Analysis of SPARC and TUBB3 as predictors for prognosis in esophageal squamous cell carcinoma receiving nab-paclitaxel plus cisplatin neoadjuvant chemotherapy: a prospective study

• Published in: Cancer chemotherapy and pharmacology 2019-04, Vol.83 (4), p.639-647
• Main Authors: Gong, Lei, Mao, Weimin, Chen, Qixun, Jiang, Youhua, Fan, Yun
• Format: Article
• Language: English
• Subjects: Aged; Albumins - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biopsy; Cancer Research; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Disease-Free Survival; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - pathology; Esophageal Squamous Cell Carcinoma - therapy; Esophagectomy; Esophagus; Female; Humans; Immunohistochemistry; Male; Median (statistics); Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oncology; Original Article; Osteonectin; Osteonectin - genetics; Paclitaxel; Paclitaxel - administration & dosage; Patients; Pharmacology/Toxicology; Prognosis; Prospective Studies; Proteins; Regression analysis; Squamous cell carcinoma; Statistical analysis; Statistical methods; Surgery; Survival; Survival Rate; Tissues; Treatment Outcome; Tubulin; Tubulin - genetics; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-019-03769-7

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.