A prognostic signature based on genes associated with m6A/m5C/m1A/m7G modifications and its immunological characteristics in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by a high incidence and mortality rate. Despite advancements in therapeutic interventions, the prognosis for renal cancer patients remains suboptimal. Of late, methylation modifications have emerged as promising molecular targets for tumor assessment and treatment, yet their potential has not been fully investigated in the context of ccRCC. Transcriptomic and clinical data were extracted from The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress databases, leading to the identification of 57 methylation-related genes (MRGs). Utilizing DESeq2 analysis, Cox regression analysis, and the LASSO regression algorithm, a Methylation-Related Risk Score (MARS) was constructed. Cluster analysis, Gene Ontology (GO) analysis, clinical feature analysis, immune infiltration analysis, and mutation analysis were further employed to evaluate the model. Our investigation identified six pivotal prognostic MRGs and established a risk score predicated on m6A/m5C/m1A/m7G regulatory factors. This score was validated across two external cohorts and can be utilized to assess individual immune infiltration statuses and predict responses to immunotherapy. Moreover, cluster analysis delineated two distinct m6A/m5C/m1A/m7G gene clusters. We have developed and validated a robust prognostic signature based on genes associated with m6A, m5C, m1A, and m7G modifications. This gene signature demonstrates significant prognostic value in assessing survival outcomes, clinical characteristics, immune infiltration, and responses to immunotherapy in ccRCC patients. This finding provides valuable insights for refining precision treatment strategies.

Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of kidney cancer, accounts for approximately 70% to 80% of all cases. Histone deacetylase 10 (HDAC10) belongs to the HDAC class IIb subgroup, one of the histone deacetylases (HDAC) family. Previous studies suggest that HDAC10 may regulate the development of multiple tumor types. The specific molecular mechanisms employed by HDAC10 in the etiology of ccRCC still need to be discovered. METHODS: The analysis included examining HDAC10 expression levels and their clinical importance within a cohort of inpatients and ccRCC patients documented in the Tumor Genome Atlas (TCGA). Moreover, the biological functions and underlying molecular mechanisms of HDAC10 were investigated. RESULTS: HDAC10 showed increased expression in ccRCC tumor tissues. Subsequent analysis revealed overexpression of HDAC10 was associated with advanced clinical phenotype and unfavorable prognosis. The absence of HDAC10 significantly decreased ccRCC cell proliferation and migration capabilities. Mechanistic research suggests that HDAC10 may promote RCC development by activating the Notch-1 pathway and downregulating PTEN expression levels. CONCLUSION: In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.