Clinical Significance of Methylation and Reduced Expression of the Quaking Gene in Colorectal Cancer.
This study investigated abnormal methylation in colorectal cancer (CRC) and the potential role of the Quaking RNA-binding protein (QKI) gene in tumorigenesis.



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.



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).



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.
Division of Surgical Gastroenterology, Tokyo Medical and Dental University, Tokyo, Japan.
Noriko
N
Iwata
Division of Surgical Specialties, Tokyo Medical and Dental University, Tokyo, Japan ishi.srg2@tmd.ac.jp.
Toshiaki
T
Ishikawa
Division of Surgical Gastroenterology, Tokyo Medical and Dental University, Tokyo, Japan.
Satoshi
S
Okazaki
Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Kaoru
K
Mogushi
Division of Surgical Gastroenterology, Tokyo Medical and Dental University, Tokyo, Japan.
Hironobu
H
Baba
Department of Translational Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Megumi
M
Ishiguro
Division of Surgical Gastroenterology, Tokyo Medical and Dental University, Tokyo, Japan.
Hirotoshi
H
Kobayashi
Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Hiroshi
H
Tanaka
Division of Surgical Gastroenterology, Tokyo Medical and Dental University, Tokyo, Japan.
Tatsuyuki
T
Kawano
Division of Surgical Specialties, Tokyo Medical and Dental University, Tokyo, Japan.
Kenichi
K
Sugihara
Division of Surgical Specialties, Tokyo Medical and Dental University, Tokyo, Japan.
Hiroyuki
H
Uetake
D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D059467:Transcriptome
C490832:QKI protein, human; D016601:RNA-Binding Proteins
Colorectal cancer; QKI; Quaking RNA-binding protein gene; methylation; prognostic factor; tumor-suppressor gene