mRNA Expression of COX-2, CXCL1, and IMP3 with Pharmacogenomic Variations in MTHFR, DPYD, and TYMS Genes in Colorectal Cancer: A Hospital-Based Study
摘要
Colorectal cancer (CRC) is an emerging public health challenge in India, with a rising incidence, particularly among younger populations. In addition to conventional clinicopathological staging, molecular biomarkers may provide important insights into tumor biology, prognosis, and therapeutic response. This hospital-based pilot case–control study included 30 histologically confirmed CRC patients treated at Shyam Shah Medical College and Sanjay Gandhi Memorial Hospital, Rewa, during 2023–2024, with paired adjacent normal mucosa serving as controls. mRNA expression of COX-2, CXCL1, and IMP3 was assessed using quantitative real-time PCR, while MTHFR C677T, DPYD rs3918290, and TYMS polymorphisms were analyzed by PCR–RFLP. Associations with clinic-pathological variables and survival outcomes were evaluated using appropriate statistical methods, including Kaplan–Meier analysis. The mean age of patients was 52.7 years, with a male predominance (56.7%); most cases were moderately differentiated adenocarcinomas (86%), and 30% presented at advanced stages. Tumor tissues showed significant over-expression of COX-2 and CXCL1 compared with adjacent normal mucosa (p < 0.05), whereas IMP3 expression did not differ significantly. Higher COX-2 expression was observed among female patients (p = 0.009). The MTHFR C677T TT genotype was detected in 60% of patients and appeared to confer a protective effect, while the CC genotype was associated with increased chemotherapy-related toxicity. DPYD variants were linked to fluoropyrimidine-associated adverse events, whereas TYMS polymorphisms showed no significant association. Patients who received chemotherapy for more than three months demonstrated significantly improved survival (p = 0.012). These findings suggest that COX-2 and CXCL1 may serve as potential diagnostic biomarkers in CRC, and that MTHFR and DPYD polymorphisms influence chemotherapy response. Integration of molecular and pharmacogenetic profiling may support more personalized management of CRC in the Indian population.