Usability of serum hedgehog signalling proteins as biomarkers in canine mammary carcinomas

Abstract

Background The hedgehog signalling pathway has been implicated in tumourigenesis and progression of many tumour types. This pathway has recently emerged as a therapeutic target, and inhibitors of hedgehog signalling have gained considerable attention. In dogs, the roles of hedgehog signals in several types of tumours have been investigated, but their relationship with canine mammary gland tumours (MGTs) has not been established. This study aimed to evaluate the expression of sonic hedgehog (SHH) and glioma-associated oncogene 1 (GLI-1) in the serum and mammary tumour tissues of dogs.

Results SHH and GLI-1 protein expression levels were significantly higher in MGT tissues than in normal mammary gland tissues, as well as in malignant MGT specimens than in benign MGT specimens. Serum levels of SHH and GLI-1 were higher in MGT patients than in healthy controls (p < .001 and .001, respectively). Serum SHH level showed a statistically significant relationship with metastatic status (p = .01), and serum GLI-1 level showed a statistically significant relationship with histologic grade (p = 0.048) and metastatic status (p = 0.007). Serum hedgehog signalling protein levels were not significantly associated with breed size, sex, tumour size, or histologic type.

Conclusions Hedgehog signalling protein expression in canine MGT tissue and serum differed according to the histological classification (benign and malignant) and metastatic status, indicating a relationship between the hedgehog signalling pathway and canine MGT. Thus, the hedgehog signalling pathway may serve as a new biomarker and therapeutic target in canine MGT patients.