Predictive and Prognostic Value of Ribonucleotide Reductase Regulatory Subunit M1 and Excision Repair Cross-Complementation Group 1 in Advanced Urothelial Carcinoma (UC) Treated with First-Line Gemcitabine Plus Platinum Combination Chemotherapy

• Published in: PloS one 2015-07, Vol.10 (7), p.e0133371-e0133371
• Main Authors: Kim, Miso, Ku, Ja Hyeon, Kwak, Cheol, Kim, Hyeon Hoe, Lee, Eunsik, Keam, Bhumsuk, Kim, Tae Min, Heo, Dae Seog, Lee, Se-Hoon, Moon, Kyung Chul
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biomarkers; Bladder cancer; Cancer; Cancer therapies; Care and treatment; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Combination drug therapy; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxyribonucleic acid; Disease-Free Survival; DNA; DNA-Binding Proteins - biosynthesis; Endonucleases - biosynthesis; ERCC1 protein; Female; Gemcitabine; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Hematology; Hospitals; Humans; Immunohistochemistry; Internal medicine; Lung cancer; Male; Medical prognosis; Medical research; Medicine; Metastases; Middle Aged; Multivariate analysis; Oncology; Patients; Platinum; Predictive Value of Tests; Prognosis; Reductase; Repair; Response rates; Ribonucleotide reductase; Survival; Survival Rate; Tumor Suppressor Proteins - biosynthesis; Tumors; Urogenital system; Urologic Neoplasms - drug therapy; Urologic Neoplasms - metabolism; Urologic Neoplasms - mortality; Urology; Urothelial carcinoma
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133371

Preclinical and clinical studies have suggested that expression of ribonucleotide reductase regulatory subunit M1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) is associated with resistance to gemcitabine and cisplatin, respectively. We evaluated the significance of RRM1 and ERCC1 expression to predict tumor response to gemcitabine plus platinum chemotherapy (GP) and survival in advanced UC. We retrospectively collected tumor samples and reviewed clinical data of 53 patients with unresectable or metastatic UC, who were treated with first-line GP. RRM1 and ERCC1 expression were measured by immunohistochemistry. Among 53 patients, 12 (22.6%) and 26 (49.1%) patients had tumors that demonstrated a high expression for RRM1 and ERCC1, respectively. Twenty-nine (70.7%) of 41 patients with low RRM1 expression achieved a clinical response (complete + partial responses), but only 3 (25.0%) of 12 patients with high RRM1 expression achieved a clinical response after GP (P=0.007). Nineteen (70.4%) of 27 patients with low ERCC1 expression achieved a clinical response, while 13 (50.0%) of 26 patients with high ERCC1 expression achieved a clinical response (P=0.130). High RRM1 expression was associated with shorter progression free survival and overall survival (PFS P=0.006, OS P=0.006). Multivariate analysis confirmed that patients with high RRM1 expression had a significantly greater risk of progression and death than those with low RRM1 expression. ERCC1 status was not a significant predictor for PFS and OS. RRM1 expression was predictive and prognostic of clinical outcome in advanced UC treated with gemcitabine plus platinum combination chemotherapy.