Circulating PCSK9: A new frontier in cancer risk stratification for obese diabetics

This study investigated potential plasma biomarkers associated with cancer risk and mortality in patients with type 2 diabetes mellitus (T2DM), a population known to have an increased cancer incidence and poorer outcomes compared with non-diabetic individuals. Traditional metabolic indicators, including blood pressure, blood glucose and blood lipids, have limited predictive value for cancer risk, highlighting the need for novel clinical biomarkers. In total, 141 subjects with T2DM were enrolled in this study. Plasma inflammatory and lipid-related biomarkers included cluster of differentiation 147 (CD147), cyclophilin A (CyPA), cytokines, oxidized low-density lipoprotein (oxi-LDL), oxi-LDL antibody and proprotein convertase subtilisin/kexin type 9 (PCSK9). Among all participants, 37.6% were obese (body mass index ≥27 kg/m²). During 10 years of follow-up, all-cause mortality reached 35% and cancer incidence was 16%. Obese diabetic patients exhibit elevated oxi-LDL, soluble intercellular adhesion molecule-1, PCSK9, CD147 and CyPA levels. Deceased patients had a higher incidence of cancer and significantly lower plasma CD147 levels than surviving patients. Receiver operating characteristic curve analysis identified PCSK9 as a potential predictor of cancer occurrence in obese individuals with T2DM [area under the curve (AUC)=0.726], whereas CD147 showed modest predictive value in non-obese patients with diabetes (AUC=0.665). These findings suggest that plasma PCSK9 and CD147 may be associated with cancer occurrence in specific subgroups of patients with T2DM. However, larger prospective studies are required to confirm these associations and to further evaluate their potential value in cancer risk assessment.