Related Experiment Video
Updated: Aug 17, 2025
07:47
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
1.6K
ACTA2 Expression Predicts Survival and Is Associated with Response to Immune Checkpoint Inhibitors in Gastric Cancer
Sunho Park1, John D Karalis2, Changjin Hong1
1Department of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, Florida.
Summary
Alpha-smooth muscle actin (ACTA2) expression predicts survival and response to immune checkpoint inhibitors (ICI) in gastric cancer. Lower ACTA2 in cancer-associated fibroblasts correlates with better ICI response.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Gastric cancer remains a significant health challenge with limited treatment options.
- Immune checkpoint inhibitors (ICIs) have shown promise but predicting response remains difficult.
- Identifying reliable biomarkers for overall survival (OS) and ICI response is crucial for personalized treatment strategies.
Purpose of the Study:
- To identify biomarkers predicting overall survival (OS) and response to immune checkpoint inhibitors (ICIs) in gastric cancer patients.
- To investigate the association between tumor ACTA2 expression and patient outcomes.
- To explore the role of ACTA2 in different cellular compartments concerning ICI response.
Main Methods:
- Retrospective analysis of multiple independent gastric cancer cohorts.
- Bulk mRNA sequencing to assess tumor ACTA2 expression and its correlation with OS.
- Single-cell RNA sequencing (scRNA-seq) and digital spatial profiling to compare ICI responders and non-responders.
Main Results:
- Elevated tumor ACTA2 expression was independently associated with worse OS in discovery (HR 1.28) and validation cohorts (HR 1.52).
- Patients with low ACTA2 expression showed higher response rates to ICIs (56%) compared to those with high ACTA2 expression (25%).
- Lower ACTA2 expression in cancer-associated fibroblasts (CAFs) was observed in ICI responders compared to non-responders.
Conclusions:
- Tumor ACTA2 expression serves as a prognostic biomarker for survival in gastric cancer.
- ACTA2 expression within CAFs, not other cellular compartments, is linked to ICI response.
- Targeting ACTA2 in CAFs may represent a future therapeutic strategy for improving ICI efficacy in gastric cancer.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
02:07Tumor Progression
6.4K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.4K
01:21Cancer Survival Analysis
413
Cancer survival analysis focuses on quantifying and interpreting the time from a key starting point, such as diagnosis or the initiation of treatment, to a specific endpoint, such as remission or death. This analysis provides critical insights into treatment effectiveness and factors that influence patient outcomes, helping to shape clinical decisions and guide prognostic evaluations. A cornerstone of oncology research, survival analysis tackles the challenges of skewed, non-normally...
413