Class III β-tubulin is a predictive marker for taxane-based chemotherapy in recurrent and metastatic gastric cancer

BMC Cancer. 2013 Sep 23:13:431. doi: 10.1186/1471-2407-13-431.

Abstract

Background: Class III β-tubulin (TUBB3) is a prognostic marker in various tumors, but the role of TUBB3 in advanced gastric cancer is not clearly defined. We analyzed the significance of TUBB3 expression, along with that of excision repair cross-complementation group 1 (ERCC1) in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy.

Methods: We reviewed the cases of 146 patients with advanced gastric adenocarcinoma who received taxane-based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun Hospital (Gwangju, Korea). Immunohistochemical staining for TUBB3 and ERCC1 was performed using paraffin wax-embedded tumor tissues. We evaluated the patients' response to chemotherapy, progression-free survival (PFS), and overall survival (OS).

Results: In total, 146 patients with advanced gastric cancer received docetaxel and cisplatin (n = 15) or paclitaxel and cisplatin (n = 131). The median PFS was significantly shorter for patients with high-level TUBB3 expression than for patients with low-level TUBB3 expression (3.63 vs. 6.67 months, P = 0.001). OS was not associated with TUBB3 expression (13.1 vs. 13.1 months, P = 0.769). By multivariate analysis, only TUBB3 was related to a shorter PFS (HR 2.74, 95% CI 1.91-3.91, P = 0.001). Patients with high-level ERCC1 expression showed a lower response rate than patients with low-level ERCC1 expression (24 vs. 63.2%, P = 0.001); however, ERCC1 had no clinical effect on PFS or OS.

Conclusions: TUBB3 was a strong predictive marker in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. No clinical impact of ERCC1 was evident in this setting.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor*
  • Bridged-Ring Compounds / administration & dosage
  • DNA-Binding Proteins / metabolism
  • Endonucleases / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Prognosis
  • Recurrence
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Tubulin / metabolism*

Substances

  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • DNA-Binding Proteins
  • TUBB3 protein, human
  • Taxoids
  • Tubulin
  • taxane
  • ERCC1 protein, human
  • Endonucleases