Prognostic impact of blood biomarkers TS and DPD in neoadjuvant-treated esophageal cancer patients.
OBJECTIVE
The prognostic value of TS (thymidylate synthase) and DPD (dihydropyrimidine dehydrogenase) RNA expression in the blood of patients with esophageal cancer is not known. The aim of the present study was to evaluate the significance of these molecular alterations in the blood as a prognostic marker for patients with neoadjuvant-treated esophageal cancer.


METHODS
A total of 29 patients with locally advanced esophageal cancer (cT3-T4, Nx, M0) were enrolled in this prospective study. All patients received neoadjuvant chemoradiation followed by a transthoracic resection (curative transthoracic en bloc esophagectomy, RO). Peripheral blood samples were drawn before initiation of therapy. The analysis was performed using quantitative real-time-polymerase chain reaction (RT-PCR). The histomorphological regressions grading after neoadjuvant therapy was defined as follows: major response (MaR)=less than 10% vital tumor tissue, minor response (MiR)=more than 10% vital tumor tissue.


RESULTS
Nineteen out of 29 patients (65.5%) had a MiR and 10 (34.5%) had a MaR. The median survival of patients was 2.08 years (range=0.15-4.53). Among the tested genes, the RNA expression of TS was significantly associated with prognosis of patients. Patients with TS expression above 0.78 had a median survival of 1.1 years (range=0.21-3.96) compared to 2.6 years (range=0.15 to 4.53) in patients with TS expression lower than 0.78 (p=0.031, log rank test). There was no association between clinical variables (e.g., tumor stage, gender, age, etc.) and the RNA expression of TS in the serum.


CONCLUSIONS
The RNA expression of TS in the blood is a potential prognostic marker in patients with neoadjuvant-treated esophageal cancer. The significance of these molecular alterations as non-invasive prognostic marker for esophageal cancer should be evaluated in prospective studies.
Department of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany peter.grimminger@uk-koeln.de.
Peter P
PP
Grimminger
Department of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany.
Martin K H
MK
Maus
Department of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany.
Juliane
J
Bergenthal
Department of General and Visceral Surgery, St. Antonius Hospital, Cologne, Germany.
Christoph
C
Wandhöfer
Department of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany.
Ullrich K
UK
Fetzner
Department of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany.
Till
T
Herbold
Department of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany.
Elfriede
E
Bollschweiler
Department of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany.
Arnulf H
AH
Hölscher
Department of General and Visceral Surgery, St. Antonius Hospital, Cologne, Germany.
Jan
J
Brabender
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000097:blood / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D013940:Thymidylate Synthase / Q000097:blood / Q000235:genetics*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase
DPD; Peripheral blood; TS; biomarker; esophageal cancer; neoadjuvant; prospective; survival