Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: A Laboratory Wide Association Study (LWAS).

Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: A Laboratory Wide Association Study (LWAS).
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DOI:
10.1016/j.urolonc.2021.08.011
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发表时间:
2022-01
影响因子:
2.7
通讯作者:
Leppert, John T.
Leppert, John T.
中科院分区:
医学3区
文献类型:
--
作者:
Velaer, Kyla;Thomas, I-Chun;Yang, Jaden;Kapphahn, Kristopher;Metzner, Thomas J.;Golla, Abhinav;Hoerner, Christian R.;Fan, Alice C.;Master, Viraj;Chertow, Glenn M.;Brooks, James D.;Patel, Chirag J.;Desai, Manisha;Leppert, John T.

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转移性肾细胞癌 (mRCC) 患者的预后模型包括选定的实验室值。这些模型具有重要的局限性,包括依赖有限的实验室测试,以及使用二分法(“高-低”)截止值。我们应用实验室范围关联研究 (LWAS) 框架来系统评估与诊断为转移性肾细胞癌 (mRCC) 患者的生存相关的常见临床实验室结果。我们使用了 2002 年至 2017 年诊断为转移性肾细胞癌 (mRCC) 的 3,385 名患者的实验室数据。我们开发了一个 LWAS 框架,以检查 53 项常见临床实验室测试结果(641,712 次测量)与总体生存率的关联。我们采用错误发现率来测试多项实验室测试与生存率的关联,并使用 3 个独立的队列验证这些结果,以生成标准化风险比 (sHR),报告每次实验室测试中 1 个标准差单位的变化。 LWAS 方法证实了目前用于预后模型的实验室值与生存的关联,包括钙(HR 1.35,95%CI 1.24–1.48)、白细胞计数(HR 1.40,95%CI 1.30–1.51)、血小板计数(HR 1.36,95%CI 1.27–1.51)和血红蛋白(HR 1.36,95%CI 1.27–1.51)。 0.79,95%CI 0.72–0.86)。使用这些测试作为连续变量可以提高模型性能。 LWAS 还鉴定了通常不包含在预后模型中的与生存相关的急性期反应物,包括血清白蛋白(HR 0.66,95%CI 0.61–0.72)、铁蛋白(HR 1.25,95%CI 1.08–1.45)、碱性磷酸酶(HR 1.31,95%CI 1.23–1.40)和 C 反应蛋白(HR 1.31,95%CI 1.23–1.40)。 1.70,95%CI 1.14–2.53)。常规测量的实验室测试可以完善当前的预后模型,促进临床试验队列之间的比较,并将患者与特定的系统疗法相匹配。由爱思唯尔公司出版
Prognostic models for patients with metastatic renal cell carcinoma (mRCC) include select laboratory values. These models have important limitations, including reliance on a limited array of laboratory tests, and use of dichotomous (“high-low”) cutoffs. We applied a Laboratory-Wide Association Study (LWAS) framework to systematically evaluate common clinical laboratory results associated with survival for patients diagnosed with mRCC. We used laboratory data for 3,385 patients diagnosed with mRCC from 2002 to 2017. We developed a LWAS framework, to examine the association with 53 common clinical laboratory tests results (641,712 measurements) and overall survival. We employed false-discovery rate to test the association of multiple laboratory tests with survival, and validated these results using 3 separate cohorts to generate a standardized hazard ratio (sHR), reported for a 1 standard deviation unit change in each laboratory test. The LWAS approach confirmed the association of laboratory values currently used in prognostic models with survival, including calcium (HR 1.35, 95%CI 1.24–1.48), leukocyte count (HR 1.40, 95%CI 1.30–1.51), platelet count (HR 1.36, 95%CI 1.27–1.51), and hemoglobin (HR 0.79, 95%CI 0.72–0.86). Use of these tests as continuous variables improved model performance. LWAS also identified acute phase reactants associated with survival not typically included in prognostic models, including serum albumin (HR 0.66, 95%CI 0.61–0.72), ferritin (HR 1.25, 95%CI 1.08–1.45), alkaline phosphatase (HR 1.31, 95%CI 1.23–1.40), and C-reactive protein (HR 1.70, 95%CI 1.14–2.53). Routinely measured laboratory tests can refine current prognostic models, facilitate comparisons across clinical trial cohorts, and match patients with specific systemic therapies. Published by Elsevier Inc.
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