Biomarkers predicting the response to chemotherapy and the prognosis in patients with esophageal squamous cell carcinoma.

Abstract

The prognosis of patients with esophageal squamous cell carcinoma (ESCC) has been improved by multidisciplinary therapy with chemoradiotherapy and surgery, but it remains poor. Advanced stage, malignant potential, and chemo-resistance contribute to the poor prognosis. Here, we attempted to identify predictive factors of the response to chemotherapy and the prognosis of ESCC patients. We examined 51 ESCC patients who were treated with chemotherapy followed by radical surgery, and 23 patients who were treated with chemotherapy alone. We conducted quantitative reverse transcription-polymerase chain reaction gene expression analysis using RNA extracted from 74 tumor tissue samples collected before chemotherapy and 67 tumor tissue samples collected after chemotherapy, focusing on PIK3CA, AKT-1, mTOR, 4E-BP1, p70S6K, PD-L1, and PD-L2. The proportions of patients with high expressions of AKT-1 and PD-L1 before chemotherapy were significantly higher among the non-responders than among the responders (p = 0.034, p = 0.020, respectively). Multivariate analyses revealed that high PD-L1 expression before chemotherapy was associated with poor response to chemotherapy (odds ratio 2.998; 95% CI 1.043-8.619; p = 0.042) and high p70S6K expression before chemotherapy was a poor prognostic factor (hazard ratio 2.518; 95% CI 1.058-5.988; p = 0.037). In addition, the patients with high expression of PD-L1 and PD-L2 in the tumors after chemotherapy had significantly worse survival than those with low expression of these genes (p = 0.012, p = 0.007, respectively). These results demonstrated that PD-L1 and p70S6K in the primary ESCC tissues were related to a poor response to chemotherapy and poor prognosis, respectively.