A total of 31 proteins were associated with prostate cancer risk including proteins encoded by <i>GSTP1</i>, whose methylation level was shown previously to be associated with prostate cancer risk, and <i>MSMB, SPINT2, IGF2R</i>, and <i>CTSS</i>, which were previously implicated as potential target genes of prostate cancer risk variants identified in genome-wide association studies.
The results together indicate that HAI-2 is a cognate inhibitor of matriptase, and KD1 of HAI-2 plays a major role in the inhibition of cellular matritptase activation as well as human prostate cancer invasion.
A reduction in SPINT2 expression levels from non-neoplastic to PCa tissues was observed; however, none of the cases exhibited SPINT2 promoter methylation.
The expression level and activity of matriptase increased whereas the HAI-2 protein level decreased over the course of orthotopic tumor growth in mice, which was consistent with the immunohistochemical profiles of matriptase and HAI-2 in archival PCa specimens.