In this study, we applied complementary analytical techniques; 1H HR MAS NMR on intact PC tissues, followed by liquid 1H NMR, 31P NMR spectroscopy and LC-MS on tissue extracts to explore metabolic alterations during PC development and disease progression from lower to higher GS and between TMPRSS2-ERG-positive and -negative PC. Here, TMPRSS2 is linked to pachyonychia congenita.