title: Human antigen R as a predictive marker for response to gemcitabine-based chemotherapy in advanced cisplatin-resistant urothelial cancer.
abstract: In patients with advanced urothelial cancer (UC), a combination of cisplatin (CDDP) and gemcitabine (GEM) is the most commonly used first-line systematic chemotherapy regimen. Although no standard regime for the treatment of CDDP-resistant UC has been established, GEM-based regimens are frequently used in these patients. In other types of cancer, human antigen R (HuR) status in cancer cells is closely associated with patient response to GEM. The aim of the present study was to establish the predictive potential of HuR expression for disease progression and survival in patients with UC who were treated with GEM-based regimens as a first or second-line chemotherapy. A total of 50 patients with advanced UC were enrolled in the current study. As first-line chemotherapy, methotrexate, vinblastine, epirubicin and CDDP (MVEC) combination therapy and GEM and CDDP combination therapy were administered in 34 (68.0%) and 16 patients (32.0%), respectively. Following progression, 45 patients (90.0%) were treated with combined GEM and paclitaxel therapy, and 5 patients (10.0%) were treated with GEM monotherapy. Cytoplasmic and nuclear HuR expression was evaluated using immunohistochemical techniques. The associations between HuR expression levels and local tumor response and treatment outcomes were analyzed. In first-line chemotherapy, no anticancer effects were observed to be significantly associated with nuclear or cytoplasmic HuR expression. In second-line chemotherapy nuclear HuR expression also exhibited no significant association with anticancer effects; however, the local tumor response was significantly improved if positive cytoplasmic HuR expression was present (P=0.002). Multivariate analyses revealed that cytoplasmic HuR expression levels were a significant predictive marker for longer OS (hazard ratio, 0.22; 95% confidence interval, 0.09-0.56; P=0.001). No significant association was observed between nuclear HuR expression levels and the overall survival. Therefore, cytoplasmic HuR expression is a significant predictive marker of response to GEM-based chemotherapy in patients with CDDP-resistant UC. Despite the limitations of a small and retrospective study, the results of the present study may facilitate the development of novel treatment strategies and provide a focus for additional basic and clinical studies.
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Mitsunari
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Asai
authors.initials: A
authors.lastname: Akihiro
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Watanabe
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Ohba
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
keywords: gemcitabine; human antigen R; predictive marker; urothelial cancer