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Introduction. Claudin-10 (CLDN10), a member of the Claudin tight junction (TJ) protein family, was initially known as Oligodendrocyte-Specific Protein-Like (OSP-L). The distribution of CLDN10 in the body is not ubiquitous and is seen more abundantly in kidney and brain and at modest levels in mammary tissues. Limited information suggests that in cells where CLDN10 is expressed, it interacts with other family members including CLDN-11, 12, 16, 17 and the subcoat zonula occludens (ZO-1 and ZO-3) to regulate TJ functions. The role played by CLDN10 in cancer is not clear but there are suggestions that it is a favourable indicator for disease progression in kidney and gastric cancers but an adverse indictor in hormone related cancers such as thyroid cancer. The role of CLDN10 in breast cancer is otherwise not known. We have investigated the expression profile and in particular in its relationship with hormone receptor status. Methods. We carried out CLDN10 transcript and protein analyses by way of quantitative PCR and immunohistochemistry on an established cohort of fresh frozen mammary tissues and breast cancer tissues. Expression was analysed via QPCR against the staging, histology, clinical outcome, hormone status including ER and Her family members, and also its known interactive TJ molecules available to our database. Results. Compared with its interactive TL partner molecules, CLDN10 was expressed at relatively low levels in mammary tissues. There was no significant difference in CLDN10 transcript levels between normal tissues and tumour tissues. Patients with high levels of CLDN10 in breast tumours had significantly shorter overall survival (OS) (p=0.041) and disease free survival (DFS) (p=0.026). In our cohort, we found a significant correlation between levels of CLDN10 and Her-1/EGFR (r=0.201, p=0.026) and Her3 (r=0.935, p< 0.0001), but not with Her-2 nor with Her-4. It was also surprised to find that CLDN10 did not correlated with the ZO-1, ZO-3, CLDN11, 12, 14, and 17. We then identified a subgroup of patients with low levels of CLDN10 and their overall survival (OS) and disease free survival (DFS) which were significantly correlated with Her-1/Her-3 expression status (p< 0.0001 for both OS and DFS). CLDN10, amongst the clinical, pathological and hormone receptor status, is an independent prognostic factor for DFS (p=0.008, Hazard Ratio (HR) =4.228 (95% CI 1.449-12.342)) and for OS (p=0.025, HR=3.917 (95% CI 1.187-12.924)). The predictive power for triple negative breast cancer (TNBC) and non-TNBC by CLDN10 otherwise remained similar and not statistically significant. It was noted that stratification by ER and Her-2 did not contribute to the value of independency. Conclusion. CLDN10, although expressed at relative lower levels in breast cancer, is a contributing factor to the survival of the patients. Together with the status of EGFR and Her-3, it makes an independent prognostic factor for both the overall survival and disease free survival of the patients. Citation Format: Xinguo Zhuang, Wen G. Jiang, Fiona Ruge, Eleri Davies, Bing Xu, Tracey A. Martin. The Expression of Claudin-10 in relationship with Her family members in patients with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-29. |
