Integrated analysis of histone modification features in clear cell renal cancer for risk stratification and therapeutic prediction.

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However, few studies have focused on the predictive role of the global histone modification status in ccRCC. A total of 621 patients with complete transcript information and corresponding clinical profiles were obtained from TCGA-KIRC, GSE22541, and EMTAB3267 cohorts. A total of 122 histone modification relevant pathways were derived from MSigDB, and their activation status was quantified using GSVA. Differentially expressed genes (DEGs) were identified and filtrated using univariate Cox regression analysis. The signature was built relied on the least absolute shrinkage and selection operator (LASSO) regression analysis, and evaluated from survival difference, chemotherapy response, and activated pathways. A novel nomogram was established to quantify the probability of death in different patients. Seven risky and fifty-eight protective genes were used in LASSO analysis, and six genes were used to build the histone modification gene (HiMG) signature, which showed significant independent prognostic potential in all three cohorts. The nomogram showed acceptable incremental predictions. CKS2 (p = 0.004) and PD1 (p = 0.002) expression were significantly higher in grade 3 ccRCC than in grades 1-2. CKS2 siRNA in renal cancer cells caused reductions in cellular proliferation, migration, and invasion. Patients with low HiMG may be potential responders to rapamycin, erlotinib and FH535, while AZD6482 and CHIR-99,021 may be more suitable for patients with high HiMG levels. ccRCC histone modification distribution and a clinical signature for prognosis prediction, clinical decision making, and molecular mechanism exploration, were established for risk stratification and personalized treatments.", "claims": [{"id": "claim-method", "statement": "“GSVA, v.3.5” was used to evaluate the activation status of 122 pathways, and for each sample in the TCGA-KIRC cohort, the enrichment score for a specific gene set was calculated to quantify the condition of total gene set activation [25]. Consequently, the transcript profiles in the TCGA-KIRC cohort were deciphered as gene set activation profiles.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38924847", "locator": "sections[5] \"Histone modification pathways collection and activation score calculation\" paragraph 2", "quote": "“GSVA, v.3.5” was used to evaluate the activation status of 122 pathways, and for each sample in the TCGA-KIRC cohort, the enrichment score for a specific gene set was calculated to quantify the condition of total gene set activation [25]. 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CKS2 siRNA in renal cancer cells caused reductions in c", "tures of the three cohorts. Cell culture and transfection The 786-O cell line was obtained from the Am", "°C in a humidified 5 % CO2 incubator. 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