Role of Sonic Hedgehog Ligand (SHH) in Gastric Cancer therapeutics.

Abstract

 Background: The hedgehog pathway ligand, Sonic Hedgehog (SHH) is the most well-studied and potent ligand of this particular pathway. Aberrant hedgehog signaling has been implicated in the development of different malignancies like brain and lung. In current study we are aimed to find out whether SHH expression might also be important in human gastric cancer development. Furthermore we correlated SHH expression with histopathological and clinical data to evaluate whether SHH could represent a new prognostic marker in gastric cancer treatment.

Materials and Methods:  53 patients with Gastric cancer were studied. Among them qRT PCR was performed on 45 samples & IHC was done on 53 samples. Protein expression & localization was quantified by immunohistochemistry. Protein expression levels in tissue specimens were scored and correlations were analyzed.

Results: Among 45 GC cases taken for mRNA expression (27/45) 60% showed over expression of SHH mRNA when compared to their adjacent normal tissues. Out of 53 GC cases, a total of 23/53 (43.39%) cases showed over expression of SHH protein as compared to their adjacent normal tissues and the rest 30/53 (56.60%) showed a normal-like pattern. Immunohistochemical analysis of SHH protein revealed abundant cytoplasmic localisation in almost all the tissue sections.

Conclusion: Our data indicate that activation of the hedgehog pathway, through overexpression of sonic hedgehog, may involve tumor progression and metastasis of gastric cancer. Thus, targeted inhibition of hedgehog signaling by inhibiting sonic hedgehog may have significant implications of gastric cancer therapeutics.