Novel blood-based FUT7 DNA methylation is associated with lung cancer: especially for lung squamous cell carcinoma

Abstract

Background The death rate of lung cancer (LC) ranks first in the world. Changes of DNA methylation in peripheral blood may be related to malignant tumors. It is necessary to explore blood-based biomarkers of methylation to detect LC. Methods Mass spectrometry assays were conducted to measure DNA methylation levels of seven CpG sites within FUT7 gene in the peripheral blood of 428 patients with LC, 233 patients with benign pulmonary nodule (BPN) and 862 normal controls (NC). The odds ratios (ORs) of all CpG sites were evaluated for their risk to LC using per SD change and tertiles analyses by logistic regression. The predictive ability of the seven FUT7 CpG sites and risk factors were evaluated by receiver operating characteristic curve (ROC). Results The methylation levels of seven CpG sites of FUT7 in LC were significantly lower than that in NC (P < 0.05). The per SD decrement of methylation level in CpG_1-7 was significantly associated with 65%, 38%, 59%, 46%, 23%, 20% and 68% higher risk for LC versus NC, respectively, and the adjusted ORs (95% CI) were 2.92 (2.17–3.96), 1.76 (1.29–2.38), 2.83 (2.09–3.82), 3.00 (2.17–4.16), 1.81 (1.35–2.43), 1.48 (1.11–1.97) and 3.04 (2.23–4.16) for the lowest tertiles of methylation level in CpG_1-7 compared with the top tertiles, respectively. The area under the curve (AUC) of FUT7_CpG_1-7 was 0.659 (CI 0.626–0.693), 0.792 (CI 0.736–0.848) and 0.729 (CI 0.665–0.792) in distinguishing LC versus NC, LUSC versus NC and LUSC versus BPN. Conclusions Our study revealed an association between FUT7 hypomethylation and LC, especially for LUSC, which provides novel support for the blood-based methylation signatures as potential marker for assessing lung cancer risk.

FAM20A: a potential diagnostic biomarker for lung squamous cell carcinoma

“…This study analyzed the relationship between CTLA-4 and FAM20A and found a positive correlation in their expression in LUSC. CTLA-4 interacts with CD80, thereby limiting T-cell activation and leading to immune dysfunction (41). Interestingly, the level of CD80 and FAM20A was also favorably correlated.…”

“…Methylation of CpG sites in the promoter region is believed to influence the process of DNA transcription by silencing the transcription factors ( 43 ), and without altering the DNA sequence. The methylation of AKAP13, nuclear receptor binding SET domain protein 3 (NSD3), and FUT7 are connected with the diagnosis of LUSC patients ( 44 , 45 ). Our study indicated that hypermethylation of cg24064639 is associated with poorer prognosis, suggesting that epigenetic changes might impact LUSC progression by inhibiting FAM20A transcription.…”

Targeting protein glycosylation to regulate inflammation in the respiratory tract: novel diagnostic and therapeutic candidates for chronic respiratory diseases

“…FUT4 and FUT7 may also participate in lung-to-brain metastasis of NSCLC cells ( 117 ). Reduced levels of FUT7 CpG DNA methylation have been found in lung cancer, especially in LUSC ( 118 ), and FUT7 promotes lung cancer proliferation by activation of the EGFR/AKT/mTOR signal pathway ( 119 ). FUT8, whose expression is upregulated in most cancers, regulates the core fucosylation of PD-1 ( 120 , 121 ), PD-L2 ( 122 ), TGF-β ( 123 ), TNFR ( 124 ), EGFR ( 78 , 125 , 126 ), B7H3 ( 127 ), α3β1 integrin ( 128 ), and E-cadherin ( 129 ) as well as that of mucins ( 130 ).…”

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“…This study analyzed the relationship between CTLA-4 and FAM20A and found a positive correlation in their expression in LUSC. CTLA-4 interacts with CD80, thereby limiting T-cell activation and leading to immune dysfunction (41). Interestingly, the level of CD80 and FAM20A was also favorably correlated.…”