Combining TRX and TXNIP protein expression levels to assess the factors affecting the prognosis of patients with colorectal cancer
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摘要: 目的:探讨硫氧还蛋白(Trx)与硫氧还蛋白相互作用蛋白(TXNIP)蛋白表达水平对结直肠癌(CRC)患者预后的影响,并结合其他因素对患者预后进行评估。方法:选择于2018年6月—2020年2月进行手术治疗的158例CRC患者作为研究对象。收集患者的常规检查资料并在术后对切除的肿瘤样本组织的Trx和TXNIP表达水平进行检测,术后进行为期1年的随访。比较2种蛋白表达水平不同的患者的临床资料并分析其1年内的生存情况。比较影响患者预后的临床特征,将有差异的因素纳入Cox多因素回归分析,并将独立危险因素构建CRC患者预后风险预测模型,使用验证集数据对预测模型效能进行评价。结果:纳入研究的158例CRC患者88例预后良好,70例预后不良。Trx高表达组与低表达组、TXNIP高表达组与低表达组在临床特征比较上差异均无统计学意义,Trx高表达组患者生存率明显低于低表达组,TXNIP高表达组患者生存率明显高于低表达组。预后良好组与预后不良组患者在TNM分期、T分期、是否存在淋巴结转移、肿瘤分化程度、Trx和TXNIP表达水平的比较上差异有统计学意义(P<0.05)。多因素回归分析结果显示患者处于T3~T4分期、出现淋巴结转移、肿瘤高度分化、Trx表达水平升高及TXNIP表达水平降低是CRC患者预后不良的危险因素(P<0.05)。将上述因素构建用于评估患者预后的Nomogram模型经过一致性系数和校准曲线检验,表明预测值与实际观测值较为一致。结论:Trx表达水平上调和TXNIP表达水平下调与CRC患者预后不良有关,影响患者术后生存率,T分期、淋巴结转移和肿瘤分化程度也与患者预后有密切关系。
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关键词:
- 结直肠癌 /
- 硫氧还蛋白 /
- 硫氧还蛋白相互作用蛋白 /
- 预后
Abstract: Objective: To explore the effect of thioredoxin(Trx) and(thioredoxin interacting protein, TXNIP)expression levels on the prognosis of patients with colorectal cancer, and to evaluate the prognosis of patients in combination with other factors.Methods: One hundred and fifty-eight patients with colorectal cancer who underwent surgical treatment in our hospital from June 2018 to February 2020 were selected as the research objects. The routine examination data of the patients were collected and the Trx and TXNIP protein expression levels of the resected tumor samples were detected after the operation, and a 1-year follow-up was carried out after the operation. Compare the clinical data of two patients with different protein expression levels and analyze their survival within 1 years. Compare the clinical characteristics that affect the prognosis of patients, incorporate the different factors into the Cox multivariate regression analysis, and construct the prognostic risk prediction model for colorectal cancer patients with independent risk factors, and use the validation set data to evaluate the effectiveness of the prediction model.Results: Among the 158 patients with colorectal cancer included in the study, 88 had a good prognosis and 70 had a poor prognosis. There was no significant difference in clinical characteristics between patients with high Trx expression group and low expression group, TXNIP high expression group and low expression group(P>0.05). The survival rate of patients with high Trx expression was significantly lower than that of the low expression group. The survival rate of patients with TXNIP high expression group was significantly higher than that of the low expression group. There are significant differences in the comparison of TNM staging, T staging, lymph node metastasis, tumor differentiation, Trx and TXNIP expression levels between the good prognosis group and the poor prognosis group(P<0.05). Lymph node metastasis, highly differentiated tumors, elevated Trx expression levels, and decreased TXNIP expression levels are risk factors for poor prognosis in patients with colorectal cancer(P<0.05). The Nomogram model constructed by the above factors to evaluate the prognosis of patients was tested by the consistency coefficient and the calibration curve, which showed that the predicted value was more consistent with the actual observation value.Conclusion: The up-regulation of Trx expression level and the down-regulation of TXNIP expression level are related to the poor prognosis of patients with colorectal cancer and affect the survival rate of patients after surgery. T stage, lymph node metastasis and tumor differentiation are also closely related to the prognosis of patients.-
Key words:
- colorectal carcinoma /
- thioredoxin /
- thioredoxin interacting protein /
- prognosis
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[1] Dekker E,Tanis PJ,Vleugels JLA,et al.Colorectal cancer[J].Lancet,2019,394(10207):1467-1480.
[2] Thanikachalam K,Khan G.Colorectal Cancer and Nutrition[J].Nutrients,2019,11(1):164.
[3] Katona BW,Weiss JM.Chemoprevention of Colorectal Cancer[J].Gastroenterology,2020,158(2):368-388.
[4] Wen C,Wang H,Wu X,et al.ROS-mediated inactivation of the PI3K/AKT pathway is involved in the antigastric cancer effects of thioredoxin reductase-1 inhibitor chaetocin[J].Cell Death Dis,2019,10(11):809.
[5] Dunnill CJ,Ibraheem K,Mohamed A,et al.A redox state-dictated signalling pathway deciphers the malignant cell specificity of CD40-mediated apoptosis[J].Oncogene,2017,36(18):2515-2528.
[6] Branco V,Pimentel J,Brito MA,et al.Thioredoxin,Glutathione and Related Molecules in Tumors of the Nervous System[J].Curr Med Chem,2020,27(12):1878-1900.
[7] Qi M,Li L,Lu Y,et al.Proteome profiling to identify peroxiredoxin 1 interacting protein partners in nicotine-associated oral leukoplakia[J].Arch Oral Biol,2019,108(12):104537.
[8] 肖聪,张懿敏,孙圣荣.硫氧还蛋白互作蛋白在乳腺癌中的研究进展[J].医学研究杂志,2019,48(11):5-7,168.
[9] Mauri G,Sartore-Bianchi A,Russo AG,et al.Early-onset colorectal cancer in young individuals[J].Mol Oncol,2019,13(2):109-131.
[10] 李田园.原发肿瘤部位及MSI状态与结直肠癌患者临床病理特征、生存预后的相关性分析[D].郑州:郑州大学,2018.
[11] Wong SH,Yu J.Gut microbiota in colorectal cancer:mechanisms of action and clinical applications[J].Nat Rev Gastroenterol Hepatol,2019,16(11):690-704.
[12] Zhang Y,Park J,Han SJ,et al.Redox regulation of tumor suppressor PTEN in cell signaling[J].Redox Biol,2020,34(5):101553.
[13] Xu LL,Gao W,Chen ZM,et al.Relationships between diabetic nephropathy and insulin resistance,inflammation,Trx,Txnip,CysC and serum complement levels[J].Eur Rev Med Pharmacol Sci,2020,24(22):11700-11706.
[14] Jia JJ,Geng WS,Wang ZQ,et al.The role of thioredoxin system in cancer:strategy for cancer therapy[J].Cancer Chemother Pharmacol,2019,84(3):453-470.
[15] Mohammadi F,Soltani A,Ghahremanloo A,et al.The thioredoxin system and cancer therapy:a review[J].Cancer Chemother Pharmacol,2019,84(5):925-935.
[16] Gong D,Li Y,Wang Y,et al.AMPK α1 Downregulates ROS Levels Through Regulating Trx Leading to Dysfunction of Apoptosis in Non-Small Cell Lung Cancer[J].Onco Targets Ther,2020,13(1):5967-5977.
[17] Wang W,Fang D,Zhang H,et al.Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1[J].Onco Targets Ther,2020,13(47):4691-4704.
[18] Jaganjac M,Milkovic L,Sunjic SB,et al.The NRF2,Thioredoxin,and Glutathione System in Tumorigenesis and Anticancer Therapies[J].Antioxidants(Basel),2020,9(11):1151.
[19] Lin F,Zhang P,Zuo Z,et al.Thioredoxin-1 promotes colorectal cancer invasion and metastasis through crosstalk with S100P[J].Cancer Lett,2017,401(36):1-10.
[20] Alhawiti NM,Al Mahri S,Aziz MA,et al.TXNIP in Metabolic Regulation:Physiological Role and Therapeutic Outlook[J].Curr Drug Targets,2017,18(9):1095-1103.
[21] 莫与琳,杨亚军,崔燎.TXNIP介导的氧化应激在疾病中的作用机制[J].中国药理学通报,2018,34(1):16-19.
[22] 张莉,朱蕾,白洁.miR-135a-5p和TXNIP在甲状腺乳头状癌组织中的表达及意义[J].中国医师杂志,2019,21(8):1195-1198,1204.
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