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Claudin-12 表达降低预示宫颈癌预后不良。

Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer.

机构信息

Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.

Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.

出版信息

Int J Mol Sci. 2021 Apr 6;22(7):3774. doi: 10.3390/ijms22073774.

Abstract

BACKGROUND

Within the claudin (CLDN) family, mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications.

METHODS

We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer.

RESULTS

Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, = 0.002 and HR 2.615, = 0.029, respectively).

CONCLUSIONS

It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.

摘要

背景

在紧密连接蛋白(CLDN)家族中,多种类型的癌症存在 mRNA 表达改变,但由于缺乏广泛应用的特异性抗体(Abs),其临床病理相关性尚未确定。

方法

我们针对人/鼠 CLDN12 生成了一种单克隆 Ab(mAb),并验证了其特异性。通过进行免疫组织化学染色和半定量分析,我们评估了 138 例宫颈癌组织中 CLDN12 表达与临床病理参数之间的关系。

结果

Western blot 和免疫组织化学分析表明,该建立的 mAb 可特异性识别 CLDN12 蛋白。在 138 例病例中,有 26 例(18.8%)表现为 CLDN12 低表达,与 CLDN12 高表达组相比,疾病特异性生存率(DSS)和无复发生存率明显降低。我们还通过单变量和多变量分析表明,CLDN12 低表达是宫颈癌患者 DSS 的显著预后因素(HR 3.412,P=0.002 和 HR 2.615,P=0.029)。

结论

CLDN12 表达降低预示着宫颈癌患者预后不良。新型抗-CLDN12 mAb 可能是评估不同癌症类型和其他疾病中 CLDN12 表达生物学相关性的有价值工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a86e/8038723/2fd2937768a6/ijms-22-03774-g001.jpg

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