Metastatic Pathways in Gastric Cancer

Metastasis in gastric cancer is a multistep process involving local invasion, intravasation, survival in circulation, extravasation and colonisation of distant sites. Tumour cells acquire motile and invasive phenotypes through epithelial–mesenchymal transition, detach from the primary lesion and exploit lymphatic channels, blood vessels and peritoneal cavities to disseminate. Haematogenous spread most commonly targets the liver via the portal circulation, while lymphatic dissemination follows gastric and retroperitoneal nodal chains. Transcoelomic metastasis through exfoliation into the peritoneal cavity underlies widespread peritoneal seeding and ascites formation. Molecular drivers include aberrant adhesion molecules, matrix metalloproteinases and chemokine receptor signalling, while tumour-derived exosomes prepare premetastatic niches. The interplay between cancer cells and stromal elements, notably cancer-associated fibroblasts and immune cells, shapes the microenvironment to support colonisation. Patterns of spread differ by tumour location and histological subtype: cardia cancers favour extraperitoneal sites, whereas diffuse and signet-ring types show peritoneal tropism. Understanding these pathways informs surveillance strategies, prognostic assessment and the development of targeted therapeutic interventions.

Research from Nature Portfolio

Recent studies have demonstrated the power of machine-learning algorithms to predict the risk of distant metastasis in early-stage gastric cancer. A random forest model trained on large registry data accurately stratified patients with T1 gastric adenocarcinoma according to their probability of developing metastases, achieving an area under the receiver-operating characteristic curve above 0.90 in internal validation. Key clinicopathological variables—tumour size, T stage, N stage, grade and anatomical site—emerged as independent predictors. External validation in a separate hospital cohort confirmed the model’s utility, albeit with modestly reduced performance. Concurrent prognostic analyses revealed that surgical resection and adjuvant chemotherapy significantly improved survival among those who developed metastases, highlighting the importance of aggressive multimodal management in high-risk individuals.

Metastatic Pathways in Gastric Cancer publication trend

The graph below shows the total number of articles in metastatic pathways in gastric cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Epithelial–mesenchymal transition (EMT): A cellular programme through which epithelial tumour cells acquire motility and invasiveness by losing polarity and adhesion properties.

Transcoelomic spread: Dissemination of cancer cells across body cavities, especially into the peritoneal space, via direct exfoliation from the primary site.

Pre-metastatic niche: A supportive microenvironment established at distant organs by tumour-derived factors and exosomes prior to arrival of disseminated tumour cells.

Haematogenous dissemination: The process by which tumour cells enter the bloodstream and travel to distant organs, commonly the liver in gastric cancer.

Cancer-associated fibroblast (CAF): A stromal cell type within the tumour microenvironment that secretes growth factors and matrix remodelling enzymes to facilitate invasion and metastasis.

References

1. Application of machine learning algorithm in predicting distant metastasis of T1 gastric cancer. Scientific Reports (2023).
2. Metastatic spread in patients with gastric cancer. Oncotarget (2016).
3. Frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from gastric cancer: A SEER‐based study. Cancer Medicine (2018).
4. Bone Metastases from Gastric Cancer: What We Know and How to Deal with Them. Journal of Clinical Medicine (2021).