Multicenter Validation of Enhancer of Zeste Homolog 2 Expression as an Independent Prognostic Marker in Localized Clear Cell Renal Cell Carcinoma
| العنوان: | Multicenter Validation of Enhancer of Zeste Homolog 2 Expression as an Independent Prognostic Marker in Localized Clear Cell Renal Cell Carcinoma |
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| المؤلفون: | Farrah Homayoun, Daniel J. Serie, Alexander S. Parker, Richard W. Joseph, Payal Kapur, Jeanette E. Eckel-Passow, Thai H. Ho, John C. Cheville, Vandana Panwar, Alana Christie, James Brugarolas, R. Houston Thompson |
| المصدر: | Journal of Clinical Oncology |
| بيانات النشر: | American Society of Clinical Oncology, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, macromolecular substances, Bioinformatics, 03 medical and health sciences, Necrosis, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Adjuvant therapy, Carcinoma, Biomarkers, Tumor, Humans, Enhancer of Zeste Homolog 2 Protein, Survival rate, Carcinoma, Renal Cell, Aged, Neoplasm Staging, Aged, 80 and over, business.industry, Proportional hazards model, EZH2, ORIGINAL REPORTS, Middle Aged, medicine.disease, Prognosis, Kidney Neoplasms, United States, 3. Good health, Clinical trial, Survival Rate, Clear cell renal cell carcinoma, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, Urologic Oncology, Female, Neoplasm Grading, business |
| الوصف: | Purpose Enhancer of zeste homolog 2 (EZH2), a chromatin remodeler, is implicated in the pathogenesis of clear cell renal cell carcinoma (ccRCC). However, the effect of EZH2 on outcomes in localized ccRCC is unclear, and molecular biomarkers are not currently integrated into prognostic models or adjuvant therapy trials. Methods We performed Cox regression to evaluate the association of tumor-based EZH2 gene and protein expression with survival in three independent cohorts: a cohort from The Cancer Genome Atlas (n = 532), a cohort from University of Texas Southwestern Medical Center (n = 122), and a cohort from Mayo Clinic (n = 1,338). Analyses were adjusted for the prognostic stage, size, grade, and necrosis (SSIGN) score as well as within low-, intermediate-, and high-risk SSIGN groups. Results Patients in The Cancer Genome Atlas cohort with EZH2-high gene expression were 1.5 times more likely to experience overall death than patients with EZH2-low expression (95% CI, 1.1 to 2.3; P = .028). Patients in the University of Texas Southwestern Medical Center cohort with EZH2-high protein expression were two times more likely to experience overall death than patients with EZH2-low expression (95% CI, 1.1 to 4.4; P = .034). Similarly, patients in the Mayo Clinic cohort with EZH2-high protein expression were 1.4 times more likely to experience overall death (95% CI, 1.2 to 1.7; P < .001). Patients in the Mayo Clinic cohort with EZH2-high protein expression were nearly two times more likely to experience RCC-specific death (95% CI, 1.5 to 2.6; P < .001); EZH2 protein expression was particularly prognostic among patients with low-risk SSIGN tumors (HR, 6.1; 95% CI, 3.4 to 11.1; P < .001). Conclusion EZH2 expression accurately predicts risk of RCC death beyond existing clinicopathologic models, particularly in low- and intermediate-risk SSIGN tumors. Further studies are required to incorporate molecular biomarkers into surveillance guidelines and adjuvant clinical trials. |
| اللغة: | English |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2133898ca098f77b7a8c7a1f6a629829Test http://europepmc.org/articles/PMC5678341Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2133898ca098f77b7a8c7a1f6a629829 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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