Increased levels of N6-methyladenosine in peripheral blood RNA: a perspective diagnostic biomarker and therapeutic target for non-small cell lung cancer

作者：Yin, Haofan; Hong, Honghai; Yin, Ping; Lu, Wenhua; Niu, Shiqiong; Chen, Xinchun; Xia, Yong^*; Jiang, Ping^*; Huang, Zhijian^*

来源：Clinical Chemistry and Laboratory Medicine, 2023, 61(3): 473-484.

DOI：10.1515/cclm-2022-1033

• N6-methyladenosine
• biomarker
• non-small cell lung cancer
• peripheral blood
• therapeutic target

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 (m(6)A) RNA contributes significantly to tumorigenesis and tumor progression. However, the diagnostic value of m(6)A 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 m(6)A 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 m(6)A RNA levels. Results: Robust elevation of m(6)A RNA levels of peripheral blood cells was exhibited in the NSCLC group. Moreover, the m(6)A levels increased as NSCLC progressed, and reduced after treatment. The m(6)A 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 m(6)A levels elevated the AUC to 0.970. Further analysis established that the expression of m(6)A erasers FTO and ALKBH5 were both markedly reduced and negatively correlated with m(6)A 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 m(6)A RNA of peripheral blood immune cells was a prospective biomarker for the diagnosis of NSCLC.

• 单位
  y; 中山大学; 1; 广州医学院