Abstract
Objectives
Due to lack of effective biomarkers for non-small cell lung cancer (NSCLC), many patients are diagnosed at an advanced stage, which leads to poor prognosis. Dysregulation of N6-methyladenosine (m6A) RNA contributes significantly to tumorigenesis and tumor progression. However, the diagnostic value of m6A RNA status in peripheral blood to screen NSCLC remains unclear.
Methods
Peripheral blood samples from 152 NSCLC patients and 64 normal controls (NCs) were applied to assess the m6A RNA levels. Bioinformatics and qRT-PCR analysis were performed to identify the specific immune cells in peripheral blood cells and investigate the mechanism of the alteration of m6A RNA levels.
Results
Robust elevation of m6A RNA levels of peripheral blood cells was exhibited in the NSCLC group. Moreover, the m6A levels increased as NSCLC progressed, and reduced after treatment. The m6A levels contained area under the curve (AUC) was 0.912, which was remarkably greater than the AUCs for CEA (0.740), CA125 (0.743), SCC (0.654), and Cyfra21-1 (0.730). Furthermore, the combination of these traditional biomarkers with m6A levels elevated the AUC to 0.970. Further analysis established that the expression of m6A erasers FTO and ALKBH5 were both markedly reduced and negatively correlated with m6A levels in peripheral blood of NSCLC. Additionally, GEO database and flow cytometry analysis implied that FTO and ALKBH5 attributes to peripheral CD4+ T cells proportion and activated the immune functions of T cells.
Conclusions
These findings unraveled that m6A RNA of peripheral blood immune cells was a prospective biomarker for the diagnosis of NSCLC.
Funding source: Guangdong Basic and Applied Basic Research Foundation
Award Identifier / Grant number: 2019A1515011318
Award Identifier / Grant number: 2021A1515110094
Funding source: Key Medical and Health Projects of Zhongshan City
Award Identifier / Grant number: 2020K0012
Funding source: the National Nature Science Foundation of China
Award Identifier / Grant number: 81900775
Award Identifier / Grant number: 81902693
Award Identifier / Grant number: 81901557
Funding source: Department of Education of Guangdong Province
Award Identifier / Grant number: 2017KTSCX155
Funding source: the Science Foundation of Guangzhou First People’s Hospital
Award Identifier / Grant number: KYQD0046
Award Identifier / Grant number: Q2019004
Funding source: General project of Shenzhen Science and Technology Innovation Commission
Award Identifier / Grant number: JCYJ20220530145003008
Funding source: Guangzhou Science and Technology Project
Award Identifier / Grant number: 202102020955
Acknowledgments
We appreciated Professor Jinye Xie for kindly providing peripheral blood samples of healthy people from Zhongshan People’s Hospital.
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Research funding: This study was supported by the fund from the National Nature Science Foundation of China (81900775; 81902693; 81901557); Educational Commission of Guangdong Province (2017KTSCX155); Guangdong Basic and Applied Basic Research Foundation (2019A1515011318; 2021A1515110094); the Science Foundation of Guangzhou First People’s Hospital (Q2019004; KYQD0046); Key Medical and Health Projects of Zhongshan City (2020K0012); General project of Shenzhen Science and Technology Innovation Commission (JCYJ20220530145003008) and Guangzhou Science and Technology Project (202102020955).
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Author contributions: HZJ, JP, and XY conceived and designed this study. YHF, HHH, YP and LWH collected the samples and performed the experiments. NSQ and CXC contributed to the data analysis. All authors contributed to the article and approved the submitted version.
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Competing interests: The authors declare no conflict of interest.
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Informed consent: Written informed consent was obtained from the individuals for the publication of any potentially identifiable images or data included in this article.
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Ethical approval: The Institutional Review Board of The Third Affiliated Hospital of Guangzhou Medical University approved this retrospective study (IRB number: S2021-114) on 20 March 2020.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2022-1033).
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