Noriko Iwata1, Toshiaki Ishikawa2, Satoshi Okazaki1, Kaoru Mogushi3, Hironobu Baba1, Megumi Ishiguro4, Hirotoshi Kobayashi1, Hiroshi Tanaka3, Tatsuyuki Kawano1, Kenichi Sugihara5, Hiroyuki Uetake5. 1. Division of Surgical Gastroenterology, Tokyo Medical and Dental University, Tokyo, Japan. 2. Division of Surgical Specialties, Tokyo Medical and Dental University, Tokyo, Japan ishi.srg2@tmd.ac.jp. 3. Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, Tokyo, Japan. 4. Department of Translational Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. 5. Division of Surgical Specialties, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
BACKGROUND: This study investigated abnormal methylation in colorectal cancer (CRC) and the potential role of the Quaking RNA-binding protein (QKI) gene in tumorigenesis. MATERIALS AND METHODS: Oligonucleotide microarray expression profiling was carried out on a panel of primary CRC specimens (n=17) and CRC cell lines (n=5), followed by methylation analysis using methylation-specific polymerase chain reaction. QKI expression levels were assessed in 156 primary CRCs by qRT-PCR and immunohistochemistry. RESULTS: Low QKI expression was observed in 47.7% in CRCs. QKI promoter methylation was detected in 32.1% of patients with CRC, and in these patients mRNA expression in tumor tissue was significantly down-regulated compared to matched normal tissues (p=0.049). There was a significant relationship between low QKI expression and recurrence after surgery (p=0.004). Low QKI expression was an independent risk factor for recurrence after surgery in 153 patients with CRC without distant metastases (p=0.036). CONCLUSION: Patients with tumors expressing low levels of QKI experienced significantly higher rates of tumor recurrence after curative surgery and worse prognoses. Methylation of the QKI promoter and concomitant reduced expression of QKI mRNA may be important for CRC initiation and progression. Loew QKI expression may be a useful clinical biomarker for predicting recurrence and prognosis. Copyright
BACKGROUND: This study investigated abnormal methylation in colorectal cancer (CRC) and the potential role of the Quaking RNA-binding protein (QKI) gene in tumorigenesis. MATERIALS AND METHODS:Oligonucleotide microarray expression profiling was carried out on a panel of primary CRC specimens (n=17) and CRC cell lines (n=5), followed by methylation analysis using methylation-specific polymerase chain reaction. QKI expression levels were assessed in 156 primary CRCs by qRT-PCR and immunohistochemistry. RESULTS: Low QKI expression was observed in 47.7% in CRCs. QKI promoter methylation was detected in 32.1% of patients with CRC, and in these patients mRNA expression in tumor tissue was significantly down-regulated compared to matched normal tissues (p=0.049). There was a significant relationship between low QKI expression and recurrence after surgery (p=0.004). Low QKI expression was an independent risk factor for recurrence after surgery in 153 patients with CRC without distant metastases (p=0.036). CONCLUSION:Patients with tumors expressing low levels of QKI experienced significantly higher rates of tumor recurrence after curative surgery and worse prognoses. Methylation of the QKI promoter and concomitant reduced expression of QKI mRNA may be important for CRC initiation and progression. Loew QKI expression may be a useful clinical biomarker for predicting recurrence and prognosis. Copyright
Authors: Jennyfer M García-Cárdenas; Santiago Guerrero; Andrés López-Cortés; Isaac Armendáriz-Castillo; Patricia Guevara-Ramírez; Andy Pérez-Villa; Verónica Yumiceba; Ana Karina Zambrano; Paola E Leone; César Paz-Y-Miño Journal: Front Mol Biosci Date: 2019-08-07