Glucose transporter 1 (GLUT1) of anaerobic glycolysis as predictive and prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer

Purpose: We investigated the relationships between biomarkers related to anaerobic glycolytic metabolism (GLUT1, LDH5, PDK1, and HIF-1α proteins), pathologic response, and prognosis. Methods: All stage II and stage III rectal cancer patients had 50.4 Gy (1.8 Gy/day in 28 fractions) over 5.5 weeks, plus 5-fluorouracil (425 mg/m²/day) and leucovorin (20 mg/m ²/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GLUT1, LDH5, PDK1, and HIF-1α proteins was determined by immunohistochemistry and was assessed in 104 patients with rectal cancer treated with neoadjuvant chemoradiotherapy. Results: This study included stage II and III rectal cancer patients, and each stage accounted for each 50 % of the total cases. A high expression of GLUT1 protein was associated with a significantly lower rate of ypCR compared with low expression of GLUT1 protein (4.0 % vs. 27.8 %, respectively; p = 0.012). GLUT1 expression was also significantly higher in the poor response group (Grade 0, 1) than in the good response group (Grade 2, 3) (34.0 % vs. 14.8 %, respectively; p = 0.022). In recurrence analysis, the expression of GLUT1 protein demonstrated a significant correlation with time to recurrence, based on a log-rank method (p = 0.016). When analyzed by multiple Cox regression, the positive expression of GLUT1 was the most significant and independent unfavorable prognostic factor (p = 0.004). Conclusions: GLUT1 expression is a predictive and prognostic factor for pathologic complete response and recurrence in rectal cancer patients treated with 5-flurouracil and leucovorin neo-adjuvant chemoradiotherapy.