Department of Hematology-Oncology, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Nursing, Meiho University, Pingtung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Biomed J. 2022 Jun;45(3):522-532. doi: 10.1016/j.bj.2021.05.004. Epub 2021 May 19.
Stromal cell-derived factor-1α (SDF-1α) is a chemokine associated with tumor progression in various types of cancers. The current study aimed to evaluate whether pre-treatment or kinetics of SDF-1α can predict the prognosis in patients with esophageal squamous cell carcinoma (ESCC) receiving definitive concurrent chemoradiotherapy (CCRT).
A total of 97 patients with ESCC were identified at Kaohsiung Chang Gung Memorial Hospital between January 2010 and December 2015. Serum concentration of SDF-1α was measured at day 0 (pre-treatment) and chemotherapy day 28 to determine its kinetics and the cut-off level of pre-chemotherapy SDF-1α was 1.5 ng/mL. Two ESCC cell lines, TE1 and KYSE30, were selected to evaluate the function of SDF-1α.
Univariate and multivariate analyses showed that pre-treatment SDF-1α ≥ 1.5 ng/mL and an increased SDF-1α level after treatment were significantly associated with worse progression-free survival (p = 0.021 and p = 0.008, respectively) and overall survival (p = 0.005 and p < 0.001, respectively). In addition, patients with pre-treatment SDF-1α ≥ 1.5 ng/mL and increased SDF-1α levels after treatment were found to have poor response to CCRT. Moreover, these cell lines were treated with chemotherapeutic agents (cisplatin or 5-FU) and SDF-1α, alone or in combination. Our in vitro study results showed SDF-1α promoted the proliferation of tumor cells and overcame the cytotoxic effect of chemotherapy (p < 0.001).
Our study suggested that SDF-1α plays an important role in ESCC disease progression and that pre-treatment SDF-1α level and kinetics of SDF-1α are the independent prognostic factors for ESCC patients receiving definitive CCRT. Periodic determinations of serum SDF-1α level may be valuable to predict prognosis of ESCC in clinical practice.
基质细胞衍生因子-1α（SDF-1α）是一种与多种癌症肿瘤进展相关的趋化因子。本研究旨在评估 SDF-1α 的预处理或动力学是否可以预测接受根治性同期放化疗（CCRT）的食管鳞状细胞癌（ESCC）患者的预后。
在 2010 年 1 月至 2015 年 12 月期间，在高雄长庚纪念医院共确定了 97 名 ESCC 患者。在第 0 天（预处理）和化疗第 28 天测量血清 SDF-1α 浓度以确定其动力学，并且预处理 SDF-1α 的截止值为 1.5ng/mL。选择 TE1 和 KYSE30 两种 ESCC 细胞系来评估 SDF-1α 的功能。
单因素和多因素分析表明，预处理 SDF-1α≥1.5ng/mL 和治疗后 SDF-1α 水平升高与无进展生存期（p=0.021 和 p=0.008）和总生存期（p=0.005 和 p<0.001）的更差显著相关。此外，预处理 SDF-1α≥1.5ng/mL 且治疗后 SDF-1α 水平升高的患者对 CCRT 反应不良。此外，用化疗药物（顺铂或 5-FU）和 SDF-1α 单独或联合处理这些细胞系。我们的体外研究结果表明，SDF-1α 促进了肿瘤细胞的增殖并克服了化疗的细胞毒性作用（p<0.001）。
我们的研究表明，SDF-1α 在 ESCC 疾病进展中起重要作用，预处理 SDF-1α 水平和 SDF-1α 动力学是接受根治性 CCRT 的 ESCC 患者的独立预后因素。定期测定血清 SDF-1α 水平可能对预测 ESCC 的临床预后有价值。
