RPN2 expression predicts response to docetaxel in oesophageal squamous cell carcinoma

Br J Cancer. 2012 Oct 9;107(8):1233-8. doi: 10.1038/bjc.2012.396. Epub 2012 Sep 6.

Abstract

Background: Neoadjuvant chemotherapy - often using docetaxel in various combinatorial regimens - is a standard treatment choice for advanced oesophageal squamous cell carcinoma (ESCC) in Japan. However, no useful markers exist that predict docetaxel's effects on ESCC. Ribophorin II (RPN2) silencing, which reduces glycosylation of P-glycoproteins and decreases membrane localisation, promotes docetaxel-dependent apoptosis. We investigated whether RPN2 expression in ESCC biopsy specimens could be a predictive biomarker in docetaxel-based neoadjuvant chemotherapy.

Methods: We evaluated RPN2 expression immunohistochemically in biopsy specimens from 79 patients with node-positive ESCC, who received docetaxel-based adjuvant chemotherapy, and compared clinical and pathological responses between the RPN2-positive and RPN2-negative groups. We also studied susceptibility of RPN2-suppressed ESCC cells to docetaxel.

Results: The RPN2-negative group had better clinical and pathological responses to docetaxel than the RPN2-positive group. We also found RPN2 suppression to alter docetaxel susceptibility in vitro.

Conclusion: Expression of RPN2 in biopsy specimens could be a useful predictive marker for response to docetaxel-based neoadjuvant chemotherapy in ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / surgery
  • Docetaxel
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / surgery
  • Female
  • Hexosyltransferases
  • Humans
  • Male
  • Neoadjuvant Therapy
  • Proteasome Endopeptidase Complex / genetics*
  • Taxoids / administration & dosage*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Taxoids
  • Docetaxel
  • Hexosyltransferases
  • RPN2 protein, human
  • Proteasome Endopeptidase Complex