Creation of a primary tumor tissue expression biomarker-augmented prognostic model for patients with metastatic renal cell carcinoma.
Urol Oncol
; 39(2): 135.e1-135.e8, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33309297
ABSTRACT
BACKGROUND:
Clinical and pathological factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). Bim, a downstream pro-apoptotic molecule in the PD-1 signaling pathway, has recently been associated with survival in other malignancies. We sought to determine if tissue biomarkers including Bim, added to a previously reported clinical metastases score, improved prediction of cancer-specific survival (CSS) for patients with metastatic ccRCC.METHODS:
Patients with metastatic ccRCC who underwent nephrectomy between 1990 and 2004 were identified using our institutional registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for Bim, PD-1, B7-H1 (PD-L1), B7-H3, CA-IX, IMP3, Ki67, and survivin. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index.RESULTS:
The cohort included 602 patients 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up was 9.6 years (IQR 4.2-12.8), during which 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score, and were eligible for biomarker-specific model inclusion. After variable selection, high Bim (hazard ratio [HR]â¯=â¯1.44; 95% confidence interval [CI] 1.16-1.78; P <0.001), high survivin (HRâ¯=â¯1.35; 95% CI 1.08-1.68; Pâ¯=â¯0.008), and the metastases score (HRâ¯=â¯1.13 per 1 point; 95% CI 1.10-1.16; P <0.001) were retained in the final multivariable model (c-indexâ¯=â¯0.69).CONCLUSION:
We created a prognostic model combining the clinical metastases score and 2 primary tumor tissue expression biomarkers, Bim and survivin, for patients with metastatic renal cell carcinoma who underwent nephrectomy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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Biomarcadores Tumorais
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Proteína 11 Semelhante a Bcl-2
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Neoplasias Renais
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Urol Oncol
Assunto da revista:
NEOPLASIAS
/
UROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Mongólia