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RPN2 is effective biomarker to predict the outcome of combined chemotherapy docetaxel and cisplatin for advanced gastric cancer

Preoperative chemotherapy, often using docetaxel and cisplatin, is a famous treatment option for advanced gastric cancer in Japan. But, there are no effective biomarkers that predict the therapeutic outcome on gastric cancer. Ribophorin II (RPN2) silencing, which decreases glycosylation of P-glycoprotein (P-gp) and membrane localization, restores the sensitivity to docetaxel and cisplatin. We inquired whether RPN2 expression in advanced gastric cancer biopsy tissues may be a predictive biomarker for docetaxel and cisplatin combination preoperative chemotherapy. We judged RPN2 expression immunohistochemically in upper endoscopic biopsy tissues from 40 advanced gastric cancer patients, who received the combination preoperative chemotherapy of docetaxel and cisplatin and gastrectomy with D2 resection during 2008-2014, and compared clinicopathological effects between RPN2-positive and RPN2-negative groups. We also examined sensitivity of RPN2-knockout gastric cancer cells by genome editing to docetaxel and cisplatin. RPN2 expression was observed in 19 of 40 gastric cancer cases. The RPN2-negative group had better clinicopathological responses to docetaxel and cisplatin combination chemotherapy than the RPN2-positive group, especially, in assessment of the histopathological criteria to preoperative chemotherapy. And RPN2-negative group had a significantly higher overall survival and progression-free survival compared to the RPN2-positive group. We also found RPN2-knockout to change docetaxel and cisplatin sensitivity in vitro. RPN2 expression in upper endoscopic biopsy tissues can be an effective predictive biomarker for the treatment outcome to docetaxel and cisplatin combination preoperative chemotherapy in advanced gastric cancer.