The prognostic significance of human equilibrative nucleoside transporter 1 expression in patients with metastatic bladder cancer treated with gemcitabine‐cisplatin‐based combination chemotherapy

Matsumura, Nagahide; Nakamura, Yasushi; Kohjimoto, Yasuo; Inagaki, Takeshi; Nanpo, Yoshihito; Yasuoka, Hironao; Ohashi, Yasuo; Hara, Isao

doi:10.1111/j.1464-410x.2010.09932.x

Cited by 34 publications

(32 citation statements)

References 24 publications

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“…Bellmunt et al (30) demonstrated that survival was significantly higher in individuals with low ERCC1 mRNA levels among 57 patients with advanced and metastatic bladder cancer treated with cisplatin-based chemotherapy. Matsumura et al (31) reported no significant differences in survival between high-and low-ERCC1 expression in 40 metastatic bladder cancer patients treated with gemcitabine-cisplatin-based combination chemotherapy. Hoffmann et al (32) indicated that high-ERCC1 mRNA expression was associated with inferior outcomes following cisplatin-based adjuvant chemotherapy in 108 patients with locally advanced bladder cancer.…”

Section: Discussionmentioning

confidence: 98%

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ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Sakano

Ogawa

Yamamoto

et al. 2013

Molecular and Clinical Oncology

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Abstract. Combined trimodality therapy, including transurethral resection and platinum-based chemoradiotherapy, has shown promising results for muscle-invasive bladder cancer. However, this type of treatment may decrease survival as a result of delayed cystectomy in patients with non-responding tumors. DNA repair proteins may affect survival of bladder cancer patients receiving combined trimodality therapy, by affecting the perioperative nature of the tumor cells or by repairing DNA damaged by platinum agents and radiation. We investigated the associations of excision repair cross-complementing group 1 (ERCC1), X-ray repair cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with response and survival in 157 locally advanced bladder cancer patients receiving combined trimodality therapy, in order to determine the predictive value of the expression of these proteins in patient selection for therapy. We examined ERCC1, XRCC1 and APE1 expression in tumor specimens using immunohistochemistry. Patients positive for ERCC1, positive for XRCC1 and positive for either ERCC1 or XRCC1, exhibited significantly improved disease-specific survival rates (P=0.023, 0.025 and 0.0091, respectively). In multivariate analysis, combined ERCC1 and XRCC1 expression was independently associated with disease-specific mortality [risk ratio (RR): 0.64; 95% confidence interval (CI), 0.43-0.94 and P=0.024]. Thus, combined ERCC1 and XRCC1 expression may serve as an independent prognostic marker for survival in bladder cancer patients receiving combined trimodality therapy. Prospective studies with a larger sample size are required to confirm these results.

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Section: Discussionmentioning

confidence: 98%

“…Previous studies investigated ERCC1 expression in bladder cancer treated with (chemo)radiation therapy (30)(31)(32)(33). Bellmunt et al (30) demonstrated that survival was significantly higher in individuals with low ERCC1 mRNA levels among 57 patients with advanced and metastatic bladder cancer treated with cisplatin-based chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Sakano

Ogawa

Yamamoto

et al. 2013

Molecular and Clinical Oncology

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“…In a clinical study using immunohistochemistry, Olaussen et al reported that patients with ERCC1-negative non-small-cell lung cancer appeared to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors did not (23). In a clinical study of bladder cancer, a number of studies addressed the correlation between ERCC1 and prognosis (14)(15)(16)(17). However, the role of ERCC1 in predicting the prognosis for advanced bladder cancer was controversial.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, we reported that ERCC1 may predict the prognosis of chemoradiotherapy for bladder cancer and that it was correlated with radiation rather than cisplatin resistance in an in vitro study (13). A correlation between ERCC1 and bladder cancer has been reported (14)(15)(16)(17), but whether ERCC1 is capable of predicting a favorable survival rate in patients with advanced bladder cancer treated with cisplatin-based chemotherapy is controversial.…”

Section: Introductionmentioning

confidence: 98%

Co-expression of ERCC1 and Snail is a prognostic but not predictive factor of cisplatin-based neoadjuvant chemotherapy for bladder cancer

et al. 2012

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Abstract. Neoadjuvant chemotherapy (NC) for bladder cancer has been reported to significantly improve the 5-year survival rate. The aim of the present study was to examine the roles of ERCC1 and Snail in determining the response to chemotherapy in bladder cancer treated with NC and radical cystectomy (RC). The expression of the Snail and ERCC1 proteins was determined by immunohistochemical staining of specimens obtained from 58 patients with bladder tumors treated with NC and RC. The correlation between clinical response and the expression of Snail and ERCC1 was investigated. Snail and ERCC1 were co-expressed in 24 (41.4%) of the 58 patients. A marked correlation was found between the expression of Snail and ERCC1 (P=0.001). The co-expression of Snail and ERCC1 was not able to predict pathological complete response (P=0.202). Results of the univariate analysis revealed that the co-expression of Snail and ERCC1 predicted shorter diseasefree survival (DFS) and overall survival (OS) than the negative expression of Snail and/or ERCC1. Moreover, the co-expression of ERCC1 and Snail was the only predictive factor for both DFS (P=0.029) and OS (P=0.040). The expression of Snail was correlated with that of ERCC1 and the co-expression of Snail and ERCC1 was the only significant predictive factor of shorter DFS and OS in patients with bladder cancer treated with NC and RC. IntroductionBladder cancer is the fourth most common cancer in males in the USA (1). For muscle-invasive bladder cancer, radical cystectomy (RC) and urinary diversion are the gold standard of therapy in many parts of the world (1-3). Neoadjuvant chemotherapy (NC) with cisplatin-based combination chemotherapy significantly improved the 5-year survival rate in two meta-analysis studies (4,5) and pathological complete response (pCR) with NC was correlated with survival (6,7). Although a number of studies have discussed factors which predict pCR or a favorable survival rate (8-10), none of the factors has been proven in a clinical study.The excision repair cross-complementing group 1 (ERCC1) gene is located on chromosome 19q13.2-q13.3. The ERCC1 protein is crucial in the nucleotide excision repair pathway (11,12). In a previous study, we reported that ERCC1 may predict the prognosis of chemoradiotherapy for bladder cancer and that it was correlated with radiation rather than cisplatin resistance in an in vitro study (13). A correlation between ERCC1 and bladder cancer has been reported (14-17), but whether ERCC1 is capable of predicting a favorable survival rate in patients with advanced bladder cancer treated with cisplatin-based chemotherapy is controversial.The endothelial-mesenchymal transition (EMT) is significant in invasive bladder cancer (18,19). Mesenchymal markers, including N-cadherin, Zeb1, Snail and Slug, suppress the expression of E-cadherin and are correlated with radiation and cisplatin resistance in numerous types of cancer (20)(21)(22). In their study, Hsu et al reported that Snail regulated the expression of ERCC1 and that the co-expressi...

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“…Since the majority of patients with mCRC ultimately die of the disease, predictive biomarkers are particularly important. Expression profiles of hENT have been assessed in a variety of cancers, including gastrointestinal, breast, biliary tract, pancreatic, bladder, and lung cancers, and shown to have predictive value for the efficacy of nucleoside-derived drugs (Achiwa et al, 2004;Giovannetti et al, 2006;Molina-Arcas et al, 2006;Oguri et al, 2007;Kameyama et al, 2011;Matsumura et al, 2011;Santini et al, 2008Santini et al, , 2011Ormanns et al, 2014). Gemcitabine is a drug that requires active transport into the cell by hENT1 to function therapeutically (Mini et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of hENT1 and hENT2 in colon cancer cell lines

et al. 2017

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ABSTRACT. Human equilibrative nucleoside transporters (hENT) 1 and 2, encoded by SLC29A1 and SLC29A2, permit the bidirectional passage of nucleoside analogues into cells and may correlate with clinical responses to chemotherapy in patients with colorectal cancer (CRC). The purpose of this study was to evaluate the expression profiles of SLC29A1 and SLC29A2 in human cancer cell lines. Using quantitative real-time polymerase chain reaction, we comprehensively profiled the transcription levels of SLC29A1 and SLC29A2 in 16 colon cancer cell lines. We validated the ubiquitous and heterogeneous distribution of SLC29A1 and SLC29A2 in human colon cancer cell lines and demonstrated that SLC29A1 was highly expressed in 25% of metastatic cell lines (Colo201 and Colo205) and 62.5% of primary cell lines (Caco2, Colo320, HCT116, RKO, and SW48). For the first time, we showed that both SLC29A1 and SLC29A2 were expressed at lower levels in colon cancer cell lines originating from metastatic sites than from primary sites. These findings indicate that most patients with metastatic CRC (mCRC) may have low hENT1 expression, and treatment with nucleoside analogues may be inefficient. However, some patients still show high hENT1 expression and have a high probability of benefiting from these drugs. Therefore, evaluating transporter expression profiles and different drug responses between primary and metastatic tumors in patients with mCRC is important. Further assessment of the association between hENTs and drug-based treatment of mCRC is required to elucidate the mechanisms of chemotherapy resistance.

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The prognostic significance of human equilibrative nucleoside transporter 1 expression in patients with metastatic bladder cancer treated with gemcitabine‐cisplatin‐based combination chemotherapy

Cited by 34 publications

References 24 publications

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Co-expression of ERCC1 and Snail is a prognostic but not predictive factor of cisplatin-based neoadjuvant chemotherapy for bladder cancer

Differential expression of hENT1 and hENT2 in colon cancer cell lines

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