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

Cancer Chemother Pharmacol. 2019 Apr;83(4):639-647. doi: 10.1007/s00280-019-03769-7. Epub 2019 Jan 14.

Abstract

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.

Keywords: Class III β-tubulin; Esophageal carcinoma; Nab-paclitaxel; Neoadjuvant chemotherapy; Secreted protein acidic and rich in cysteine.

MeSH terms

  • Aged
  • Albumins / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • 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
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Osteonectin / genetics*
  • Paclitaxel / administration & dosage
  • Prognosis
  • Prospective Studies
  • Survival Rate
  • Treatment Outcome
  • Tubulin / genetics*

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Osteonectin
  • SPARC protein, human
  • TUBB3 protein, human
  • Tubulin
  • Paclitaxel
  • Cisplatin