Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Pathology, Tohoku University Hospital, Sendai, Japan.
Esophagus. 2022 Jul;19(3):436-443. doi: 10.1007/s10388-021-00904-3. Epub 2022 Jan 8.
Thioredoxin reductase 1 (TXNRD1) and heme oxygenase-1 (HO-1) are both involved in the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and play key roles in antioxidant responses. In patients with esophageal squamous cell carcinoma (ESCC), the correlation between the expression of these two proteins and the therapeutic response to neoadjuvant chemoradiation therapy (NACRT), as well as the difference in their expression after chemoradiotherapy, remains unknown.
Proteins involved in the Nrf2 pathway were immunolocalized in carcinoma cells in ESCC patients on NACRT with 5-fluorouracil and cisplatin, followed by esophagectomy. The 8-hydroxydeoxyguanosine (8-OHdG) levels were used to quantify reactive oxygen species. The changes in immunoreactivity before and after NACRT (Δ) were assessed.
Tumor reduction following NACRT was significantly attenuated in pre-therapeutic biopsy specimens associated with high HO-1 status. TXNRD1Δ, HO-1Δ, and 8-OHdGΔ were significantly different in the ineffective and effective groups. The overall survival was significantly lower in high Nrf2 and TXNRD1 groups. In addition, high TXNRD1 expression was an independent prognostic factor in the multivariate analysis of overall survival.
The study findings indicate that HO-1 status in pre-therapeutic biopsy specimens could predict response to NACRT, and TXNRD1 status could predict overall survival of ESCC patients.
硫氧还蛋白还原酶 1（TXNRD1）和血红素加氧酶-1（HO-1）均参与核因子红细胞 2 相关因子 2（Nrf2）途径，在抗氧化反应中发挥关键作用。在食管鳞状细胞癌（ESCC）患者中，这两种蛋白的表达与新辅助放化疗（NACRT）的治疗反应之间的相关性，以及放化疗后它们表达的差异尚不清楚。
在接受氟尿嘧啶和顺铂 NACRT 联合手术治疗的 ESCC 患者的癌组织中，对 Nrf2 途径相关蛋白进行免疫定位。使用 8-羟基脱氧鸟苷（8-OHdG）水平来定量活性氧。评估 NACRT 前后免疫反应性的变化（Δ）。
与高 HO-1 状态相关的 NACRT 前活检标本的肿瘤缩小明显减弱。无效和有效组之间的 TXNRD1Δ、HO-1Δ 和 8-OHdGΔ 差异显著。高 Nrf2 和 TXNRD1 组的总生存率显著降低。此外，高 TXNRD1 表达是总生存率多变量分析的独立预后因素。
研究结果表明，NACRT 前活检标本中 HO-1 状态可预测反应，而 TXNRD1 状态可预测 ESCC 患者的总生存率。
