Al-Hadyan Khaled S, Storr Sarah J, Zaitoun Abed M, Lobo Dileep N, Martin Stewart G
Nottingham Breast Cancer Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
Diseases. 2024 Sep 24;12(10):227. doi: 10.3390/diseases12100227.
Poor survival outcomes in periampullary cancer highlight the need for improvement in biomarkers and the development of novel therapies. Redox proteins, including the thioredoxin system, play vital roles in cellular antioxidant systems. In this retrospective study, thioredoxin (Trx), thioredoxin-interacting protein (TxNIP), and thioredoxin reductase (TrxR) protein expression was assessed in 85 patients with pancreatic ductal adenocarcinoma (PDAC) and 145 patients with distal bile duct or ampullary carcinoma using conventional immunohistochemistry. In patients with PDAC, high cytoplasmic TrxR expression was significantly associated with lymph node metastasis ( = 0.033). High cytoplasmic and nuclear Trx expression was significantly associated with better overall survival ( = 0.018 and = 0.006, respectively), and nuclear Trx expression remained significant in multivariate Cox regression analysis ( < 0.0001). In distal bile duct and ampullary carcinomas, high nuclear TrxR expression was associated with vascular ( = 0.001) and perineural ( = 0.021) invasion, and low cytoplasmic TxNIP expression was associated with perineural invasion ( = 0.025). High cytoplasmic TxNIP expression was significantly associated with better overall survival ( = 0.0002), which remained significant in multivariate Cox regression analysis ( = 0.013). These findings demonstrate the prognostic importance of Trx system protein expression in periampullary cancers.
壶腹周围癌较差的生存结果凸显了改进生物标志物和开发新疗法的必要性。包括硫氧还蛋白系统在内的氧化还原蛋白在细胞抗氧化系统中发挥着至关重要的作用。在这项回顾性研究中，使用传统免疫组织化学方法评估了85例胰腺导管腺癌（PDAC）患者和145例远端胆管或壶腹癌患者的硫氧还蛋白（Trx）、硫氧还蛋白相互作用蛋白（TxNIP）和硫氧还蛋白还原酶（TrxR）蛋白表达情况。在PDAC患者中，高细胞质TrxR表达与淋巴结转移显著相关（P = 0.033）。高细胞质和细胞核Trx表达分别与更好的总生存期显著相关（P = 0.018和P = 0.006），并且在多变量Cox回归分析中细胞核Trx表达仍然显著（P < 0.0001）。在远端胆管和壶腹癌中，高细胞核TrxR表达与血管侵犯（P = 0.001）和神经周围侵犯（P = 0.021）相关，而低细胞质TxNIP表达与神经周围侵犯相关（P = 0.025）。高细胞质TxNIP表达与更好的总生存期显著相关（P = 0.0002），在多变量Cox回归分析中仍然显著（P = 0.013）。这些发现证明了硫氧还蛋白系统蛋白表达在壶腹周围癌中的预后重要性。
