INTERNATIONAL CONGRESS OF
PharmacoGenetics
The Role of RASSF1A Gene Methylation in Lung Cancer and Prediction of Response to Targeted Therapies: A Systematic Review
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AmirMohammad Ganjali,1 Yekta Rezapour,2 Hossein Javid,3,*
1. Student Research Committee, Varastegan Institute for Medical Sciences, Mashhad, Iran
2. Student Research Committee, Varastegan Institute for Medical Sciences, Mashhad, Iran
3. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
- Introduction: Lung cancer, especially non-small cell lung cancer (NSCLC), is the deadliest cancer among people, and the latest statistics show that its mortality is twice as high as that of colorectal cancer. Epigenetics, particularly DNA methylation, plays a crucial role in the advancement of personalized therapies due to its reversible nature. The hypermethylation of the RASSF1A gene can result in the inactivation of this tumor suppressor gene, consequently disrupting cell growth control and promoting the carcinogenic process. Our research aims to investigate the significance of RASSF1A gene methylation in lung cancer and its ability to forecast responses to targeted treatments.
- Methods: This systematic review was performed by searching the PubMed, ScienceDirect, and Scopus databases. The search criteria included studies published between the years 2000 and 2024, those involving human subjects, and articles published in English. In the majority of the studies examined, the methylation status of the RASSF1A gene was evaluated utilizing MSP-PCR or Nested MSP-PCR methodologies. Prior to this analysis, the DNA samples were treated with sodium bisulfite to effectively distinguish between methylated and unmethylated regions. A total of 30 articles were initially identified; however, after a review of the titles and abstracts, 23 articles were excluded due to their lack of relevance to the specific type of cancer being investigated. Ultimately, seven eligible articles were included in the final analysis.
- Results: A thorough review of relevant studies reveals that methylation of the RASSF1A gene is commonly found in individuals diagnosed with lung cancer, especially within the non-small cell lung cancer (NSCLC) subgroup. However, the information available regarding the small cell lung cancer (SCLC) subgroup is either limited or not adequately addressed. While a definitive link between RASSF1A methylation and the success of targeted therapies has not been conclusively proven, there are indications that patients who have a positive response to the therapy show a reduction in methylation levels after chemotherapy. This observation indicates that methylation could affect how individuals respond to drug treatments. Moreover, RASSF1A methylation is linked to a notable reduction in overall survival rates and has been suggested as a potential predictive biomarker in several studies. However, there is scant evidence to support the idea that this methylation can be used as a predictive tool for selecting and personalizing targeted therapies.
- Conclusion: The methylation of the RASSF1A gene in lung cancer, particularly in non-small cell lung cancer (NSCLC), serves as a significant marker for predicting patient outcomes. Its presence is linked to shorter survival times. Research shows that changes in methylation levels during treatment may indicate how well tumors respond to chemotherapy. However, it is still unclear how this relates to targeted therapies. These characteristics highlight the potential of RASSF1A to enhance personalized medicine; monitoring this biomarker before and during treatment could facilitate the selection and adjustment of treatment strategies. However, for the standardization and clinical application of this marker, larger and more carefully designed studies are necessary.
- Keywords: RASSF1A / DNA Methylation / Lung Neoplasms / Carcinoma, Non-Small-Cell Lung / Epigenesis, Genetic
