Circulating levels of high mobility group box-1 and nucleophosmin/B23 proteins and clinical significance in debut non-small cell lung cancer patients.

Alarmins are endogenous molecules that alert the immune system to circumvent the invading antigens in the host. Here, we investigated the serum levels of the high mobility group box 1 (HMGB-1) and nucleophosmin alarmins in a cohort of 162 newly diagnosed patients with non-small cell lung cancer and 60 age-matched healthy individuals. Interestingly, patients exhibited lower median values of HMGB-1 than healthy individuals, but higher levels of HMGB-1 were associated with a tumor size of > 2.0 cm. In addition, nucleophosmin levels were significantly increased in patients compared with healthy individuals, and those with tumors of > 2 cm in diameter also displayed higher circulating nucleophosmin levels. Furthermore, a strong association was reported between HMGB-1 and nucleophosmin levels in patients (r = 0.679; P = 0.0001) compared with healthy individuals. Interestingly, the strongest association between both alarmins was observed in patients with a Spread Through Airspaces pattern and tumors of less than 2 cm in size (r = 0.900; P = 0.0001). Co-expression of both alarmins was also observed in tumor tissues, although to a lesser extent. Altogether, our data indicate that high levels of each alarmin were individually associated with larger tumor size, however the most significant associations between both alarmins in NSCLC seemed to be primarily linked to early disease progression parameters. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-43471-2.