High orotate phosphoribosyltransferase gene expression predicts complete response to chemoradiotherapy in patients with squamous cell carcinoma of the esophagus.
OBJECTIVE
Chemoradiotherapy (CRT) is a possible alternative to surgery for esophageal cancer. As complete response (CR) to CRT is essential for a good prognosis, potential biomarkers predictive of CR were explored.


METHODS
Endoscopic tumor biopsies were obtained from 41 patients with stage II-III esophageal squamous cell carcinoma before 5-fluorouracil/cisplatin-based definitive CRT. cDNA was derived from RNA isolated from microdissected tumor cells. mRNA expression levels of 10 genes involved in CRT or tumor biology were measured using quantitative real-time RT-PCR.


RESULTS
Expression levels of orotate phosphoribosyltransferase (OPRT) and dihydrofolate reductase mRNA were significantly higher in the CR group compared with the non-CR group (p = 0.0206 and 0.0191, respectively). Matrix metalloproteinase 9 mRNA expression was significantly lower in the CR group (p = 0.0436). CR rates were significantly higher in patients with node-negative disease and high expression levels of OPRT and dihydrofolate reductase genes (p = 0.0448, 0.0104 and 0.0104, respectively). No significant difference in CR rates was observed for other variables. Multivariate analysis revealed that high OPRT gene expression was an independent predictive factor of CR (p = 0.0192). It was also significantly associated with good prognosis (p = 0.0450).


CONCLUSIONS
High OPRT gene expression may be a predictive factor of CR to 5-fluorouracil/cisplatin-based CRT in esophageal cancer.
Kajiwara
Takeshi
T
Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
Nishina
Tomohiro
T
Hyodo
Ichinosuke
I
Moriwaki
Toshikazu
T
Endo
Shinji
S
Nasu
Junichirou
J
Hori
Shinichiro
S
Matsuura
Bunzo
B
Hiasa
Yoichi
Y
Onji
Morikazu
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011879:Radiotherapy Dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome
D012333:RNA, Messenger; D009962:Orotate Phosphoribosyltransferase; D002945:Cisplatin; D005472:Fluorouracil