MMP7 sensitivity of mutant ECM proteins: An indicator of melanoma survival rates and T-cell infiltration.

OBJECTIVE: To assess the potential impact of mutant ECM amino acids (AA) on melanoma-related matrix metalloproteinase-7 (MMP7) activity. DESIGN AND METHODS: We applied a novel scripted algorithm, based on the MEROPS database, to reveal mutant-dependent sensitivity changes across the cancer genome atlas, melanoma dataset. RESULTS: This approach revealed a strong bias in favor of mutant AA dependent protease sensitivity increases. Thus, melanoma specimens with relatively few mutations had only MMP7 mutant sensitive, ECM peptides. As mutations increased, melanoma specimens included mutant AA representing mostly increased sensitivity and a small but increasing number of mutant AA representing decreased MMP7 sensitivity. There was no detection of melanoma specimens with only decreases in MMP7 sensitivity. Furthermore, melanoma specimens with exclusively increased sensitivity and thereby only a few overall mutations represented reduced T-cell infiltrates and worse outcomes. CONCLUSIONS: Overall, the results indicated that changes in MMP7 sensitivity, attributable to mutant AA, have the potential of identifying patients with distinct survival outcomes as well as patients with cancer specimen immune activity.