Immunotherapy is a revolutionary cancer treatment strategy that leverages the body’s immune system to fight cancer. While immune checkpoint inhibitors significantly improve the therapeutic outcomes in many tumors, most cancer patients cannot benefit from these.
The mesenchymal-epithelial transition factor (MET), a proto-oncogene that encodes the tyrosine kinase receptor of the hepatocyte growth factor (HGF), elicits various intracellular signaling cascades, including cell motility, growth & survival, and inflammatory pathways. Aberrant or deregulated MET signaling promotes cancer cell proliferation, survival, and immunosuppression, leading to speculation that MET mutation may impact immunotherapy outcomes and serve as a potential predictive biomarker.
In a recent study published in the Genes & Diseases journal, researchers from Fujian Medical University and the Cancer Center of The Fifth Affiliated Hospital of Sun Yat-Sen University “conducted a comprehensive bioinformatics and clinical analysis to explore the characteristics of MET mutation and its association with the outcomes in pan-cancer immunotherapy.”
To investigate the impact of MET mutation on immunotherapy outcomes, the authors employed a discovery cohort comprising 2539 patients with seven tumor types from 14 datasets and a validation cohort comprising 1610 patients with 10 tumor types. MET mutation was associated with a decreased mortality risk, better progression-free survival, and a higher overall response rate. Furthermore, certain single base substitutions (SBS) such as SBS7a, SBS10b, SBS30, SBS42, and SBS86 were identified “as robust predictive biomarkers for survival in pan-cancer immunotherapy.”
The expression of three key immune checkpoints (CTLA-4, PD-1, and PD-L1) was significantly increased in MET-mutant tumors, with a concomitant increase in the expression of many MHC-related antigen-presenting molecules and co-stimulators. MET mutations were also associated with enhanced immune cell infiltration, especially CD8+ T cells, along with increased levels of most chemokines & their receptors and immune stimulators, suggesting that MET-mutant tumors are immunologically “hot” tumors.
The authors acknowledged several limitations of the study, including i) potential biases or errors in data collected from different centers due to variability among original investigators, ii) a limited sample size of only 12 tumor types, and iii) the absence of molecular experiments to validate the bioinformatics findings.
In conclusion, using multiple bioinformatics and clinical analyses, the authors of this study showed that MET mutation is associated with enhanced tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses, marking it as a versatile positive predictive biomarker in pan-cancer immunotherapy.
Reference
Title of the original paper: Pan-cancer analysis of MET mutation and its association with the efficacy of immune checkpoint blockade
Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.
DOI: https://doi.org/10.1016/j.gendis.2024.101450
# # # # # #
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
Scopus CiteScore: 7.3 | Impact Factor: 6.9
More information: https://www.keaipublishing.com/en/journals/genes-and-diseases/
Editorial Board: https://www.keaipublishing.com/en/journals/genes-and-diseases/editorial-board/
All issues and articles in press are available online in ScienceDirect ( https://www.sciencedirect.com/journal/genes-and-diseases ).
Submissions to Genes & Disease may be made using Editorial Manager ( https://www.editorialmanager.com/gendis/default.aspx ).
Print ISSN: 2352-4820
eISSN: 2352-3042
CN: 50-1221/R
Contact Us: editor@genesndiseases.com
X (formerly Twitter): @GenesNDiseases ( https://x.com/GenesNDiseases )
Genes & Diseases