Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer.
The aim was to determine changes in dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) mRNAs in the blood of advanced gastric cancer (AGC) patients to see whether these enzymes affected the patients' response to S-1-based chemotherapy and prognosis. For this purpose, pretreatment DPD/TS mRNA expressions were determined in 40 AGC patients using RT-PCR. The patients were then administered with S-1-based regimen (S-1 + cisplatin) and toxicities were recorded. The relationship between the DPD/TS mRNA expressions and the chemotherapy response, drug resistance, and prognosis was analyzed. The data show that DPD mRNA expression correlated significantly with Lauren type while TS mRNA expression correlated with distant metastasis. Patients with higher DPD and/or TS mRNA expression(s) showed poor response, while those with low DPD mRNA expression showed better response to the chemotherapy. Pooled analysis showed that the patients with low DPD/TS mRNA expressions had better therapeutic response. The incidence of bone marrow suppression, diarrhea, and oral mucositis was high in patients with low DPD mRNA expression. Median overall survival (OS) in 40 patients was 13.5 months. It was 17 months for low and 10 months for high DPD (P = 0.044) and TS mRNA expression (P = 0.047). Pooled analysis showed that the patients with both low DPD/TS mRNA expressions had longer OS (P = 0.001). In conclusion, the detection of DPD and/or TS mRNA expression can be used to predict the response to S-1-based chemotherapy, drug resistance, and prognosis in AGC patients as well as to help guide the individualized treatment of gastric cancer.
Department of Oncology, Suzhou Xiangcheng People's Hospital, Suzhou, 215131, Jiangsu Province, China.
Xiao-Ming
XM
Shen
Department of Radiation Oncology, Xuzhou Central Hospital, Xuzhou, 221009, Jiangsu Province, China.
Chong
C
Zhou
Department of Oncology, Suzhou Xiangcheng People's Hospital, Suzhou, 215131, Jiangsu Province, China.|Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, China.
Lian
L
Lian
Department of Oncology, Suzhou Xiangcheng People's Hospital, Suzhou, 215131, Jiangsu Province, China.
Li-Qun
LQ
Li
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, China. liwei10@suda.edu.cn.
Wei
W
Li
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, China. mtao@medmail.com.cn.
Min
M
Tao
D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D005641:Tegafur / Q000494:pharmacology* / Q000627:therapeutic use; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
D012333:RNA, Messenger; D005641:Tegafur; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase
Advanced gastric cancer; Dihydropyrimidine dehydrogenase; S-1; Thymidylate synthase