Analysis of Formimidoyltransferase Cyclodeaminase as a Potential Prognostic Biomarker and Therapeutic Target in Colorectal Cancer.

IF 2.6 4区医学 Q2 GENETICS & HEREDITY

Cancer Genomics & Proteomics Pub Date : 2026-07-01 DOI:10.21873/cgp.20596

Kenshiro Tanaka, Shinichi Umeda, Norifumi Hattori, Takayoshi Kishida, Koki Nakanishi, Haruyoshi Tanaka, Dai Shimizu, Hideki Takami, Masamichi Hayashi, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Michitaka Fujiwara, Yasuhiro Kodera

{"title":"Analysis of Formimidoyltransferase Cyclodeaminase as a Potential Prognostic Biomarker and Therapeutic Target in Colorectal Cancer.","authors":"Kenshiro Tanaka, Shinichi Umeda, Norifumi Hattori, Takayoshi Kishida, Koki Nakanishi, Haruyoshi Tanaka, Dai Shimizu, Hideki Takami, Masamichi Hayashi, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Michitaka Fujiwara, Yasuhiro Kodera","doi":"10.21873/cgp.20596","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 4","pages":"686-700"},"PeriodicalIF":2.6000,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321703/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Genomics & Proteomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/cgp.20596","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

甲咪甲酰转移酶环脱氨酶作为结直肠癌潜在预后生物标志物和治疗靶点的分析。

背景/目的：甲咪甲酰转移酶环脱氨酶（FTCD）是一种叶酸代谢酶，参与组氨酸分解代谢和细胞内叶酸稳态。虽然FTCD与几种恶性肿瘤的癌症进展和上皮-间质转化（EMT）有关，但其在结直肠癌（CRC）中的肿瘤学作用尚不清楚。本研究探讨FTCD在结直肠癌中的生物学和临床意义。材料和方法：对301例可切除的II/III期CRC患者行根治性切除的CRC细胞系和临床标本进行FTCD表达评估。功能分析，包括增殖、侵袭、迁移和皮下异种移植试验，使用小干扰rna介导的FTCD敲除进行。分析FTCD表达与临床病理因素、复发模式、无病生存期（DFS）和总生存期（OS）之间的关系。使用Kaplan-Meier绘图仪和癌症基因组图谱（TCGA）队列进行外部验证。结果：FTCD敲低可显著抑制CaR-1和COL-3-JCK细胞的增殖、侵袭和迁移，降低肿瘤生长。FTCD表达与多个emt相关基因呈正相关，尤其是COL1A2、SPARC、FZD7和BMP7。FTCD高表达与深部肿瘤侵袭及左侧肿瘤显著相关。FTCD高表达患者的DFS[风险比(HR)=2.00, p=0.012]和OS （HR=2.96, p=0.009）明显较差。在多变量分析中，高FTCD表达仍然是OS的独立预后因素（HR=2.47, p=0.030），但不是DFS的独立预后因素。高FTCD组腹膜和骨复发更为频繁。外部验证队列显示出类似的预后趋势。结论：FTCD可能是一种有用的预后生物标志物，与侵袭性肿瘤行为和不良生存结果相关，可能是CRC的潜在治疗靶点，需要进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Genomics & Proteomics ONCOLOGY-GENETICS & HEREDITY

CiteScore

5.00

自引率

8.00%

发文量

期刊介绍： Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004. Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal. Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.