519P - The gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a useful biomarker for proper use of S-1 and tegafur-uracil /leucovo...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Anticancer Agents
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Sotaro Sadahiro
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors S. Sadahiro1, T. Suzuki1, A. Tanaka1, K. Okada1, G. Saito1, A. Kamijo1, H. Nagase2
  • 1Surgery, Tokai University School of Medicine Isehara Campus, 259-1193 - Isehara/JP
  • 2Applied Pharmacology Labo, Taiho Pharmaceutical Co., Ltd., 771-0132 - Tokushima/JP



Preoperative chemoradiotherapy (CRT) with 5-FU-based chemotherapy is the standard of care for locally advanced rectal cancer. Both S-1 and tegafur-uracil (UFT) are 5-FU-based oral drugs. UFT is used in combination with leucovorin (LV) to enhance the effect of 5-FU. S-1 is used without LV and causes the stronger antitumor effect than UFT. We examined the association of the response to CRT with the expression levels of CRT-related genes in tumor tissues before CRT.


Data of 51 patients (pts) with locally advanced rectal cancer who received preoperative CRT at a total radiation dose of 45Gy with S-1 or UFT/LV for 5 weeks were analyzed. The pathological tumor response was assessed according to the tumor regression grade (TRG) criteria. A patient with TRG 1-2 was defined as a responder. The expression levels of CRT-related 18 genes in tumor tissues were determined using a RT-PCR assay. The relationships between tumor response and the gene expression levels were analyzed. The cutoff value for gene expression of gamma-glutamyl hydrolase (GGH) was determined by the ROC curve.


Pathological response (TRG 1-2) and pathological complete response (pCR) was observed in 23 pts (45.1%) and 8 pts (15.7%), respectively. The expression levels of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and glycine amide phosphoribosyl synthetase (GART) were significantly higher in the pCR pts than in the non-pCR pts (p = 0.0091 and p = 0.0477). In UFT/LV group, the gene expression levels of methylenetetrahydrofolate reductase (MTHFR) and GGH were significantly lower in the responders than in non-responders (p = 0.0368 and p = 0.0379). The total pathological response rate of both high-GGH pts in S-1 group and low-GGH pts in UFT/LV group was 65.2%, and was higher than that (45.1%) in all pts.


The expression levels of genes related to folate metabolism in tumor tissue were associated with response to preoperative CRT including S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for determining which regimen, S-1 or UFT/LV, should be used in CRT.

Clinical trial identification

Legal entity responsible for the study



Tokai University


H. Nagase: Is an employee of Taiho Pharmaceutical Co. Ltd. All other authors have declared no conflicts of interest.