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

## TL;DR

The biomarker hPG80 increases in current smokers but returns to normal after quitting, and it can also detect lung cancer in non-COPD former smokers.

## Contribution

hPG80 is shown to be a reversible smoking marker and a potential early diagnostic tool for lung cancer.

## Key findings

- hPG80 levels in current smokers are significantly higher than in never smokers.
- hPG80 levels return to normal in former smokers, independent of COPD status.
- hPG80 shows strong diagnostic accuracy for lung cancer in former smokers.

## Abstract

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.

The online version contains supplementary material available at 10.1186/s40364-025-00861-4.