肾功能相关指标对晚期非小细胞肺癌患者预后的意义

The Prognostic Significance of Renal Function-Related Indicators in Advanced NSCLC Patients

摘要: 目的：本研究分析晚期非小细胞肺癌(NSCLC)患者初次接受抗肿瘤治疗前的尿酸(UA)、胱抑素C (CysC)与估算的肾小球滤过率(eGFR)水平和疾病进展时上述指标的水平，研究其预后价值。方法：从2014年11月至2022年5月，回顾性收集了青海大学附属医院153例患者的临床资料，并且经过病理确诊为NSCLC，收集其一线治疗前1周内的UA、CysC、eGFR基线水平，以及疾病进展时的UA、CysC、eGFR水平，通过查阅医院的病历系统、打电话等方法进行随访，取得患者的生存数据，包括无进展生存期(PFS)、总生存期(OS)，定义从患者一线治疗发生疾病进展时的时间开始至任何原因导致死亡的时间为OS₁，OS₁也为随访患者的生存数据之一。绘制受试者工作特征曲线(ROC)，根据UA、CysC、eGFR的最佳截断值，将患者分为高、低水平组。采用卡方检验评估高、低水平组患者与临床分类变量是否存在关联。应用Cox比例风险模型对相关参数进行单因素、多因素生存分析，使用Kaplan-Meier法绘制生存曲线，组间差异比较使用Log-rank检验；使用配对卡方检验检查UA、CysC、eGFR水平在治疗前和疾病进展时是否有变化；最后另收集23例患者的数据对所得出的结果进行验证。使用SPSS 27.0统计软件处理数据，各统计结果均以P < 0.05认为有统计学差异。结果：在治疗前：UA ≥ 292.50 umol/L、eGFR < 79.43 mL/min/1.73m²是患者预后的独立危险因素；在疾病进展时：eGFR < 79.43 mL/min/1.73m²是患者预后的独立危险因素；在治疗前：UA < 292.50 umol/L组患者的中位OS明显高于UA ≥ 292.50 umol/L组，两组间的患者生存率存在差异；eGFR < 79.43 mL/min/1.73m²组患者的中位OS明显低于eGFR ≥ 79.43 mL/min/1.73m²组，两组间的患者生存率存在差异；在疾病进展时：eGFR < 79.43 mL/min/1.73m²组患者的中位OS₁低于eGFR ≥ 79.43 mL/min/1.73m²组，两组间的患者生存率存在差异；联合检测治疗前UA、eGFR的水平将更有助于分层评估晚期NSCLC的预后；治疗前UA、CysC水平与患者的PFS相关，联合检测治疗前UA与CysC的水平有助于分层预测晚期NSCLC的疗效。结论：在治疗前：UA ≥ 292.50 umol/L、eGFR < 79.43 mL/min/1.73m²是患者预后的独立危险因素；在疾病进展时：eGFR < 79.43 mL/min/1.73m²是患者预后的独立危险因素；联合检测治疗前UA、eGFR的水平可能有助于分层评估晚期NSCLC的预后。

Abstract: Objective: In this study, uric acid (UA), cystatin C (CysC), estimated glomerular filtration rate (eGFR) levels, and the levels of the above indicators at the time of disease progression in patients with advanced non-small cell lung cancer (NSCLC) before initial antitumor therapy were analyzed, and their prognostic value was studied. Methods: From November 2014 to May 2022, clinical data of 153 patients who were pathologically diagnosed with NSCLC were retrospectively collected from Qinghai University Affiliated Hospital. The baseline levels of UA, CysC, and eGFR within 1 week before first-line treatment, as well as the levels at disease progression, were collected. Follow-up was conducted by reviewing the hospital’s medical record system and making phone calls to obtain patient survival data, including progression-free survival (PFS) and overall survival (OS). OS₁ was defined as the time from disease progression at first-line treatment to death from any cause and was also one of the survival data of the follow-up patients. Receiver operating characteristic (ROC) curves were drawn, and patients were divided into high- and low-level groups based on the optimal cutoff values of UA, CysC, and eGFR. The chi-square test was used to evaluate the association between high and low-level groups of patients and clinical classification variables. Cox proportional hazards models were used for univariate and multivariate survival analysis of relevant parameters. Kaplan-Meier curves were used to plot survival curves, and the Log-rank test was used to compare differences between groups. The paired chi-square test was used to examine whether UA, CysC, and eGFR levels changed before treatment and at disease progression. Finally, data from 23 additional patients were collected to validate the results. SPSS 27.0 statistical software was used to process the data, and all statistical results were considered significant at P < 0.05.Results: Before treatment: UA ≥ 292.50 umol/L and eGFR < 79.43 mL/min/1.73m² were independent risk factors for prognosis; At disease progression: eGFR < 79.43 mL/min/1.73m² is an independent risk factor for prognosis; Before treatment, the median OS of patients in the UA < 292.50 umol/L group was significantly higher than that in the UA ≥ 292.50 umol/L group, and there was a difference in survival between the two groups. The median OS of patients in the eGFR < 79.43 mL/min/1.73m² group was significantly lower than that in the eGFR ≥ 79.43 mL/min/1.73m² group, and there was a difference in survival between the two groups. At the time of disease progression: the median OS₁ in the eGFR < 79.43 mL/min/1.73m² group was lower than that in the eGFR ≥ 79.43 mL/min/1.73m² group, and there was a difference in survival between the two groups; Combined detection of the levels of UA and eGFR before treatment will be more helpful to stratified assessment of the prognosis of advanced NSCLC. The levels of pretreatment UA and CysC were related to PFS, and the combined detection of UA and CysC levels before treatment helped to stratified prediction of the efficacy of advanced NSCLC. Conclusions: Before treatment: UA ≥ 292.50 umol/L and eGFR < 79.43 mL/min/1.73m² were independent risk factors for prognosis; At disease progression: eGFR < 79.43 mL/min/1.73m² is an independent risk factor for prognosis; Combined testing of the levels of UA and eGFR before treatment will be more helpful in stratified assessment of the prognosis of advanced NSCLC.