Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
Gen Thorac Cardiovasc Surg. 2021 Mar;69(3):525-533. doi: 10.1007/s11748-021-01586-5. Epub 2021 Jan 15.
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.
通过放化疗和手术的多学科治疗，食管鳞状细胞癌（ESCC）患者的预后已经得到改善，但仍较差。晚期、恶性潜能和化疗耐药导致预后不良。在这里，我们试图确定预测 ESCC 患者对化疗反应和预后的因素。
我们检查了 51 名接受化疗后行根治性手术的 ESCC 患者和 23 名仅接受化疗的患者。我们使用来自 74 个化疗前肿瘤组织样本和 67 个化疗后肿瘤组织样本的 RNA 进行了定量逆转录聚合酶链反应基因表达分析，重点关注 PIK3CA、AKT-1、mTOR、4E-BP1、p70S6K、PD-L1 和 PD-L2。
化疗前 AKT-1 和 PD-L1 高表达的患者中，无反应者的比例明显高于有反应者（p=0.034，p=0.020）。多变量分析显示，化疗前 PD-L1 高表达与化疗反应不良相关（比值比 2.998；95%可信区间 1.043-8.619；p=0.042），化疗前 p70S6K 高表达是不良预后因素（风险比 2.518；95%可信区间 1.058-5.988；p=0.037）。此外，化疗后肿瘤中 PD-L1 和 PD-L2 高表达的患者的生存明显差于这些基因低表达的患者（p=0.012，p=0.007）。
这些结果表明，原发性 ESCC 组织中的 PD-L1 和 p70S6K 分别与化疗反应不良和预后不良相关。
