مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
Identifying RARRES1 as a Key Biomarker in Cutaneous Melanoma: A Bioinformatic and Experimental Approach
Identifying RARRES1 as a Key Biomarker in Cutaneous Melanoma: A Bioinformatic and Experimental Approach
Fereshteh Arefi,1,*
1. Biology Department, Faculty of Biosciences, Tehran North Branch, Islamic Azad University, Tehran, Iran
Introduction: Cutaneous melanoma of the skin (SKCM) is a very aggressive type of skin cancer that has a negative outlook. It remains a major health concern with rising global incidence rates. Efforts to reduce it have been ineffective. The highest rates are in Australia, while the lowest are in Asia. Melanoma is the twelfth most common cancer worldwide, with higher rankings in Europe and the USA. Incidence rates are roughly similar for men and women. While RARRES1 has been studied in other cancers, its role in SKCM remains unclear. This study aims to investigate the expression, function, and clinical significance of RARRES1 in SKCM. By analyzing gene expression data, genomic alterations, and promoter methylation, the study explored the potential association between RARRES1 and SKCM progression. Additionally, functional experiments were conducted to evaluate the impact of RARRES1 on SKCM cell behavior and tumor growth.
Methods: This study employed a comprehensive approach to investigate the role of RARRES1 in SKCM. The methods included:
Data analysis: Utilizing the GSE15605 dataset from GEO and RNAseq data from TCGA, this study evaluated RARRES1 expression, associated clinical features, prognostic implications, and diagnostic efficacy.
Functional enrichment analysis: Co-expression heatmaps and pathway enrichment analyses (GO, KEGG, GSEA) were performed to identify genes and pathways regulated by RARRES1.
Immune infiltration analysis: Immune cell infiltration levels were analyzed using ssGSEA algorithm and correlated with RARRES1 expression.
Genomic alterations and promoter methylation analysis: cBioPortal, UALCAN, GEO, and EWAS databases were used to assess gene mutations and promoter methylation.
Clinical sample analysis: Skin tissue samples were collected for IHC analysis to assess RARRES1 protein expression.
In vitro experiments: A375 melanoma cells were used to study cell proliferation, migration, apoptosis, cell cycle, ROS production, and autophagic flux.
In vivo experiments: RARRES1-overexpressing A375 cells were injected into nude mice to evaluate tumor growth.
Statistical analysis: Appropriate statistical tests were used to analyze the data, and results were visualized using GraphPad Prism.
Ethical considerations, including informed consent and animal welfare, were strictly adhered to throughout the study.
Results: This study investigated the role of RARRES1 in skin cutaneous melanoma (SKCM). Key findings include:
Downregulated in SKCM: RARRES1 expression is significantly lower in SKCM compared to normal tissues.
Poor prognosis: Low RARRES1 expression is associated with worse clinical features and unfavorable prognosis.
Diagnostic potential: RARRES1 has potential as a diagnostic biomarker.
Functional effects: RARRES1 inhibits cell proliferation, migration, and promotes apoptosis.
Immune modulation: RARRES1 is positively correlated with immune cell infiltration.
Genomic alterations: Genetic changes and modifications to the RARRES1 promoter were found to reduce its expression. While mutations were rare, some were identified. Additionally, the DNA region that controls RARRES1 expression was more heavily modified in metastatic melanoma compared to normal tissues.
Regulation of Autophagy and ROS: RARRES1 overexpression induced autophagy but also inhibited autophagosome degradation. This was associated with increased ROS levels and lysosomal dysfunction.
Suppresses tumor growth: RARRES1 overexpression suppresses tumor growth in vivo.
Collectively, these findings suggest that RARRES1 may function as a tumor suppressor and has potential as a prognostic biomarker and therapeutic target for SKCM.
Conclusion: The current research shows that RARRES1 expression is decreased in skin cutaneous melanoma (SKCM) as a result of changes in the genome and methylation of the promoter. Moreover, there is a correlation between decreased RARRES1 expression and worse overall survival. Functional enrichment analysis and laboratory tests indicate that RARRES1 acts as a tumor suppressor by controlling immune cell infiltration, proliferation, migration, apoptosis, and autophagy. These results emphasize the importance of RARRES1 as a useful prognostic biomarker and a hopeful treatment target for SKCM.