The ratio of Matriptase/HAI-l mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals

Background: It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatically increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression. The aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine at which stages a dysregulated ratio of matriptase/ HAI-1 mRNA is present during carcinogenesis. Methods: Using quantitative RT-PCR, we have determined the mRNA levels for matriptase and HAI-1 in colorectal cancer tissue ( n = 9), severe dysplasia ( n = 15), mild/moderate dysplasia ( n = 21) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers ( n = 10). Matriptase and HAI-1 mRNA levels were normalized to beta-actin. Results: Matriptase mRNA level was lower in carcinomas compared to normal tissue from healthy individuals ( p < 0.01). In accordance with this, the matriptase mRNA level was also lower in adenomas/carcinomas combined as compared to their adjacent normal tissue ( p < 0.01). HAI-1 mRNA levels in both normal and affected tissue from individuals with severe dysplasia or carcinomas and in affected tissue with mild/moderate dysplasia were all significantly lower than mRNA levels observed in corresponding tissue from healthy control individuals. HAI-1 mRNA was lower in carcinomas as compared to normal tissue from healthy individuals ( p < 0.001). HAI-1 mRNA levels were significantly lower in tissue displaying mild/moderate ( p < 0.001) and severe ( p < 0.01) dysplasia compared to normal tissue from the same patients. Both adenomas and carcinomas displayed a significantly different matriptase/ HAI-1 mRNA ratio than corresponding normal tissue from healthy control individuals ( p < 0.05). In addition statistically significant difference ( p < 0.001) could be observed between mild/moderate and severe adenomas and their adjacent normal tissue. Conclusion: Our results show that dysregulation of the matriptase/ HAI-1 mRNA ratio occurs early during carcinogenesis. Future studies are required to clarify whether the dysregulated matriptase/ HAI-1 ratio was causing the malignant progression or is a consequence of the same.