The lung cancer-associated blood biomarker hPG80 exhibits a reversible increase in response to smoking in asymptomatic individuals

The blood biomarker hPG₈₀ is linked to multiple solid tumors, including lung cancer. This study examined blood hPG₈₀ levels of asymptomatic individuals and patients with non-small cell lung cancer (NSCLC), categorized by their smoking and chronic obstructive pulmonary disease (COPD) status. Plasma hPG₈₀ levels were measured across five cohorts of patients, including 396 NSCLC patients, 200 NSCLC cancer-free COPD patients, 369 asymptomatic never smokers, 278 asymptomatic current smokers, and 235 asymptomatic former smokers. Receiver operating characteristic (ROC) curves assessed diagnostic accuracy. In asymptomatic current smokers, hPG₈₀ levels were significantly higher (6.70 pM (IQR: 5.13-11.29)) than those in gender- and age-matched never smokers (2.50 pM (IQR: 1.70-3.70; p < 0.0001). In contrast, gender- and age-matched former smokers showed a return to normal hPG₈₀ levels (2.29 pM (IQR: 1.61-2.97)). In multivariate analysis, age and smoking status were significantly associated with elevated levels of hPG₈₀ (p-values of 0.0319 and < 0.0001, respectively). Levels of hPG₈₀ in current smokers were not different from levels found in age-matched patients with NSCLC or COPD (6.60 pM (IQR: 4.36-11.22) and 6.07 pM (IQR: 3.99-11.69), respectively). In NSCLC and COPD patients, hPG₈₀ levels were independent of the smoking status. When comparing asymptomatic and NSCLC-diagnosed former smokers, the AUC was 0.85 (95% CI:0.80-0.90, p < 0.0001). The AUC was equal to 0.53 (95% CI: 0.45-0.60, p = 0.4436) for current smokers. Our findings identify hPG₈₀ as both a reversible marker of active smoking and a diagnostic biomarker of NSCLC. This dual role supports its potential use in risk stratification and early detection, particularly among non-COPD former smokers.