临床上有需要鉴定PSA升高的患者，以便于通过临床存在有临床意义的前列腺癌（CSCaP）来受益于前列腺活检。我们曾先前报告了适用于有临床意义的前列腺癌的MiCheck®测试的开发情况。在此，我们报告了MiCheck的进一步发展以及对罗氏全自动生化分析仪的整合。进一步开发和改良MiCheck®前列腺测试，使其能够在标准临床化学分析仪上使用，并使用MiCheck-01临床试验样本集来评估其性能。MiCheck-01美国临床试验中的大约358个患者样本被用于MiCheck®前列腺测试的开发。其中包括46个对照组，137个非前列腺癌（non-CaP），62个非临床意义前列腺癌（non-CSCaP）和113个临床意义前列腺癌。使用定制的Luminex基于R&D Systems多分析物测试套件来确定细胞生长因子的血清分析物浓度。研究了那些同样可以使用标准化学分析仪来测量的分析物，以评估它们对具有高敏感性的临床意义前列腺癌检测算法的贡献能力。然后使用罗氏全自动生化分析仪重新测量样本以开发最终算法。使用Monte Carlo交叉验证进行逻辑回归建模发现人附睾蛋白4（HE4）是一个能够显著提高算法特异性（在95%敏感性下）的分析物。使用来自Cobas分析仪的分析物测量开发了最终模型。MiCheck®逻辑回归模型包括PSA，％游离PSA，DRE和HE4。该模型能够将临床意义癌区分为无癌或非临床意义癌，AUC为0.85，敏感性为95％，特异性为50％。将MiCheck®测试应用于MiCheck-01研究中的所有可评估的358名患者，结果显示可以避免高达50%的不必要的活检，同时仅推迟了5.3%的Gleason评分（GS）≥3+4的癌症和1.8％的GS≥4+3的癌症，并没有延迟GS 8到10的癌症的诊断。MiCheck®前列腺测试具有很高的敏感性和阴性预测值（NPV）来鉴定临床意义前列腺癌。它可以在临床实验室中使用罗氏全自动生化分析仪进行测试。MiCheck®前列腺测试有助于减少不必要的前列腺活检，而只有极少数患者会延迟病症诊断。 © 2023 Elsevier Inc. 版权所有。

There is a clinical need to identify patients with an elevated PSA who would benefit from prostate biopsy due to the presence of clinically significant prostate cancer (CSCaP). We have previously reported the development of the MiCheck® Test for clinically significant prostate cancer. Here, we report MiCheck's further development and incorporation of the Roche Cobas standard clinical chemistry analyzer.To further develop and adapt the MiCheck® Prostate test so it can be performed using a standard clinical chemistry analyzer and characterize its performance using the MiCheck-01 clinical trial sample set.About 358 patient samples from the MiCheck-01 US clinical trial were used for the development of the MiCheck® Prostate test. These consisted of 46 controls, 137 non-CaP, 62 non-CSCaP, and 113 CSCaP.Serum analyte concentrations for cellular growth factors were determined using custom-made Luminex-based R&D Systems multi-analyte kits. Analytes that can also be measured using standard chemistry analyzers were examined for their ability to contribute to an algorithm with high sensitivity for the detection of clinically significant prostate cancer. Samples were then re-measured using a Roche Cobas analyzer for development of the final algorithm.Logistic regression modeling with Monte Carlo cross-validation was used to identify Human Epidydimal Protein 4 (HE4) as an analyte able to significantly improve the algorithm specificity at 95% sensitivity. A final model was developed using analyte measurements from the Cobas analzyer.The MiCheck® logistic regression model was developed and consisted of PSA, %free PSA, DRE, and HE4. The model differentiated clinically significant cancer from no cancer or not-clinically significant cancer with AUC of 0.85, sensitivity of 95%, and specificity of 50%. Applying the MiCheck® test to all evaluable 358 patients from the MiCheck-01 study demonstrated that up to 50% of unnecessary biopsies could be avoided while delaying diagnosis of only 5.3% of Gleason Score (GS) ≥3+4 cancers, 1.8% of GS≥4+3 cancers and no cancers of GS 8 to 10.The MiCheck® Prostate test identifies clinically significant prostate cancer with high sensitivity and negative predictive value (NPV). It can be performed in a clinical laboratory using a Roche Cobas clinical chemistry analyzer. The MiCheck® Prostate test could assist in reducing unnecessary prostate biopsies with a marginal number of patients experiencing a delayed diagnosis.Copyright © 2023 Elsevier Inc. All rights reserved.