自噬相关蛋白在人类胃癌中的预后价值
Prognostic Value of Autophagy-related Proteins in Human Gastric Cancer.
作者信息
Wu Minmin, Chen Bicheng, Pan Xiaodong, Su Jiadong
机构信息
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People's Republic of China.
Department of Transplantation Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Dec 31;12:13527-13540. doi: 10.2147/CMAR.S278354. eCollection 2020.
PURPOSE
Autophagy-related proteins (ATG) play a crucial role in autophagy. Recently, the functions of autophagy in cancer have been gathering attention. However, the prognostic value of ATGs in gastric cancer (GC) has not been explored.
METHODS
The Kaplan-Meier plotter (KM plotter) online database was used to examine the value of ATGs gene expression levels in overall survival (OS) prediction in GC patients with different clinical stage, differentiation, gender, HER2 status, and therapeutic strategy. In vitro experiments applied VE-822, an effective GC treatment, to assess cell migration and proliferation in gastric mucosa epithelial cells, and real-time PCR was used to measure alterations of autophagy-related gene expression.
RESULTS
High , , , and mRNA levels were associated with good OS, while increased , , , , and mRNA levels related to unfavorable OS in patients with GC. overexpression had different effects on OS due to high levels of heterogeneity. High expression was correlated with good OS in female patients with GC and with bad OS for male patients. Additionally, the increased expression was more likely to get a satisfactory OS in patients who underwent surgery alone but was associated with poor OS for patients treated with 5-FU adjuvant. In addition, elevated expression was related to favorable OS for patients with poorly differentiated type, while for patients with moderate differentiation, it was relevant to poor OS. The in vitro experiments showed that berzosertib could significantly inhibit the migration and proliferation of human gastric mucosa epithelial cells, and further real-time PCR assessment of ATG expressions partially coincided with the bioinformation analysis above.
CONCLUSION
These results indicate that individual ATGs have unique prognostic significance interpreted using Kaplan-Meier plotter analysis and in vitro experiments, and this may help guide clinical therapeutic strategy and promote OS by individualizing therapy for GC patients.
目的
自噬相关蛋白（ATG）在自噬过程中发挥关键作用。近年来，自噬在癌症中的功能备受关注。然而，ATG在胃癌（GC）中的预后价值尚未得到探索。
方法
利用Kaplan-Meier plotter在线数据库，研究不同临床分期、分化程度、性别、HER2状态及治疗策略的GC患者中，ATG基因表达水平在总生存期（OS）预测中的价值。体外实验采用有效的GC治疗药物VE-822，评估胃黏膜上皮细胞的迁移和增殖情况，并通过实时定量PCR检测自噬相关基因表达的变化。
结果
在GC患者中，较高的[具体基因1]、[具体基因2]、[具体基因3]和[具体基因4]mRNA水平与较好的OS相关，而[具体基因5]、[具体基因6]、[具体基因7]、[具体基因8]和[具体基因9]mRNA水平升高则与不良OS相关。[具体基因10]过表达因高度异质性对OS有不同影响。高[具体基因11]表达与女性GC患者的良好OS相关，而与男性患者的不良OS相关。此外，[具体基因12]表达增加的患者单独接受手术时更有可能获得满意的OS，但与接受5-FU辅助治疗的患者的不良OS相关。另外，[具体基因13]表达升高与低分化型患者的良好OS相关，而对于中分化患者，则与不良OS相关。体外实验表明，贝佐替布可显著抑制人胃黏膜上皮细胞的迁移和增殖，进一步对ATG表达进行实时定量PCR评估与上述生物信息分析部分相符。
结论
这些结果表明，通过Kaplan-Meier plotter分析和体外实验可知，单个ATG具有独特的预后意义，这可能有助于指导临床治疗策略，并通过为GC患者个体化治疗来提高OS。
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