Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Because of the lack of reliable prognostic and predictive biomarkers for CRC, most patients are often diagnosed at a late stage. The tryptophan–kynurenine pathway plays a crucial role in promoting cancer progression. Kynurenine is considered an oncometabolite in colon cancer, and its downstream metabolites are also associated with CRC. Kynurenine 3-monooxygenase (KMO), a pivotal enzyme that catalyzes kynurenine metabolism, is essential for several cellular processes. In the current study, we explored the role of KMO in CRC. Immunohistochemical results showed that KMO was upregulated in CRC tissues relative to paired healthy tissue and polyps. Moreover, CRC patients with higher KMO expression were associated with higher metastasis and poorer survival rates. Knockdown of KMO decreased the expression of cancer stem cell markers, as well as the sphere-forming, migration, and invasion abilities of CRC cells. Additionally, blockade of the enzymatic activity of KMO using an inhibitor suppressed sphere formation and cell motility in CRC cells. These findings suggest the clinical relevance of KMO in CRC tumorigenesis and aggressiveness.
Highlights
Colorectal cancer (CRC) ranks as the third-highest cause of cancer-related deaths and has increasing incidence in Taiwan [1]
The results showed that Kynurenine 3-monooxygenase (KMO) expression in tumor tissues was significantly higher than that in normal tissues (Figure 1B)
To further validate the clinical relevance of KMO, we examined data from the TCGA database and found that CRC patients with higher KMO transcript levels were associated with worse disease-free survival (DFS) (Figures 2B,C)
Summary
Colorectal cancer (CRC) ranks as the third-highest cause of cancer-related deaths and has increasing incidence in Taiwan [1]. Different molecular subtypes of CRC exhibit distinct genetic signatures and clinical outcomes. Mutations, including RAS, BRAF, PIK3CA, APC, TP53 mutations, and loss of PTEN expression, are usually present in metastatic CRC, and some of these genes have been suggested as promising predictive markers, and some act as predictive markers [2, 3]. Relapse, and drug resistance lead to poor prognosis in CRC, despite advances in CRC treatments, such as radiotherapy, surgery, and chemotherapy [4, 5]. Considering the high morbidity and modest effectiveness of CRC treatment, identifying reliable biomarkers of prognosis and therapeutic targets for patients with CRC is of paramount importance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
