An Wenxin, Zhao Chengyi, Wang Yaru, Zhang Yinghui, Qiao Zhi
Department of Urology, Harbin Medical University Cancer Hospital, 150 HaPing Road, NanGang, Harbin, 150081, Heilongjiang, China.
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Discov Oncol. 2024 Nov 4;15(1):617. doi: 10.1007/s12672-024-01493-0.
Blood and urine biomarkers have been associated with urologic tumors, but their causal relationship with urologic tumors is unclear.
We performed a bidirectional Mendelian randomization (MR) analysis of the association between 35 blood and urine biomarkers and urological tumors in our discovery cohort. A Bayesian weighting approach was used to validate the positive results identified in the discovery cohort, and steiger filtering analysis was used to distinguish causality from reverse causality. Bayesian colocalization analysis was used to analyze which single nucleotide polymorphisms (SNPs) specifically co-located between the positive blood and urine biomarkers and the disease phenotypes were driven, and MR-positive results from the discovery cohort and the validation cohort were combined using the MR-meta method.
Several blood and urine biomarkers were found to be significantly and causally associated with urologic cancers. Notably, calcium (OR: 1.34, 95%CI 1.10-1.63, P = 0.0040) and sex hormone-binding globulin (SHBG) (OR: 0.81, 95%CI 0.70-0.95, P = 0.0092) were associated with bladder cancer; gamma glutamyl transferase (GGT) (OR: 0.91, 95%CI 0.83-0.99, P = 0.0209), lipoprotein A (Lp(a)) (OR: 1.12, 95%CI 1.01-1.24, P = 0.0399), and insulinlike growth factor 1 (IGF 1) (OR: 1.10, 95%CI 1.01-1.20, P = 0.0220) were linked to prostate cancer (PCa); non albumin protein (OR: 0.78, 95%CI 0.65-0.93, P = 0.0065) and total protein (OR: 0.80, 95%CI 0.64-0.99, P = 0.0380) were linked to renal cancer; and apolipoprotein A (Apo-A) (OR: 0.56, 95%CI 0.32-0.98, P = 0.0426) and urate (OR:1.89, 95%CI 1.03-3.47, P = 0.0399) were associated with renal pelvis cancer. These associations were validated in an independent cohort, with GGT, IGF 1, and Lp(a) being consistently linked to PCa.
This study identified significant biomarkers associated with urological cancers in blood and urine. These include GGT, IGF 1, and Lp(a), which are strong biomarkers for PCa. In addition, the findings of this study provide evidence for a handful of risk and protective factors for the development of urologic cancers.
血液和尿液生物标志物已被证明与泌尿系统肿瘤有关，但其与泌尿系统肿瘤之间的因果关系尚不清楚。
我们在发现队列中对35种血液和尿液生物标志物与泌尿系统肿瘤之间的关联进行了双向孟德尔随机化（MR）分析。采用贝叶斯加权方法对在发现队列中确定的阳性结果进行验证，并使用斯泰格过滤分析来区分因果关系和反向因果关系。贝叶斯共定位分析用于分析哪些单核苷酸多态性（SNP）在阳性血液和尿液生物标志物与疾病表型之间特异性共定位，并使用MR-meta方法将发现队列和验证队列中的MR阳性结果合并。
发现几种血液和尿液生物标志物与泌尿系统癌症存在显著的因果关系。值得注意的是，钙（OR：1.34，95%CI 1.10-1.63，P = 0.0040）和性激素结合球蛋白（SHBG）（OR：0.81，95%CI 0.70-0.95，P = 0.0092）与膀胱癌有关；γ-谷氨酰转移酶（GGT）（OR：0.91，95%CI 0.83-0.99，P = 0.0209）、脂蛋白A（Lp(a)）（OR：1.12，95%CI 1.01-1.24，P = 0.0399）和胰岛素样生长因子1（IGF 1）（OR：1.10，95%CI 1.01-1.20，P = 0.0220）与前列腺癌（PCa）有关；非白蛋白蛋白（OR：0.78，95%CI 0.65-0.93，P = 0.0065）和总蛋白（OR：0.80，95%CI 0.64-0.99，P = 0.0380）与肾癌有关；载脂蛋白A（Apo-A）（OR：0.56，95%CI 0.32-0.98，P = 0.0426）和尿酸（OR：1.89，95%CI 1.03-3.47，P = 0.0399）与肾盂癌有关。这些关联在独立队列中得到验证，其中GGT、IGF 1和Lp(a)始终与PCa相关。
本研究确定了血液和尿液中与泌尿系统癌症相关的重要生物标志物。这些包括GGT、IGF 1和Lp(a)，它们是PCa的强生物标志物。此外，本研究的结果为泌尿系统癌症发生的一些风险和保护因素提供了证据。
