AUTHOR=Chai Jie , Liu Xiangli , Hu Xinju , Wang Chunfang 

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

JOURNAL=Pathology and Oncology Research

VOLUME=29

YEAR=2023

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2023.1611224

DOI=10.3389/pore.2023.1611224

ISSN=1532-2807

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> We classified and enumerated circulating tumor cells in the blood of breast cancer patients by CTC-enriched <italic>in situ</italic> 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.</p><p><bold>Results:</bold> 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, <italic>p</italic> &lt; 0.001). High Claudin-4 expression was associated with a lower count of epithelial CTCs (E-CTCs) (3.4 vs. 5.0, <italic>p</italic> = 0.033), higher counts of mesenchymal CTCs (M-CTC) (4.4 vs. 1.1, <italic>p</italic> &lt; 0.001), and epithelial/mesenchymal CTCs (E/M-CTCs) (4.0 vs. 3.5, <italic>p</italic> = 0.021). The intensity of Claudin-4 was positively correlated with CTC (r<sub>s</sub> = 0.43, <italic>p</italic> = 0.001). Multivariate COX regression analysis showed that CTC counts (HR = 1.3, <italic>p</italic> &lt; 0.001), Claudin-4 (HR = 4.6, <italic>p</italic> = 0.008), and Lymphatic metastasis (HR = 12.9, <italic>p</italic> = 0.001) were independent factors for poor prognosis. COX regression of CTC classification showed that epithelial/mesenchymal CTCs (E/M-CTC) (HR = 1.9, <italic>p</italic> = 0.001) and mesenchymal CTCs (M-CTC) (HR = 1.5, <italic>p</italic> = 0.001) were independent influencing factors of adverse reactions in breast cancer patients.</p><p><bold>Conclusion:</bold> 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.</p>