Potential of metastin and metastin receptor as biomarkers for urological cancers

AIM: To investigate the current state of the research of metastin and metastin receptor in the urological cancer field.METHODS: For analyzing the value of metastin and metastin receptor as molecular biomarkers for the patients with urological cancer, MEDLINE database searches were performed using these terms: metastin, KISS1, kisspeptin, renal(cell) carcinoma(RCC), kidney cancer or urothelial cancer or bladder cancer or prostate cancer or testicular cancer(tumor). Since the articles were evaluated by the validity of the articlesbased on plausibility, credibility, and evidence levels, the articles were graded according to their level of evidence, using the grading system defined by the Oxford Centre for Evidence-based Medicine. RESULTS: A total of six clinical studies published by individual institutions between 2003 and 2013 were included in this review. The article numbers for each of the evidence levels 2a and 2b were three(50%) and three(50%), respectively. Immunohistochemistry and reverse transcriptase-polymerase chain reaction using tumor tissues were performed to analyze in five articles(83%) and in one article(17%). The value of metastin and/or metastin receptor as molecular biomarkers in clear cell RCC, upper tract urothelial carcinoma, and bladder cancer was evaluated by multivariate analysis. Low expression of metastin receptor in clear cell RCC and low expression of metastin in upper tract urothelial carcinoma were significant risk factors for metastasis, and low metastin expression was an independent prognostic factor in bladder cancer. CONCLUSION: Metastin and metastin receptor have potential as suitable molecular biomarkers for urological cancers. However, future studies of metastin and metastin receptor should undergo external validation to ensure consistency across different patient series, since individual institutional studies lack generalization.