How Gastritis Turns into Cancer and the Biomarkers That Can Save Lives
Gastric cancer remains one of the most lethal malignancies worldwide, but what makes it particularly dangerous is its silent progression from a common stomach inflammation to full-blown cancer.
The journey to gastric cancer doesn't happen overnight. It follows a multi-stage process known as the Correa cascade, named after the scientist who first described this stepwise progression. This pathway begins with chronic non-atrophic gastritis, often triggered by Helicobacter pylori infection, which then advances to chronic atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately carcinoma 1 4 .
Think of this process as a series of warning signs along a dangerous road. Chronic inflammation orchestrates various cellular changes, including loss of epithelial cell polarity, disruption of intercellular junctions, and detachment from the basement membrane. These changes precipitate what scientists call epithelial-mesenchymal transition (EMT) - a process that enables cells to migrate and invade surrounding tissues 1 . Gastric precancerous lesions, particularly intestinal metaplasia and dysplasia, represent pivotal stages in this malignant transformation from chronic gastritis to gastric cancer 1 .
In 2025, a significant research breakthrough identified CHI3L1 as a central driver in the gastritis-to-cancer transformation. Using sophisticated machine learning approaches on gastric cancer datasets, scientists pinpointed this protein as playing a critical role across the entire disease spectrum 1 .
Researchers employed a comprehensive approach to unravel the molecular mechanisms behind gastric cancer development:
The study yielded several critical findings with profound implications:
| Gene | Full Name | Potential Role in Cancer |
|---|---|---|
| CHI3L1 | Chitinase-3-like protein 1 | Central driver activating CD44-β-catenin pathway |
| MMP12 | Matrix metalloproteinase-12 | Tissue remodeling and invasion |
| CXCL6 | C-X-C motif chemokine ligand 6 | Inflammation and cell migration |
| IDO1 | Indoleamine 2,3-dioxygenase 1 | Immune suppression |
| CCL20 | C-C motif chemokine ligand 20 | Inflammation and recruitment of immune cells |
Beyond CHI3L1, researchers have identified several other promising biomarkers that could transform gastric cancer screening.
A 2025 study investigated five protein biomarkers - COL10A1, GKN1, GKN2, LIPF, and REG4 - for their ability to detect gastric cancer early. The researchers found that using these markers in combination (referred to as 5 MP) significantly improved diagnostic accuracy 3 .
| Comparison Groups | Area Under Curve (AUC) | Clinical Significance |
|---|---|---|
| Control vs. Early Gastric Cancer | 0.890 | Excellent discrimination |
| Benign Gastric Disease vs. Early Gastric Cancer | 0.854 | Strong ability to distinguish |
| Precancerous Lesions vs. Gastric Cancer | 0.834 | Good identification |
| Precancerous Lesions vs. Early Gastric Cancer | 0.839 | Effective detection |
Perhaps one of the most patient-friendly advances comes from salivary proteomics research. A 2025 study identified four key proteins - S100A8, S100A9, CST4, and CST5 - that show consistent differential expression in the saliva of gastric cancer patients compared to healthy controls 9 .
In clinical practice, several biomarkers have already established their value in guiding targeted therapies for gastric cancer 7 8 :
| Biomarker | Testing Method | Targeted Therapy | Approval Status |
|---|---|---|---|
| HER2 | IHC and ISH | Trastuzumab, Trastuzumab deruxtecan | Approved since 2010 |
| PD-L1 | IHC | Pembrolizumab, Nivolumab | Approved for advanced disease |
| dMMR/MSI | IHC or PCR | Pembrolizumab | Approved in refractory setting |
| CLDN18.2 | IHC | Zolbetuximab | Approved in 2024 (US and Japan) |
Modern gastric cancer research relies on sophisticated tools and methodologies:
Public repositories of genomic data that allow researchers to analyze gene expression patterns across different disease stages 1 .
Random forest, support vector machine, and other AI tools that can identify complex patterns in large datasets beyond human capability 1 .
Technology that enables researchers to identify which specific cell types are producing key proteins like CHI3L1 1 .
Platforms that allow simultaneous analysis of protein expression across hundreds of tissue samples 1 .
Miniature 3D tissue structures grown from stem cells that mimic organ functionality, enabling better laboratory modeling 1 .
iTRAQ and PRM methods used to identify and validate candidate biomarkers with high sensitivity and specificity 9 .
The identification of specific biomarkers involved in the gastritis-to-cancer transformation represents a paradigm shift in gastric cancer management. Instead of waiting for symptoms to appear, clinicians may soon be able to intercept the disease process early using simple blood or saliva tests.
Diagnosis often occurs at advanced stages when treatment options are limited and prognosis is poor.
Implementation of biomarker panels for high-risk populations, enabling earlier detection and intervention.
Development of targeted therapies based on specific molecular pathways identified through biomarker research.
Widespread screening programs using non-invasive methods like saliva tests, potentially making gastric cancer a preventable disease for many.
These advances, coupled with a deeper understanding of the molecular events driving cancer progression, offer hope for dramatically reducing the global burden of this deadly disease.
The silent transformation from gastritis to cancer may soon lose its stealth, thanks to these remarkable scientific advances that are lighting up the dangerous pathway and providing new tools to stop cancer before it takes hold.