分析 SPARC 和 TUBB3 作为接受 nab-紫杉醇加顺铂新辅助化疗的食管鳞癌患者预后的预测因子:一项前瞻性研究。
Analysis of SPARC and TUBB3 as predictors for prognosis in esophageal squamous cell carcinoma receiving nab-paclitaxel plus cisplatin neoadjuvant chemotherapy: a prospective study.
机构信息
Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.
Zhejiang Key laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.
出版信息
Cancer Chemother Pharmacol. 2019 Apr;83(4):639-647. doi: 10.1007/s00280-019-03769-7. Epub 2019 Jan 14.
PURPOSE
The purpose of the study is to evaluate the predictive efficacy of secreted protein, acidic and rich in cysteine (SPARC) and the class III β-tubulin (β-tubulin III, TUBB3) in predicting therapeutic effect in patients with locally advanced esophageal squamous cell carcinoma(ESCC) who received nab-paclitaxel plus cisplatin neoadjuvant chemotherapy(CT) followed by surgery.
METHODS
Patients with stage II to III esophageal squamous cell carcinoma of different stages are recruited. The tumor biopsy tissues prior treatment from enrolled patients were examined by SPARC and TUBB3 immunohistochemistry (IHC). Correlations between SPARC/TUBB3 expression and response to chemotherapy and long-term survival in patients received surgical resection was analyzed.
RESULTS
A total of 35 patients with stage II to III esophageal squamous cell carcinoma were enrolled. Of the 35 enrolled patients, 30 successfully completed neoadjuvant chemotherapy and underwent R0 resection, 3 refused surgery after chemotherapy, and 2 failed to undergo radical surgery after chemotherapy. Out of patients undergoing surgery, pathological complete response (pCR) was achieved in 6 patients (6/30, 20%). The 1, 2 and 5-year disease free survival (DFS) rates were 70.0%, 36.6% and 33.3%, respectively. The 1, 2 and 5-year overall survival (OS) rates were 83.3%, 63.3% and 36.6%, respectively. SPARC and TUBB3 IHC was performed on the tumor biopsy tissues which were obtained from patients before treatment. Correlation between SPARC/TUBB3 expression and long-term survival in patients was studied. Both the median DFS and OS between SPARC negative samples and SPARC positive staining samples have no statistical difference. However, the median DFS and OS in TUBB3 negative patients was better than those in TUBB3 positive patients (p = 0.002 for DFS, p = 0.001 for OS). In addition, patients with pCR had longer OS and DFS time than those without pCR.COX regression analysis showed that TUBB3 prior treatment and pCR were independent prognostic factors in ESCC patients undergoing sequential surgery after preoperative chemotherapy.
CONCLUSIONS
TUBB3 negative expression prior treatment and pCR may indicate a better prognosis for stage II and III ESCC patients after nab-paclitaxel plus cisplatin neoadjuvant chemotherapy following radical esophagectomy.
目的
本研究旨在评估分泌型富含天冬氨酸和半胱氨酸的蛋白(SPARC)和 III 类β-微管蛋白(β-tubulin III,TUBB3)在接受 Nab-紫杉醇联合顺铂新辅助化疗(CT)后行手术治疗的局部晚期食管鳞状细胞癌(ESCC)患者中的预测疗效。
方法
招募不同分期的 II 期至 III 期食管鳞状细胞癌患者。对入组患者的肿瘤活检组织进行 SPARC 和 TUBB3 免疫组化(IHC)检查。分析 SPARC/TUBB3 表达与接受手术切除的患者化疗反应和长期生存之间的关系。
结果
共纳入 35 例 II 期至 III 期食管鳞状细胞癌患者。35 例入组患者中,30 例成功完成新辅助化疗并接受 RO 切除术,3 例化疗后拒绝手术,2 例化疗后无法行根治性手术。行手术的患者中,6 例(6/30,20%)达到病理完全缓解(pCR)。1、2 和 5 年无病生存率(DFS)分别为 70.0%、36.6%和 33.3%。1、2 和 5 年总生存率(OS)分别为 83.3%、63.3%和 36.6%。对患者治疗前获得的肿瘤活检组织进行 SPARC 和 TUBB3 IHC 检测。研究了 SPARC/TUBB3 表达与患者长期生存的相关性。SPARC 阴性样本和 SPARC 阳性染色样本的中位 DFS 和 OS 均无统计学差异。然而,TUBB3 阴性患者的中位 DFS 和 OS 优于 TUBB3 阳性患者(DFS 时 p=0.002,OS 时 p=0.001)。此外,pCR 患者的 OS 和 DFS 时间长于无 pCR 患者。COX 回归分析显示,新辅助化疗后序贯手术治疗的 ESCC 患者中,TUBB3 术前治疗和 pCR 是独立的预后因素。
结论
nab-紫杉醇联合顺铂新辅助化疗联合根治性食管切除术后,TUBB3 阴性表达和 pCR 可能预示 II 期和 III 期 ESCC 患者预后较好。