Elevated Circulatory Proline to Glutamine Ratio (PQR)\nin Endometriosis and Its Potential as a Diagnostic Biomarker

Endometriosis (EM)\nis a hormone-dependent gynecological disease\nassociated with chronic pelvic pain and altered immuno-inflammatory\nprocesses. It shares some cancer-like characteristics such as increased\nproline biosynthesis and activated glutaminolysis. Both proline and\nglutamine are interconvertible metabolically, and studies have shown\ntheir roles in cancer cell metabolic reprogramming, redox homeostasis,\noccurrence/development of endometrial carcinoma, and its further progression\ntoward the malignant state. So based on this, we hypothesized that\nthe circulatory proline to glutamine ratio (PQR) would be altered\nin EM and may serve as an indicative biomarker to improve the clinical\ndiagnosis of EM. In present study, the circulatory-PQR levels were\nestimated for 39 EM patients and 48 age matched healthy female subjects\nusing 800 MHz NMR spectroscopy. Among 39 EM patients, 15 were in the\nclinical stages I to II and referred to here as moderate EM (MEM)\npatients and 24 were in the clinical stages III to IV and referred\nhere as severe EM (SEM) patients. The circulatory-PQR levels were\nsignificantly increased in EM patients (0.99 ± 0.13 μM\nin MEM; 1.39 ± 0.22 μM in SEM) compared to normal control\n(NC) subjects (0.52 ± 0.05 μM in NC). Further, the circulatory\nPQR levels exhibit the highest diagnostic potential with area under\nreceiver operating characteristic (AUROC) curve values equal to 0.87\n± 0.04 [95%CI = 0.79–0.96] for MEM and 0.89 ± 0.04\n[95% CI = 0.82–0.96] for SEM. These results suggested that\ncirculatory-PQR has significant potential to serve as a noninvasive\nbiomarker for diagnostic/prognostic screening of EM and further underscored\nthe importance of these two nonessential amino acids (proline and\nglutamine) in cancer metabolism.