METHODS: This pilot study enrolled 68 patients who received neoadjuvant CRT followed by radical surgery or definitive CRT between 2015 and 2017. Serum specimen was obtained from each patient before treatment and at the time of administration of total doses of 40 Gy.
Cytokines expression analyses were performed in pre- and post-treatment serum using human
cytokine antibody arrays which contained 120 known
tumor-related
cytokines.
RESULTS: Seven differentially expressed
cytokines identified by
cytokine antibody arrays in pre- and post-treatment serum from 4 patients with CRT sensitivity and 4 patients with CRT resistance. Of these, up-regulation of
EGF and uPAR in serum at the doses of 40 Gy were associated with adverse clinical outcomes. The predictive value of
EGF and uPAR were further assessed in a second set of 60 ESCCs. A total of 68 patients enrolled in this study. The median follow-up duration of these patients was 15.87 months (range, 6.21-23.85 months). Cox multivariate survival analyses revealed that high uPAR ratio after CRT independently predicted progression-free survival (PFS) (HR =3.999, 95% CI: 1.503-10.639, P=0.006) and patients with elevated levels of
EGF after CRT exhibited significantly worse overall survival (OS) (HR =2.574, 95% CI: 1.046-6.335, P=0.040). Of note, uPAR expression was significantly positive correlation with
EGF expression in pre- and post-treatment serum (P=0.0001, P=0.0038). Patients with both high
EGF and uPAR ratios had an inferior PFS and OS, compared to patients with a high
EGF ratio only or uPAR ratio only or neither (1-year PFS rate 44.2% vs. 61.4%, 1-year OS rate 64.2% vs. 83.4%, P=0.033 and 0.029, respectively).
CONCLUSIONS: The levels of
EGF and uPAR in serum are reliable and predictive
biomarkers for survival in ESCC patients. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power. We present the following article in accordance with the REMARK reporting checklist.