DPYD, TYMS, TYMP, TK1, and TK2 Genetic Expressions as Response Markers in Locally Advanced Rectal Cancer Patients Treated with Fluoropyrimidine-Based Chemoradiotherapy

Abstract EN

This study is to investigate multiple chemotherapeutic agent- and radiation-related genetic biomarkers in locally advanced rectal cancer (LARC) patients following fluoropyrimidine-based concurrent chemoradiotherapy (CCRT) for response prediction.

We initially selected 6 fluoropyrimidine metabolism-related genes (DPYD, ORPT, TYMS, TYMP, TK1, and TK2) and 3 radiotherapy response-related genes (GLUT1, HIF-1α, and HIF-2α) as targets for gene expression identification in 60 LARC cancer specimens.

Subsequently, a high-sensitivity weighted enzymatic chip array was designed and constructed to predict responses following CCRT.

After CCRT, 39 of 60 (65%) LARC patients were classified as responders (pathological tumor regression grade 2~4).

Using a panel of multiple genetic biomarkers (chip), including DPYD, TYMS, TYMP, TK1, and TK2, at a cutoff value for 3 positive genes, a sensitivity of 89.7% and a specificity of 81% were obtained (AUC: 0.915; 95% CI: 0.840–0.991).

Negative chip results were significantly correlated to poor CCRT responses (TRG 0-1) (P=0.014, hazard ratio: 22.704, 95% CI: 3.055–235.448 in multivariate analysis).

Disease-free survival analysis showed significantly better survival rate in patients with positive chip results (P=0.0001).

We suggest that a chip including DPYD, TYMS, TYMP, TK1, and TK2 genes is a potential tool to predict response in LARC following fluoropyrimidine-based CCRT.