enrolled 140 patients with advanced GC/GEJC and assessed them using IHC for six pivotal biomarkers: claudin-18 (CLDN18), human epidermal growth factor receptor 2 (HER2), multiple receptor tyrosine kinases (RTKs), and programmed death ligand 1 (PD-L1). Concurrently, WTS was employed as part of the analyses in MONSTAR-SCREEN-2, a multicenter multiomics study. IHC analysis revealed 16.4% HER2, 39.3% CLDN18 (2+/3 + ≥75%), and 15.8% PD-L1 (combined positive score ≥ 10) positivity, among other molecular markers. Significant correlations were observed between IHC and WTS for all six pivotal biomarkers. Among nineteen HER2 IHC-positive patients treated with anti-HER2 therapeutics, ERBB2 status in WTS was significantly associated with progression-free survival (ERBB2-high vs. -low: median 9.0 vs. 5.6 months, log-rank p = 0.046). IHC-based molecular profiling revealed significantly high expression of CLDN18 in RTK-negative patients, with 78.4% positive for either CLDN18 or PD-L1. Additionally, WTS revealed elevated expression of pivotal biomarkers in patients displaying negative targetable biomarkers via IHC. Our findings highlighted the significant correlation between IHC and WTS, reinforcing the clinical utility of WTS. A subset with IHC-negative but WTS-positive status may benefit from specific biomarker-targeted therapies.
(© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE