Predictive value of EGF and uPAR for chemoradiotherapy response and survival in patients with esophageal squamous cell carcinoma.
Predictive value of EGF and uPAR for chemoradiotherapy response and survival in patients with esophageal squamous cell carcinoma.
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EGF和uPAR对食管鳞癌患者放化疗反应和生存的预测价值
DOI：
10.21037/atm-20-4503
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发表时间：
2020-09
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Chen X;Wei H;Qian D;Wang Y;Guan Y;Er P;Song Y;Liu N;Wang J;Zhao L;Yuan Z;Wang P;Pang Q;Zhang W
背景：放化疗(CRT)在食管鳞癌(ESCC)的治疗中占有重要地位。然而，还没有找到有效的生物标志物来预测ESCC患者CRT的敏感性和预后。本研究旨在检测68例ESCC患者表皮生长因子(EGF)和尿激酶型纤溶酶原激活物受体(UPAR)的细胞因子谱，并评价其临床应用价值。方法这项先导性研究纳入了68名患者，他们在2015-2017年间接受了新辅助CRT，随后接受了根治性手术或最终的CRT。每个患者在治疗前和总剂量40Gy时采集血清标本。使用包含120个已知肿瘤相关细胞因子的人细胞因子抗体阵列，对治疗前后血清中细胞因子的表达进行分析。结果4例CRT敏感和4例CRT耐药患者治疗前后血清细胞因子抗体阵列检测到7种差异表达的细胞因子。其中，40GyEGF和uPAR在血清中的上调与不良的临床结果相关。在第二组60例食管癌中进一步评估了EGF和uPAR的预测价值。共有68名患者参加了这项研究。中位随访期为15.87个月(6.21~23.85个月)。COX多因素生存分析显示，放疗后uPAR升高独立预测无进展生存率(PR)(HR=3.999，95%CI：1.503~10.639，P=0.006)，放疗后EGF值升高的患者总体生存率(OS)显著降低(HR=2.574，95%CI：1.046~6.335，P=0.040)。治疗前后血清uPAR表达与表皮生长因子表达呈显著正相关(P=0.0001，P=0.0038)。高表皮生长因子和uPAR比值的患者较高表皮生长因子比值、仅uPAR比值和无高表皮生长因子比值的患者的PFS和OS更差(1年PFS率44.2%对61.4%，1年OS率64.2%对83.4%，P=0.033和0.029)。结论血清EGF和uPAR水平是预测ESCC患者生存的可靠指标。有必要在更大的独立队列中进行进一步的前瞻性验证，以充分评估其预测能力。我们根据备注报告清单提交以下文章。
Background Chemoradiotherapy (CRT) plays a central role in the treatment of esophageal squamous cell carcinoma (ESCC). However, no effective biomarkers have been identified for predict CRT sensitivity and prognosis of patients with ESCC. The aim of this study was to investigate cytokine profiles of epidermal growth factor (EGF) and urokinase plasminogen activator receptor (uPAR) in 68 ESCC patients, and to evaluate the clinical utility of these markers. Methods This pilot study enrolled 68 patients who received neoadjuvant CRT followed by radical surgery or definitive CRT between 2015 and 2017. Serum specimen was obtained from each patient before treatment and at the time of administration of total doses of 40 Gy. Cytokines expression analyses were performed in pre- and post-treatment serum using human cytokine antibody arrays which contained 120 known tumor-related cytokines. Results Seven differentially expressed cytokines identified by cytokine antibody arrays in pre- and post-treatment serum from 4 patients with CRT sensitivity and 4 patients with CRT resistance. Of these, up-regulation of EGF and uPAR in serum at the doses of 40 Gy were associated with adverse clinical outcomes. The predictive value of EGF and uPAR were further assessed in a second set of 60 ESCCs. A total of 68 patients enrolled in this study. The median follow-up duration of these patients was 15.87 months (range, 6.21–23.85 months). Cox multivariate survival analyses revealed that high uPAR ratio after CRT independently predicted progression-free survival (PFS) (HR =3.999, 95% CI: 1.503–10.639, P=0.006) and patients with elevated levels of EGF after CRT exhibited significantly worse overall survival (OS) (HR =2.574, 95% CI: 1.046–6.335, P=0.040). Of note, uPAR expression was significantly positive correlation with EGF expression in pre- and post-treatment serum (P=0.0001, P=0.0038). Patients with both high EGF and uPAR ratios had an inferior PFS and OS, compared to patients with a high EGF ratio only or uPAR ratio only or neither (1-year PFS rate 44.2% vs. 61.4%, 1-year OS rate 64.2% vs. 83.4%, P=0.033 and 0.029, respectively). Conclusions The levels of EGF and uPAR in serum are reliable and predictive biomarkers for survival in ESCC patients. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power. We present the following article in accordance with the REMARK reporting checklist.
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影响因子：
51.1
作者：
Noordman, Bo Jan;Spaander, Manon C. W.;van Lanschot, J. Jan B.
通讯作者：
van Lanschot, J. Jan B.
影响因子：
2.7
作者：
Andres, Sarah A.;Edwards, Angelena B.;Wittliff, James L.
通讯作者：
Wittliff, James L.
影响因子：
--
作者：
Liu, Jinzhong;Li, Zhenfeng;Cui, Guanglin
通讯作者：
Cui, Guanglin
影响因子：
4.8
作者：
Duriseti, Sai;Goetz, David H.;Craik, Charles S.
通讯作者：
Craik, Charles S.
影响因子：
5
作者：
Ackland, ML;Newgreen, DF;Thompson, EW
通讯作者：
Thompson, EW