Expression levels of key components of Hedgehog pathway and investigating the correlation of this pathway with the expression levels of Claudin-1 in invasive breast carcinoma

Objective and Breast cancer is considered as a heterogeneous disease, characterized by different biological and phenotypic features which make its diagnosis and treatment challenging. Here we sought to investigate the expression levels of key components of Hedgehog signaling pathway and correlation between the signal transducer Smo and some clinicopathological features such as lymph node metastasis and metastasis stage in invasive breast carcinoma. Also, the inverse correlation between the expression levels of Smo and Claudin-1 (an important gene involved in cell tight junctions) was studied.
In this case-control study, among 36 pairs of specimens, tumor tissues and their adjacent normal ones from patients with Invasive ductal breast carcinoma, the expression levels of Key components of Hedgehog signaling (Smo, Gli1 and Ptch), Claudin-1, E-cadherin, and MMP2 were measured by Q-RT-PCR. Also, the correlation of Smo expression with some clinicopathologic parameters was analyzed.
We found up-regulation of Hedgehog signaling in invasive breast carcinoma samples compared to normal adjacent tissues. Moreover, upregulation of the signal transducer Smo was correlated with tumor stages and lymph node metastasis of breast tumor. Interestingly, this correlation was affected by the expression of Her2. There is also a significant correlation between the expression levels of the signal transducer Smo and Claudin-1 (A gene involved in tight junctions), E-cadherin (Epithelial cell marker), and MMP2 (metastasis-related gene) in tumor samples with advanced stages of metastasis.
Taken together, our study revealed a new layer of molecular complexity which should be considered in the management of patients with invasive breast carcinoma. The results suggest a key role for Hedgehog signaling in invasive breast carcinoma. Also, regarding the inverse correlation between expression levels of Claudin-1 and Hedgehog signaling, it seems that Claudin-1 could serve as a diagnostic biomarker; however, its clinical significance remains to be further clarified.