School of Medical Science, University of Campinas, Campinas, São Paulo, Brazil.
Dante Pazzanese Institute of Cardiology, São Paulo, Brazil.
BMC Cancer. 2021 May 19;21(1):575. doi: 10.1186/s12885-021-08317-2.
No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin.
We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity.
MiR-3168 (p = 1.98 × 10), miR-4718 (p = 4.24 × 10), and miR-6125 (p = 6.60 × 10) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00-1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03-2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98-3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61-0.93) with sensitivity of 66.76 and specificity of 79.49.
We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.
目前尚无生物标志物可用于识别接受顺铂治疗的患者发生肾毒性的风险。
我们使用微 RNA (miRNA) 测序技术，对 12 例头颈部癌症患者在顺铂治疗后 5 天（D5）采集的血浆进行检测，这些患者的肾毒性（血清肌酐升高≥2 级）有或无。选择两组间差异最显著的 miRNA 进行定量分析，检测其在更大患者队列中的基线和 D5 水平。采用单变量逻辑回归计算比值比 (OR) 评估 miRNA 与肾毒性的相关性。使用受试者工作特征曲线 (ROC) 评估曲线下面积 (AUC)、灵敏度和特异性。
miR-3168(p=1.98×10)、miR-4718(p=4.24×10)和 miR-6125(p=6.60×10)是差异最显著的 miRNA，进一步在 43、48 和 53 例患者中定量分析。miR-3168 的基线表达（p=0.0456，OR=1.03，95%CI：1.00-1.06）和 miR-4718（p=0.0388，OR=1.56，95%CI：1.03-2.46）与肾毒性风险增加相关，而 miR-6125 则呈趋势相关（p=0.0618，OR=1.73，95%CI：0.98-3.29）。miR-4718 的 AUC 最高（0.77，95%CI：0.61-0.93），灵敏度为 66.76%，特异性为 79.49%。
本研究为 miR-3168、miR-6125 和 miR-4718 的基线血浆表达作为顺铂诱导肾毒性的潜在预测因子提供了证据。
