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

Sep 22, 2026

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Advanced gastric and gastroesophageal junction cancers (GC/GEJCs) show diverse molecular signatures, creating a need for precise evaluations to find actionable therapeutic targets. Although whole-transcriptome sequencing (WTS) can clarify molecular complexity, its clinical relevance remains insufficiently defined. This study assessed the relationship between immunohistochemistry (IHC) and WTS, compared their clinical significance, and identified targets not detectable by IHC alone. In 140 patients, six key biomarkers were evaluated using IHC and WTS within MONSTARSCREEN-2.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Study rationale and background

Clinical need for molecular targets

Role of IHC and multiomics (WES/WTS)

DOI: 10. 1111/cas.16109 OR I G I NAL ART I C L E Whole-transcriptome sequencing in advanced gastric or gastroesophageal cancer: A deep dive into its clinical potential Tadayoshi Hashimoto1,2 | Yoshiaki Nakamura1,2 | Saori Mishima1 | Izuma Nakayama1 | Daisuke Kotani1 | Akihito Kawazoe1 | Yasutoshi Kuboki1 | Hideaki Bando1,2 | Takashi Kojima1 | Naoko Iida2 | Taro Shibuki2,3 | Mitsuho Imai2 | Takao Fujisawa2,4 | Michiko Nagamine5 | Naoya Sakamoto5,6 | Takeshi Kuwata5,7 | Takayuki Yoshino1 | Kohei Shitara1 1Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan 2Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan 3 Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan 4Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan 5Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan 6Division of Pathology, Exploratory Oncology Research and Clinical Research Center, Kashiwa, Japan 7Department of Genetic Medicine and Services, National Cancer Center Hospital East, Kashiwa, Japan Correspondence Yoshiaki Nakamura, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan. [Email:](Email: yoshinak@east. ncc.go.jp)[ yoshinak@east. ncc.go.jp](Email: yoshinak@east. ncc.go.jp) Funding information SCRUM-Japan Funds; Japan Agency for Medical Research and Abstract 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 MONSTARSCREEN-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 IHCand 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 inpatients displaying negative targetable biomarkers via IHC. Our findings highlighted the significant correlation between IHC and WTS, reinforcing the clinical utility of Abbreviations: CIN, chromosomal instability; CLDN18, Claudin 18; CPS, combined positive score; EBV, Epstein–Barr virus; EGFR, epidermal growth factor receptor; GC, gastric cancer; GEJC, gastroesophageal junction cancer; GS, genome stable; HER2, human epidermal growth factor receptor 2; ICI, immune checkpoint inhibitors; IHC, immunohistochemistry; MET, mesenchymal–epithelial transition; MMR, mismatch repair; PD-L1, programmed death-ligand 1; PFS, progression-free survival; RTK, receptor tyrosine kinase; TCGA, The Cancer Genome Atlas; TPM, transcript per million; W

FAQs

What is the main objective of the study?

To evaluate how immunohistochemistry (IHC) correlates with whole-transcriptome sequencing (WTS), compare their clinical significance, and identify therapeutic targets that IHC alone may miss.

Which biomarkers were assessed in the patient cohort?

Six pivotal biomarkers were evaluated by IHC, including CLDN18, HER2 (ERBB2), multiple receptor tyrosine kinases (RTKs), and PD-L1.

What did the study find regarding the link between IHC and WTS?

Significant correlations were observed between IHC and WTS across all six pivotal biomarkers, and WTS revealed elevated expression of key biomarkers in patients whose targetable biomarkers were negative by IHC.

Sep 22, 2026

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