Expression profile of apoptosis-related genes potentially explains early recurrence after definitive chemoradiation in esophageal squamous cell carcinoma

Abstract

Definitive chemoradiation is a curative treatment option for patients with locoregional esophageal squamous cell carcinoma (ESCC) who are not suitable for surgical resection, but many tend to develop local recurrence. The purpose of the study was to investigate factors affecting local recurrence of the tumor. Seventy-two patients with stage II-III thoracic ESCC who received definitive concurrent chemoradiation (CRT) and completely responded to the treatment were enrolled into this study. The case patients were 49 patients who recurred locally within 24 months after definitive CRT and 23 patients who did not have a local recurrence within 24 months were considered as controls. We investigated whether dysregulation of apoptosis-related genes was associated with early tumor recurrence. Quantitative real-time polymerase chain reaction showed upregulation of BCLAF1 and downregulation of BAG4, CARD6, IGF1R, and TNF in the tissues of case patients, as compared with controls. Among the patients with recurrent ESCC, those with tumors which exhibited more than twofold upregulated BCLAF1 and more than twofold downregulated BAG4 and TNF had a decreased time interval to local recurrence. Three gene pairs of the downregulated genes showed a significant correlation with local recurrence: BAG4 and CARD6, BAG4 and TNF, CARD6, and TNF. The patients with T3-4 disease and those with tumor >3 cm in length had a trend toward early local recurrence, though the associations were not reached statistical significance. Upregulation of BCLAF1 and downregulation of BAG4 and TNF was independently associated with early local recurrence in multivariate analysis (P < 0.05). This study supports the involvement of apoptosis-related genes in early tumor recurrence after definitive chemoradiation in patients with stage II-III thoracic ESCC.