Increased keratin 80 expression predicts poor prognosis and promotes oxaliplatin resistance in gastric cancer.

IF 4.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Bo Yang, Hong-Xia Cao, Ya-Wei He, Ji-Jie Ouyang, Meng Lv, Yong-Xiang Li, Yi-Da Lu
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Abstract

Background: Keratin 80 (KRT80), a type I intermediate filament protein, is a member of the keratin family with specialized functions in epithelial tissues. While KRT80 has been implicated in both normal physiological processes and various diseases, its role in gastric cancer (GC), particularly its expression and prognostic significance, remains poorly understood. In this study, we investigated the role and underlying molecular mechanisms of KRT80 in oxaliplatin resistance in GC. Our analysis revealed that KRT80 is significantly upregulated in GC tissues and is associated with poor clinical prognosis. The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.

Aim: To explore the expression of KRT80 in GC and its impact on the prognosis of patients.

Methods: KRT80 expression in GC tissues was analyzed using Western blotting, quantitative reverse transcription PCR, multiple immunofluorescence staining, and immunohistochemistry. Survival analysis was conducted using the Kaplan-Meier method with the log-rank test. The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays. Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1 (EEF1A1) as a binding protein of KRT80.

Results: Integrating our experimental findings with multiple published studies, we found that increased KRT80 expression is associated with poor prognosis in GC and promotes resistance to oxaliplatin. Moreover, we have preliminarily verified the interaction between KRT80 and EEF1A1. Therefore, this study provides a novel perspective on overcoming oxaliplatin resistance in GC.

Conclusion: Increased KRT80 expression predicts poor prognosis and promotes oxaliplatin resistance in GC, suggesting its potential as a novel prognostic biomarker.

背景:角蛋白 80(KRT80)是一种 I 型中间丝蛋白,是角蛋白家族的一员,在上皮组织中具有特殊功能。虽然 KRT80 与正常生理过程和各种疾病都有关系,但其在胃癌(GC)中的作用,尤其是其表达和预后意义,仍鲜为人知。本研究探讨了 KRT80 在胃癌奥沙利铂耐药中的作用及其分子机制。我们的分析发现,KRT80在GC组织中显著上调,并与不良临床预后相关。目的:探讨 KRT80 在 GC 中的表达及其对患者预后的影响:方法:采用Western印迹、定量逆转录PCR、多重免疫荧光染色和免疫组化等方法分析KRT80在GC组织中的表达。采用 Kaplan-Meier 法和对数秩检验进行生存率分析。KRT80 在 GC 细胞增殖中的作用通过体外和体内试验进行了评估。免疫沉淀和质谱分析确定了延伸因子1-α1(EEF1A1)是KRT80的结合蛋白:结果:综合我们的实验结果和已发表的多项研究,我们发现 KRT80 表达的增加与 GC 的不良预后有关,并可促进对奥沙利铂的耐药性。此外,我们还初步验证了 KRT80 与 EEF1A1 之间的相互作用。因此,这项研究为克服 GC 中的奥沙利铂耐药性提供了一个新的视角:结论:KRT80表达的增加可预测GC的不良预后并促进奥沙利铂耐药性的产生,这表明KRT80具有作为新型预后生物标志物的潜力。
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来源期刊
World Journal of Gastroenterology
World Journal of Gastroenterology 医学-胃肠肝病学
CiteScore
7.80
自引率
4.70%
发文量
464
审稿时长
2.4 months
期刊介绍: The primary aims of the WJG are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in gastroenterology and hepatology.
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