自噬相关蛋白LC3和beclin-1在膀胱癌中的免疫组化及基因表达情况

LC3 and beclin-1 immunohistochemical and gene expressions in bladder cancer.

作者信息

Hussein Samia, Waley Ahmad Barakat, Abdelgeleel Heba Mahmoud, Saadawy Sara Fouad, Ibrahim Sara Mohammed, Hemeda Mohammed, Sameh Reham

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig, Sharkia, Egypt.

Department of Medical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Sharkia, Egypt.

出版信息

Clin Transl Oncol. 2025 Aug 5. doi: 10.1007/s12094-025-04002-z.

DOI:10.1007/s12094-025-04002-z

PMID:40762938

Abstract

BACKGROUND

In Egypt, bladder cancer is the second most common cancer among men and the fourth most common cancer in the population. It is tightly associated with genetic alterations. Microtubule-associated protein 1 light chain 3B (LC3) is a unique marker of autophagosomes. Beclin-1 participates in the formation of the autophagosome by mediating the localization of other autophagy proteins to the membrane of the pre-autophagosome. Impaired autophagy is linked to the development of several diseases as cancer and autoimmunity. This work aims to investigate the significance of LC3 and beclin-1 immunohistochemical and gene expressions in bladder cancer diagnosis.

METHODS

This study included seventy-four tissue samples of primary urothelial bladder cancer. The tissues were investigated for gene expression, as well as histopathological and immunohistochemical analysis. The genetic and immunohistochemical expressions were correlated with the clinicopathological data.

RESULTS

In the cancerous tissues, there were significant upregulations of LC3 and beclin-1 mRNA and protein expression compared to the adjacent control tissues (P < 0.001 for each). A non-significant positive correlation between LC3 and beclin-1 expression was detected (r =0.212 , P=0.21). Receiver operating curve (ROC) results showed that LC3 at a cut-off point of ≥ 4.3 could be a potential diagnostic marker of bladder cancer with a sensitivity of 96.2% and a specificity of 90.6% (P < 0.001). In addition, beclin-1 at a cut-off point ≥ 2.3 could be a predictor of bladder cancer with a sensitivity of 98% and a specificity of 89% (P < 0.001).

CONCLUSION

LC3 and beclin-1 expressions can be possible diagnostic markers of bladder cancer. Additionally, they are associated with tumor grade and stage.

摘要

背景

在埃及，膀胱癌是男性中第二常见的癌症，也是总体人群中第四常见的癌症。它与基因改变密切相关。微管相关蛋白1轻链3B（LC3）是自噬体的独特标志物。Beclin-1通过介导其他自噬蛋白定位于自噬前体膜来参与自噬体的形成。自噬受损与包括癌症和自身免疫在内的多种疾病的发生发展有关。本研究旨在探讨LC3和Beclin-1免疫组化及基因表达在膀胱癌诊断中的意义。

方法

本研究纳入了74例原发性膀胱尿路上皮癌组织样本。对这些组织进行基因表达检测以及组织病理学和免疫组化分析。将基因和免疫组化表达与临床病理数据进行相关性分析。

结果

与相邻对照组织相比，癌组织中LC3和Beclin-1的mRNA及蛋白表达均显著上调（各P均<0.001）。检测到LC3与Beclin-1表达之间存在无统计学意义的正相关（r = 0.212，P = 0.21）。受试者工作特征曲线（ROC）结果显示，LC3截断值≥4.3时可能是膀胱癌的潜在诊断标志物，敏感性为96.2%，特异性为90.6%（P < 0.001）。此外，Beclin-1截断值≥2.3时可能是膀胱癌的预测指标，敏感性为98%，特异性为89%（P < 0.001）。