Claudin-4 Expression Is Associated With Disease-Free Survival in Breast Carcinoma-in-Situ: Mean Follow-up of 8.2 Years

Duarte, Giuliano Mendes; Almeida, Natalie Rios; Tocchet, Fernando; Espínola, Juliana Pinho; Barreto, Carolina Teixeira de Resende; Pinto, Glauce Aparecida; Soares, Fernando Augusto; Marshall, Priscila Silva; Silva, Geisilene Russano de Paiva

doi:10.1016/j.clbc.2018.06.005

Cited by 8 publications

(5 citation statements)

References 21 publications

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“…Increased expression of CLDN4 enhances maintenance of the tumor microenvironment and stemness, while EMT reduces the expression . Thus, both correlation and inverse correlation have been reported for CLDN4 expression and prognosis . The results of this study suggest that in TNBC, enhanced CLDN4 expression is correlated with pathological prognostic factors, and CLDN4 expression levels are expected to be correlated with poor prognosis .…”

Section: Discussionsupporting

confidence: 52%

“…10 Thus, both correlation and inverse correlation have been reported for CLDN4 expression and prognosis. 32,33 The results of this study suggest that in TNBC, enhanced CLDN4 expression is correlated with pathological prognostic factors, and CLDN4 expression levels are expected to be correlated with poor prognosis. 32 CLDN4 was considered to be more suitable as a molecular target for TNBC.…”

Section: Discussionmentioning

confidence: 81%

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Targeting claudin‐4 enhances chemosensitivity in breast cancer

et al. 2020

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| INTRODUC TI ONBreast cancer is the third leading cause of cancer death in Japanese women. 1 The most common histological type, invasive ductal carcinomas (IDC), frequently express hormone receptors (luminal subtype) and/or human epidermal growth factor receptor-2 (HER2, Her2 subtype). 2,3 In contrast, approximately 15% of IDC express none of estrogen receptor (ER), progesterone receptor Abstract Triple negative breast cancer (TNBC) is characterized by highly aggressive phenotype, limited treatment options and a poor prognosis. In the present study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDC (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and was correlated with histological grade. In contrast, expression of CLDN4 was correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors and increased the intratumoral pH. Moreover, concurrent treatment with 4D3, PTX and tamoxifen, or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in a bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects. K E Y W O R D S breast cancer, chemotherapy, claudin, microenvironment, tight junction | 1841 LUO et aL.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 81%

Targeting claudin‐4 enhances chemosensitivity in breast cancer

et al. 2020

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“…Claudin-4 expression has prognostic value for some tumors. For example, overexpression of claudin-4 suggested shorter 5-year progression-free survival and overall survival of ovarian cancer [34], while low expression of claudin-4 indicated a shorter disease-free survival of breast carcinoma in situ [35].…”

Section: Analytical Cellular Pathologymentioning

confidence: 99%

Expression of Tight Junction Proteins Is Altered in Bladder Cancer

Chen

2020

Analytical Cellular Pathology

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Bladder cancer (BC) is one of the tumors which occur most frequently in urological system, but less is known about the expression of tight junction proteins and its clinical significance in BC. In this study, expression of claudin-4, zonula occludens-1 (ZO-1) and zonula occludens-1 nucleic acid-binding protein (ZONAB), in BC tissues, adjacent nontumor tissue (ANTT), and BC cell lines was examined by Western blotting, semiquantitative RT-PCR, and immunohistochemistry, and then, the clinical significance of these proteins was investigated. The mRNA and protein expression of ZONAB were significantly upregulated, while those of ZO-1 was significantly downregulated in some BC cell lines and tissues in comparison with nontumor urothelial cell lines and ANTT. High expression rate of ZO-1 and ZONAB had negative correlation in BC tissues and was also correlated with muscle-invasive lesions in BC tissues. In conclusion, the expression of tight junction proteins is significantly altered in BC and ZO-1, and ZONAB interaction might be involved in BC development.

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“…Therefore, Claudin-4 plays an important role in the occurrence and metastasis of cancer cells [ 18 ]. Studies have shown that Claudin-4 is highly expressed in various malignant tumors [ 19 ], suggesting that Claudin-4 may become a tumor marker and an emerging target for treatment [ 20 – 22 ]. Claudin-4 has been reported to regulate EMT through p21-activated kinase 4 (PAK4) expression in human breast cancer cells [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Correlation analysis of circulating tumor cells and Claudin-4 in breast cancer

Chai¹,

Liu²,

Hu³

et al. 2023

Pathol. Oncol. Res.

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Objective: We aimed to explore the relationship between peripheral blood circulating tumor cells (CTCs) and the expression of Claudin-4 in patients with breast cancer, and further explore the potential impact on clinical prognosis and risk assessment.Methods: We classified and enumerated circulating tumor cells in the blood of breast cancer patients by CTC-enriched in situ hybridization and the detection of Claudin-4 expression by immunohistochemistry. We carried out an analysis of the correlation between the two and the comparison of their impact on clinical parameters and prognosis.Results: There were 38 patients with a low expression of Claudin-4 and 27 patients with a high expression of Claudin-4. Compared with Claudin-4 low-expression patients, the number of CTCs was higher in patients with high Claudin-4 expression (11.7 vs. 7.4, p < 0.001). High Claudin-4 expression was associated with a lower count of epithelial CTCs (E-CTCs) (3.4 vs. 5.0, p = 0.033), higher counts of mesenchymal CTCs (M-CTC) (4.4 vs. 1.1, p < 0.001), and epithelial/mesenchymal CTCs (E/M-CTCs) (4.0 vs. 3.5, p = 0.021). The intensity of Claudin-4 was positively correlated with CTC (rs = 0.43, p = 0.001). Multivariate COX regression analysis showed that CTC counts (HR = 1.3, p < 0.001), Claudin-4 (HR = 4.6, p = 0.008), and Lymphatic metastasis (HR = 12.9, p = 0.001) were independent factors for poor prognosis. COX regression of CTC classification showed that epithelial/mesenchymal CTCs (E/M-CTC) (HR = 1.9, p = 0.001) and mesenchymal CTCs (M-CTC) (HR = 1.5, p = 0.001) were independent influencing factors of adverse reactions in breast cancer patients.Conclusion: The number of CTC in breast cancer is positively correlated with the expression of Claudin-4. High CTC counts and a high proportion of M-CTCs correlated with Claudin-4 expression. CTC counts and Claudin-4 expression were independent predictors of poor prognosis in breast cancer patients.

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Claudin-4 Expression Is Associated With Disease-Free Survival in Breast Carcinoma-in-Situ: Mean Follow-up of 8.2 Years

Cited by 8 publications

References 21 publications

Targeting claudin‐4 enhances chemosensitivity in breast cancer

Targeting claudin‐4 enhances chemosensitivity in breast cancer

Expression of Tight Junction Proteins Is Altered in Bladder Cancer

Correlation analysis of circulating tumor cells and Claudin-4 in breast cancer

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