Signet Ring Cell Carcinoma in Gastric Oncology
Summary
Signet ring cell carcinoma (SRCC) is a distinct histological subtype of gastric cancer characterised by cells containing abundant intracytoplasmic mucin that displaces the nucleus to the periphery, giving a “signet ring” appearance. Although accounting for 10–28% of gastric malignancies, SRCC exhibits unique epidemiological and molecular traits, with rising incidence in both Eastern and Western populations. Clinically, patients often present at younger ages and with advanced disease, reflecting early submucosal spread, diffuse infiltration and a tendency towards linitis plastica. The biological behaviour of SRCC is governed by altered cell adhesion, heightened invasive potential and a profoundly immunosuppressive tumour microenvironment. Genomic investigations have revealed characteristic fusions and mutations, while proteomic and transcriptomic studies highlight activation of pathways such as MAPK and oestrogen signalling. Therapeutic management remains challenging owing to intrinsic chemoresistance and limited biomarker-guided options. Surgical resection remains the cornerstone of curative treatment for localised disease, whereas systemic therapies, including triplet chemotherapy regimens and emerging immunomodulatory approaches, are under active evaluation. Improved understanding of SRCC biology is essential to guide early detection, refine prognostic stratification and develop targeted interventions that may alter the historically poor outcomes associated with this aggressive gastric cancer subtype.
Research from Nature Portfolio
Recent studies have employed single-cell RNA sequencing to delineate the cytological and immune microenvironment features of SRCC. These analyses identify marker genes such as MSMB to distinguish poorly differentiated adenocarcinoma from SRCC and show that SRCC cells display reduced adhesion, elevated immune-evasion capabilities and an immunosuppressive milieu driven by activated MAPK and oestrogen signalling in reciprocal feedback loops. Parallel genomic work has uncovered the CLDN18-ARHGAP26/6 fusion as a recurrent alteration in SRCC, correlating with higher tumour content, female predominance, advanced stage and notably poorer survival. Functional assays demonstrate that this fusion confers resistance to oxaliplatin/fluoropyrimidine regimens, highlighting its role in chemotherapy refractoriness and underscoring the need for alternative therapeutic strategies in fusion-positive tumours.
Signet Ring Cell Carcinoma in Gastric Oncology publication trend
The graph below shows the total number of articles in signet ring cell carcinoma in gastric oncology across all publications each year (not limited to Nature Index journals).
Technical terms
Signet ring cell carcinoma: A gastric cancer subtype with mucin-filled cells displacing the nucleus.
Tumour microenvironment: The complex milieu of immune cells, stroma and signalling factors surrounding a tumour.
Single-cell RNA sequencing: A high-resolution method to profile gene expression in individual cells.
CLDN18-ARHGAP26/6 fusion: A recurrent genomic rearrangement linking CLDN18 to ARHGAP genes in SRCC.
Tumour-associated neutrophils (TANs): Neutrophils recruited to tumours that can promote progression and immunosuppression.
Nomogram: A statistical tool that provides personalised risk predictions based on multiple variables.
References
- Single-cell analysis of gastric signet ring cell carcinoma reveals cytological and immune microenvironment features. Nature Communications (2023).
- IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC). Journal of Translational Medicine (2024).
- A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study. Frontiers in Immunology (2024).
- Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer. Nature Communications (2018).
- Difference Between Signet Ring Cell Gastric Cancers and Non-Signet Ring Cell Gastric Cancers: A Systematic Review and Meta-Analysis. Frontiers in Oncology (2021).
- Epidemiology of Signet Ring Cell Adenocarcinomas. Cancers (2020).
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.