Background: Survival in non-small cell lung cancer (NSCLC) remains poor. Early detection of NSCLC is of great significance to provide a chance to improve survival. Aim: We constructed predictive models to evaluate the predictive value of four tumor biomarkers by including serum human epididymis protein 4 (HE4), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), and cytokeratin 19 fragment (CY21-1) on detecting NSCLC in a Chinese elderly population. Methods: A total of 363 patients with NSCLC and 433 subjects without cancer (healthy control group) were admitted to the respiratory department in our hospital. We assessed serum levels of these four tumor biomarkers in the two groups and then the predictive value of predictive models was evaluated. Results: Serum median values of HE4 (143.3 pmol/L), CEA (4.60 ng/mL), SCCA (1.52 ng/ mL), and CY21-1 (5.36 ng/mL) in patients with NSCLC were significantly higher than the healthy control group, respectively (all P<0.05). A multivariate logistic regression model showed that HE4 (OR=2.10, 95% CI=1.22-4.42, P=0.013), CEA (OR=2.30, 95% CI=1.44-4.53, P=0.004), SCCA (OR=2.20, 95% CI=1.29-4.55, P=0.011), and CY21-1 (OR=2.60, 95% CI=1.56-6.25, P<0.001) were significantly and independently associated with increased risk of NSCLC on admission after confounding factors were corrected. Importantly, the ROC curve suggested HE4 had a good value on predicting NSCLC in the Chinese elderly population. Additionally, the predictive model (CEA+SCCA+CY21-1+HE4) had better idea capability to detecting the existence of NSCLC (AUC=0.954, 95% CI=0.927-0.999, P<0.001). Conclusion:Our study showed that several lung cancer-related biomarkers were used to build prediction models, which has good value for early prediction of NSCLC.

This study examined the effects of the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count after pulmonary infection. Sprague‒Dawley rats were subjected to tracheal injection of lipopolysaccharide (LPS) to establish animal models of pulmonary infection. By inhibiting the PI3K/AKT pathway or inhibiting/inducing mitochondrial autophagy in macrophages, the severity of the pulmonary infection and the leukocyte count were altered. The PI3K/AKT inhibition group did not show a significant difference in leukocyte counts compared with the infection model group. Mitochondrial autophagy induction alleviated the pulmonary inflammatory response. The infection model group had significantly higher levels of LC3B, Beclin1, and p-mTOR than the control group. The AKT2 inhibitor group exhibited significantly increased levels of LC3B and Beclin1 compared with the control group (P < 0.05), and the Beclin1 level was significantly higher than that in the infection model group (P < 0.05). Compared with the infection model group, the mitochondrial autophagy inhibitor group exhibited significantly decreased levels of p-AKT2 and p-mTOR, whereas the levels of these proteins were significantly increased in the mitochondrial autophagy inducer group (P < 0.05). PI3K/AKT inhibition promoted mitochondrial autophagy in macrophages. Mitochondrial autophagy induction activated the downstream gene mTOR of the PI3K/AKT pathway, alleviated pulmonary inflammatory reactions, and decreased leukocyte counts.