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Published on: September 30, 2016
Analysis of Formimidoyltransferase Cyclodeaminase as a Potential Prognostic Biomarker and Therapeutic Target in
Kenshiro Tanaka1, Shinichi Umeda2, Norifumi Hattori1
1Department of Surgery (Gastrointestinal Surgery), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Background/Aim:
Formimidoyltransferase cyclodeaminase (FTCD) is a folate-metabolizing enzyme involved in histidine catabolism and intracellular folate homeostasis. Although FTCD has been implicated in cancer progression and epithelial-mesenchymal transition (EMT) in several malignancies, its oncological role in colorectal cancer (CRC) remains unclear. This study investigated the biological and clinical significance of FTCD in CRC.
Materials And Methods:
FTCD expression was evaluated in CRC cell lines and clinical specimens from 301 patients with resectable stage II/III CRC who underwent curative resection. Functional analyses, including proliferation, invasion, migration, and subcutaneous xenograft assays, were performed using small interfering RNA-mediated FTCD knockdown. Associations between FTCD expression and clinicopathological factors, recurrence patterns, disease-free survival (DFS), and overall survival (OS) were analyzed. External validation was performed using Kaplan-Meier Plotter and The Cancer Genome Atlas (TCGA) cohorts.
Results:
FTCD knockdown significantly suppressed proliferation, invasion, and migration in CaR-1 and COL-3-JCK cells and reduced tumor growth in vivo. FTCD expression positively correlated with multiple EMT-related genes, particularly COL1A2, SPARC, FZD7, and BMP7. High FTCD expression was significantly associated with deeper tumor invasion and left-sided tumors. Patients with high FTCD expression showed significantly worse DFS [hazard ratio (HR)=2.00, p=0.012] and OS (HR=2.96, p=0.009). In multivariate analysis, high FTCD expression remained an independent prognostic factor for OS (HR=2.47, p=0.030), but not for DFS. Peritoneal and bone recurrences were more frequent in the high FTCD group. External validation cohorts showed similar prognostic trends.
Conclusion:
FTCD may serve as a useful prognostic biomarker associated with aggressive tumor behavior and poor survival outcomes and may be a potential therapeutic target requiring further validation in CRC.
