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

Jie Chai; Xiangli Liu; Xinju Hu; Chunfang Wang

doi:10.3389/pore.2023.1611224

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

Pathol Oncol Res. 2023 Jul 3:29:1611224. doi: 10.3389/pore.2023.1611224. eCollection 2023.

Authors

Jie Chai¹, Xiangli Liu¹, Xinju Hu¹, Chunfang Wang²

Affiliations

¹ Pathology Department, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
² Breast Surgery, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.

Abstract

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 (r_s = 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.

Keywords: breast cancer; circulating tumor cells; claudin-4; molecular subtype; tight junction protein.

MeSH terms

Biomarkers, Tumor / metabolism
Breast Neoplasms* / pathology
Claudin-4
Female
Humans
Neoplastic Cells, Circulating* / pathology
Prognosis

Substances

Claudin-4
Biomarkers, Tumor