Molecular markers to assess short-term disease local recurrence in nasopharyngeal carcinoma

An important challenge in nasopharyngeal carcinoma (NPC) research is to develop effective predictors of tumor recurrence following treatment to determine whether immediate adjuvant therapy is necessary. We retrospectively analyzed archived specimens collected from 45 patients with paired samples of primary NPC (pNPC) and recurrent NPC (rNPC). Clinical samples were collected from the Cancer Center Databases of the First People’s Hospital of Foshan and Shantou Central Hospital (affiliates of Sun Yat-Sen University) between 2001 and 2012. Expression levels of phosphor-Stat3 (p-Stat3), signalosome complex subunit 5 (Jab1/Csn5), Akt1, C/EBP homologous protein (CHOP), Ki-67, and apoptosis were determined by immunohistochemistry in pNPC and rNPC samples from the same patients. Differences in these markers between the short-term interval to recurrence (ITR) group (ITR <18 months) and long-term ITR group (ITR ≥18 months) were further analyzed. In Cox’s regression analysis, the ITR was significantly associated as an independent-negative prognostic factor for overall survival (hazard ratio, 0.211; 95% confidence interval, 0.053–0.841; P=0.027). p-Stat3 was increased in the short-term ITR group (ITR <18 months) and tended to be lower in the long-term ITR group (ITR ≥18 months). In the short-term ITR group, nuclear Akt expression was significantly increased in paired rNPC (P=0.028). In the long-term ITR group, the expression of nuclear Jab1/Csn5 (P=0.047) and assessment of apoptosis measured with TdT-mediated dUTP nick end-labeling (TUNEL) (P=0.003) was significantly increased in paired rNPC. The results suggest that differences between short- and long-term ITR may predict outcome in rNPC. Furthermore, the overexpression of Jab1/Csn5 and Akt may contribute to the carcinogenesis of rNPC, and Akt seems to promote the progression of short-term ITR. Intra-individual changes of Jab1/Csn5, Akt, and TUNEL may help to identify short-term ITR.