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血浆硫代巴比妥酸反应性物质可预测初治转移性尿路上皮癌患者的生存率。

Plasma thiobarbituric acid reactive substances predicts survival in chemotherapy naïve patients with metastatic urothelial carcinoma.

作者信息

Slopovsky Jan, Kucharska Jarmila, Obertova Jana, Mego Michal, Kalavska Katarina, Cingelova Silvia, Svetlovska Daniela, Gvozdjakova Anna, Furka Samuel, Palacka Patrik

机构信息

2(nd) Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia; National Cancer Institute, Bratislava, Slovakia.

Pharmacobiochemical Laboratory of the 3(rd) Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.

出版信息

Transl Oncol. 2021 Jan;14(1):100890. doi: 10.1016/j.tranon.2020.100890. Epub 2020 Oct 12.

Abstract

Oxidative stress plays a significant role in development and progression of cancer, including urothelial carcinomas. TBARS (Thiobarbituric acid reactive substances) represents a marker of oxidative stress increased in various diseases. In this prospective study, we tested the hypothesis of plasma TBARS concentration and correlation with survival in chemotherapy naïve MUC (metastatic urothelial carcinoma) patients. Most of subjects (N = 65) were treated with gemcitabine and cisplatin (GC) chemotherapy. Performance status ECOG ≥2 had 11 patients, visceral metastases were present in 43. Based upon the mean of plasma TBARS, subjects were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared by log-rank test. At median follow-up of 9.6 months, 65 patients experienced progression and 64 died. Subjects with low TBARS had significantly better PFS (HR 0.51) and OS (HR 0.44) opposed to high TBARS. Patients with low TBARS had significantly higher rate of neutropenia G4 and less liver involvement. High TBARS correlated with BMI above 30 kg/m. Performance status and plasma TBARS were proven to be independent predictors of PFS and OS. In this study, high TBARS in MUC patients were associated with poor survival, likely due to more aggressive disease activity as reflected in increased liver involvement. Therefore, this biomarker could be used in clinical practice for early identification of patients with worse prognosis, better patient stratification, and treatment decision making.

摘要

氧化应激在包括尿路上皮癌在内的癌症发生和发展过程中起着重要作用。硫代巴比妥酸反应性物质(TBARS)是各种疾病中氧化应激增加的一个标志物。在这项前瞻性研究中,我们检验了初治转移性尿路上皮癌(MUC)患者血浆TBARS浓度及其与生存率相关性的假设。大多数受试者(N = 65)接受了吉西他滨和顺铂(GC)化疗。美国东部肿瘤协作组(ECOG)体能状态≥2分的患者有11例,43例存在内脏转移。根据血浆TBARS的均值,将受试者分为低水平组和高水平组。采用Kaplan-Meier法估计无进展生存期(PFS)、总生存期(OS)及其95%置信区间,并通过对数秩检验进行比较。在中位随访9.6个月时,65例患者病情进展,64例死亡。与TBARS高水平的受试者相比,TBARS低水平的受试者PFS(风险比0.51)和OS(风险比0.44)明显更好。TBARS低水平的患者4级中性粒细胞减少的发生率明显更高,肝脏受累情况更少。TBARS高水平与体重指数高于30kg/m²相关。体能状态和血浆TBARS被证明是PFS和OS的独立预测因素。在本研究中,MUC患者TBARS高水平与较差的生存率相关,可能是由于肝脏受累增加所反映的疾病活动更具侵袭性。因此,这种生物标志物可用于临床实践,以早期识别预后较差的患者,更好地对患者进行分层,并做出治疗决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f930/7566937/0a6add188810/gr1.jpg

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