Integrating Clinical and Molecular Insights: CTPS1 as a Key Biomarker of Tumor Progression and Prognosis in Colorectal Adenocarcinoma

Abstract

Colorectal cancer (CRC) remains a leading cause of global cancer-related mortality. Cytidine triphosphate synthase 1 (CTPS1) is an essential enzyme for DNA synthesis and cell cycle progression. While CTPS1 has been implicated in the pathogenesis of various malignancies, its clinical significance in colorectal adenocarcinoma remains poorly defined. This study aimed to investigate the immunohistochemical (IHC) expression of CTPS1 in colorectal adenocarcinoma and evaluate its association with clinicopathological features and survival outcomes. CTPS1 expression was assessed via IHC in 168 colorectal adenocarcinoma specimens and 142 matched adjacent non-neoplastic tissues. Statistical associations with clinicopathological parameters were analyzed using χ 2 or Fisher exact tests. Progression-free survival (PFS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and compared via the log-rank test. Multivariate Cox proportional hazards regression was employed to identify independent prognostic factors. CTPS1 expression was significantly upregulated in tumour tissues compared with adjacent normal mucosa ( P <0.001). High CTPS1 expression was observed in 55.4% of tumor samples and significantly correlated with advanced T stage, TNM stage, and modified Dukes staging, as well as nodal involvement, distant metastasis, tumor recurrence, and elevated serum CEA levels. Furthermore, elevated CTPS1 was associated with aggressive histologic features, including higher grade, tumor budding, poorly differentiated clusters (PDCs), and tumor deposits. Both PFS and DFS were significantly shorter in patients with high CTPS1 expression ( P <0.001). Multivariate analysis confirmed that high CTPS1 expression, along with nodal status and tumor recurrence, was an independent prognostic factor for both PFS and DFS. Therefore, CTPS1 is a robust independent prognostic indicator and a marker of aggressive progression in colorectal adenocarcinoma. These findings suggest that CTPS1 is a promising biomarker for risk stratification and may guide clinical decision-making in the management of CRC.