Abstract

It is aimed at investigating the changes of serum soluble programmed death-ligand 1 (sPD-L1) expression level in nonsmall cell lung cancer (NSCLC) before and after radiotherapy, the correlation of PD-L1, PD-1, and proteins of Akt (protein kinase B), mTOR, and HIF-1α, and the molecular mechanism of the PD-1/PD-L1 pathway in the development of NSCLS. A total of 126 NSCLC patients receiving radiotherapy in Liaoning Cancer Hospital from September 2018 to September 2019 were selected as the observation group, and another 58 healthy volunteers were selected as the control group. NSCLC patients were divided into group A (stage I-II, stereotactic radiotherapy) and group B (stage III, intensity-modulated radiation therapy) according to the cancer stage. The efficacy of radiotherapy was evaluated, and sPD-L1 expression was detected by ELISA. The immunohistochemical staining was adopted to detect protein expressions of Akt, mTOR, and HIF-1α in NSCLC tissues. The correlation between their expression and expression of PD-L1 and PD-1 was analyzed. The results showed that the overall response rate (ORR) of group A was 89.29%, the clinical benefit response (CBR) was 96.43%, the median survival time (MST) was 25 months, and the survival rate within three years was 72.56%. In group B, the ORR was 70.41%, the CBR was 97.96%, the MST was 18 months, and the survival rate within three years was 34.67%. Comparison of overall serum sPD-L1 expression in the control group, group A, and group B and between groups before radiotherapy was statistically significant (P < 0.01). After radiotherapy, serum sPD-L1 expression in group A and group B decreased compared with that before radiotherapy (P < 0.01). Among NSCLC patients, the positive expression rate of Akt, mTOR, and HIF-1α was 71.32%, 41.26%, and 80.65%, respectively. PD-L1 expression and Akt, mTOR, and HIF-1α expression showed a significant correlation. PD1 expression and Akt, mTOR, and HIF-1α expression also showed a significant correlation. It indicated that the expression level of sPD-L1 in NSCLC patients was higher than that in normal subjects, but the expression level of sPD-L1 was decreased after radiotherapy. PD-1/PD-L1 may play important roles in NSCLC procession through the Akt/mTOR and HIF-1α pathway.

Highlights

  • With the improvement of the economic and the deteriorating living environment, malignant tumors have surpassed cardiovascular diseases as the primary cause of harm to human life and health [1]

  • A total of 126 nonsmall cell lung cancer (NSCLC) patients receiving radiotherapy in Liaoning Cancer Hospital from September 2018 to September 2019 were selected as the observation group, and another 58 healthy volunteers were selected as the control group

  • The expression of progression of disease (PD)-L1 and PD1 was both significantly correlated with the expression of Akt, mTOR, and HIF-1α, indicating that PD-1/PD-L1 may play an important role in the pathogenesis of NSCLC through Akt/mTOR and HIF-1α pathways, but the related mechanisms still needed to be further studied

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Summary

Introduction

With the improvement of the economic and the deteriorating living environment, malignant tumors have surpassed cardiovascular diseases as the primary cause of harm to human life and health [1]. The incidence and mortality of lung cancer rank first among malignant tumors [2]. The main clinical treatments for NSCLC include surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, and traditional Chinese medicine [4, 5]. Surgery and chemotherapy are usually suitable for the early stages of NSCLC, but usually, 80% of patients are already in the middle and advanced stages when they are diagnosed. The advanced treatment of NSCLC usually adopts chemotherapy or targeted therapy. The survival rate of patients in five years after chemotherapy is only 2%, the median survival time is 10 months, and the prognosis effect is poor. Radiotherapy is a local treatment method for tumors, which can be used in different stages and different

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