Dataset Information

Prognostic Significance of Aberrant Claudin-6 Expression in Endometrial Cancer.

ABSTRACT: Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer. The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, p = 0.014). It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.

SUBMITTER: Kojima M

PROVIDER: S-EPMC7656298 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Prognostic Significance of Aberrant Claudin-6 Expression in Endometrial Cancer.

Kojima Manabu M Sugimoto Kotaro K Tanaka Mizuko M Endo Yuta Y Kato Hitomi H Honda Tsuyoshi T Furukawa Shigenori S Nishiyama Hiroshi H Watanabe Takafumi T Soeda Shu S Fujimori Keiya K Chiba Hideki H

Cancers 20200924 10

<h4>Background</h4>Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer.<h4>Results</h4>The established mAb selectively ...[more]

PMID: 32987797

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Project description:ObjectiveCervical cancer is one of the leading fatal diseases in women, and the role of Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) in cervical cancer is uncertain.MethodsFour Gene Expression Omnibus (GEO) mRNA microarray datasets were analyzed to identify differentially expressed genes (DEGs) between cervical cancer and normal cervical tissues. The results were validated using a The Cancer Genome Atlas (TCGA)-cervical cancer (CESC) dataset. Expression profiles and patients' clinical data were used to investigate the relationship between APOBEC3B expression and cervical cancer survival. APOBEC3B co-expressed genes were subjected to enrichment analyses, and correlations between APOBEC3B expression and immunologic infiltrates were investigated using Tumor Immune Estimation Resource (TIMER). We generated receiver operating characteristic curve (ROC) curves to evaluate the performance of APOBEC3B expression in predicting cervical cancer prognosis.ResultsFourteen overlapping DEGs were obtained, and APOBEC3B was chosen as a candidate gene. TCGA data further confirmed that APOBEC3B was significantly increased in cervical cancer, relative to normal adjacent tissues, and this expression was associated with poor clinical outcome. Results from quantitative real time polymerase chain reaction (RT-qPCR) and immunohistochemical staining of cervical carcinoma tissues supported these findings. Enrichment analysis showed that APOBEC3B co-expressed genes were mainly enriched in cell cycle, DNA replication and chromosomal region. Moreover, APOBEC3B expression was significantly associated with T stage, M stage, primary therapy outcome and poor clinical prognosis in cervical cancer. Similarly, APOBEC3B was closely correlated with gene markers of diverse immune cells. APOBEC3B expression was an independent indicator of cervical cancer prognosis, according to univariate Cox and ROC analyses.ConclusionHigh APOBEC3B expression is strongly related to a poor prognosis in cervical cancer patients.

Dataset Information

Prognostic Significance of Aberrant Claudin-6 Expression in Endometrial Cancer.

Publications

Prognostic Significance of Aberrant Claudin-6 Expression in Endometrial Cancer.

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