| PCDH17与TOB1在胃癌中的诊断价值及其对胃癌细胞自噬和凋亡的影响 |
| 投稿时间：2024-09-13 修订日期：2024-09-28 点此下载全文 |
| 引用本文：殷晓霞,李永,沈燕军,张凡,刘博.PCDH17与TOB1在胃癌中的诊断价值及其对胃癌细胞自噬和凋亡的影响[J].医学研究杂志,2025,54(2):159-165 |
| DOI：
10.11969/j.issn.1673-548X.2025.02.025 |
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| 基金项目:河北省张家口市重点研发计划项目(2021129H) |
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| 中文摘要:目的 探讨原钙黏附蛋白17(protocadherin 17, PCDH17)与 ERBB2转导蛋白1(transducer of ERBB2,1, TOB1)在胃癌诊断中的潜在价值,并分析其对胃癌细胞自噬和凋亡的影响,为胃癌诊断提供新的靶点依据。方法 收集120例胃癌患者的胃癌组织和癌旁正常组织,通过免疫组化法检测PCDH17和TOB1在组织中的表达情况。利用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction, RT-qPCR)法和Western blot法检测分析PCDH17和TOB1在胃癌细胞株AGS中的过表达效果,并通过CCK-8、Western blot法及自噬和凋亡相关蛋白检测,评估两者对胃癌细胞增殖、自噬和凋亡的影响。同时,应用受试者工作特征(receiver operating characteristic curve, ROC)曲线评估PCDH17与TOB1联合诊断胃癌的敏感度和特异性。结果 PCDH17和TOB1在胃癌组织中的表达水平显著低于癌旁正常组织(P<0.001),且其低表达与临床分期和淋巴结转移显著相关(P<0.001)。体外实验表明,PCDH17和TOB1过表达能够显著抑制胃癌细胞的增殖(P<0.001),并通过上调自噬相关蛋白LC3、Beclin-1和促凋亡蛋白BAX,抑制抗凋亡蛋白BCL-2,促进胃癌细胞的自噬和凋亡。联合过表达PCDH17和TOB1的细胞增殖抑制作用和自噬、凋亡水平较单独过表达更显著(P<0.001)。PCDH17与TOB1的联合诊断曲线下面积为0.887,敏感度为88.39%,特异性为87.24%,诊断效果优于单独检测。结论 PCDH17与TOB1的低表达与胃癌的发生、发展密切相关,且两者的联合检测在胃癌诊断中具有较高的敏感度和特异性。此外,PCDH17和TOB1的联合过表达在抑制胃癌细胞增殖和促进自噬、凋亡方面具有显著协同作用。PCDH17与TOB1可作为胃癌的潜在诊断标志物和治疗靶点,为胃癌的诊断和靶向治疗提供了新的思路。 |
| 中文关键词:原钙黏附蛋白17 吞噬细胞运动蛋白1 胃癌 |
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| Diagnostic Value of PCDH17 and TOB1 in Gastric Cancer and Their Effects on Autophagy and Apoptosis of Gastric Cancer Cells. |
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| Abstract:Objective To explore the potential diagnostic value of protocadherin 17 (PCDH17) and transducer of ERBB2, (TOB1) in gastric cancer, as well as their effects on autophagy and apoptosis in gastric cancer cells, providing novel target insights for gastric cancer diagnosis. Methods Tissue samples were collected from 120gastric cancer patients, including cancerous and adjacent normal tissues. The expression levels of PCDH17 and TOB1 were assessed via immunohistochemistry. Overexpression of PCDH17 and TOB1 in the AGS gastric cancer cell line was analyzed using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot. The effects of these overexpressions on cell proliferation, autophagy, and apoptosis were evaluated using CCK-8 assays, Western blot analysis, and detection of autophagy and apoptosis-related proteins. Additionally, receiver operating characteristic (ROC) curve analysis was employed to evaluate the sensitivity and specificity of combined PCDH17 and TOB1 in diagnosing gastric cancer. Results The expression levels of PCDH17 and TOB1 were significantly lower in gastric cancer tissues compared to adjacent normal tissues (P<0.001), and their low expression was significantly correlated with clinical stage and lymph node metastasis (P<0.001). In vitro experiments demonstrated that overexpression of PCDH17 and TOB1 could significantly inhibited the proliferation of gastric cancer cells (P<0.001), and promoted autophagy and apoptosis through upregulation of autophagy markers LC3 and Beclin-1, along with pro-apoptotic protein BAX, while downregulating anti-apoptotic protein BCL-2. The combined overexpression of PCDH17 and TOB1 resulted in a more pronounced inhibitory effect on cell proliferation and enhanced levels of autophagy and apoptosis compared to individual overexpression (P<0.001). The area under the curve for the combined diagnostic efficacy of PCDH17 and TOB1 was 0.887, with a sensitivity of 88.39%, and a specificity of 87.24%, the diagnostic effect was superior to that of individual assays. Conclusion The low expression of PCDH17 and TOB1 is closely associated with the occurrence and progression of gastric cancer. Furthermore, the combined detection of these markers exhibits high sensitivity and specificity for gastric cancer diagnosis. The combined overexpression of PCDH17 and TOB1had a significant synergistic effects on inhibiting proliferation while promoting autophagy and apoptosis of gastric cancer cells. PCDH17 and TOB1 can be used as potential diagnostic biomarkers and therapeutic targets for gastric cancer, providing new avenues for the diagnosis and targeted treatment of gastric cancer. |
| keywords:Protocadherin 17 Transducer of oncogenic tyrosine kinase 1 Gastric cancer |
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