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Molecular Mechanism of Expression Changes of Immunological Indexes of PD-1/sPD-L1 after Radiotherapy in Nonsmall Cell Lung Cancer

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 t...

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Published in:BioMed research international 2021-04, Vol.2021, p.8811751-8
Main Authors: Qu, Yanli, Wang, Huan, Liu, Hangyu, Sun, Xiaohu, Li, Ji, Yu, Hong
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Wang, Huan
Liu, Hangyu
Sun, Xiaohu
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Yu, Hong
description 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
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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&lt;0.01). After radiotherapy, serum sPD-L1 expression in group A and group B decreased compared with that before radiotherapy (P&lt;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. 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This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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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&lt;0.01). After radiotherapy, serum sPD-L1 expression in group A and group B decreased compared with that before radiotherapy (P&lt;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. 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Wang, Huan ; Liu, Hangyu ; Sun, Xiaohu ; Li, Ji ; Yu, Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c476t-a3349d4695ac4a7ec1baf91ddb41ff5d3bdd7a2d787894ce4567e958d1ef0b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>AKT protein</topic><topic>Apoptosis</topic><topic>B7-H1 Antigen - blood</topic><topic>B7-H1 Antigen - metabolism</topic><topic>Cancer therapies</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - radiotherapy</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>Cell receptors</topic><topic>Cellular signal transduction</topic><topic>Chemotherapy</topic><topic>Correlation</topic><topic>Development and progression</topic><topic>Disease</topic><topic>Drinking water</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Enzymes</topic><topic>Ethanol</topic><topic>Female</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hypoxia-inducible factor 1a</topic><topic>Immunology</topic><topic>Kinases</topic><topic>Lung - chemistry</topic><topic>Lung - pathology</topic><topic>Lung cancer</topic><topic>Lung cancer, Non-small cell</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - radiotherapy</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Non-small cell lung carcinoma</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Programmed Cell Death 1 Receptor - blood</topic><topic>Programmed Cell Death 1 Receptor - metabolism</topic><topic>Protein biosynthesis</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Radiation</topic><topic>Radiation therapy</topic><topic>Radiotherapy</topic><topic>Statistical analysis</topic><topic>Surgery</topic><topic>Survival</topic><topic>T cell receptors</topic><topic>TOR protein</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qu, Yanli</creatorcontrib><creatorcontrib>Wang, Huan</creatorcontrib><creatorcontrib>Liu, Hangyu</creatorcontrib><creatorcontrib>Sun, Xiaohu</creatorcontrib><creatorcontrib>Li, Ji</creatorcontrib><creatorcontrib>Yu, Hong</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; 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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&lt;0.01). After radiotherapy, serum sPD-L1 expression in group A and group B decreased compared with that before radiotherapy (P&lt;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.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>33987445</pmid><doi>10.1155/2021/8811751</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7533-6815</orcidid><oa>free_for_read</oa></addata></record>
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subjects Aged
AKT protein
Apoptosis
B7-H1 Antigen - blood
B7-H1 Antigen - metabolism
Cancer therapies
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - mortality
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Non-Small-Cell Lung - radiotherapy
Care and treatment
Case-Control Studies
Cell receptors
Cellular signal transduction
Chemotherapy
Correlation
Development and progression
Disease
Drinking water
Enzyme-linked immunosorbent assay
Enzymes
Ethanol
Female
Health aspects
Humans
Hypoxia-inducible factor 1a
Immunology
Kinases
Lung - chemistry
Lung - pathology
Lung cancer
Lung cancer, Non-small cell
Lung Neoplasms - metabolism
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Lung Neoplasms - radiotherapy
Male
Medical prognosis
Middle Aged
Non-small cell lung carcinoma
Patient outcomes
Patients
PD-1 protein
PD-L1 protein
Programmed Cell Death 1 Receptor - blood
Programmed Cell Death 1 Receptor - metabolism
Protein biosynthesis
Protein kinases
Proteins
Radiation
Radiation therapy
Radiotherapy
Statistical analysis
Surgery
Survival
T cell receptors
TOR protein
Tumors
title Molecular Mechanism of Expression Changes of Immunological Indexes of PD-1/sPD-L1 after Radiotherapy in Nonsmall Cell Lung Cancer
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