4.7 Article

RPN2 expression predicts response to docetaxel in oesophageal squamous cell carcinoma

Journal

BRITISH JOURNAL OF CANCER
Volume 107, Issue 8, Pages 1233-1238

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2012.396

Keywords

docetaxel; neoadjuvant chemotherapy; ESCC; RPN2; predictive marker

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Funding

  1. Japan Society for the Promotion of Science (JSPS) [23791550]
  2. Takeda Science Foundation
  3. Okukubo Memorial Fund for Medical Research in Kumamoto University School of Medicine
  4. Uehara Memorial Foundation
  5. Yokoyama Foundation for Clinical Pharmacology
  6. Grants-in-Aid for Scientific Research [23791550] Funding Source: KAKEN

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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. British Journal of Cancer (2012) 107, 1233-1238. doi:10.1038/bjc.2012.396 www.bjcancer.com Published online 6 September 2012 (C) 2012 Cancer Research UK

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