Correlation between METTL3 overexpression and ¹⁸F-FDG uptake in patients with soft tissue sarcoma

Background: N6-methyladenosine (m6A) methylation plays a key role in tumor progression. However, the significance of methyltransferase-like 3 (METTL3) in biological processes of soft tissue sarcoma (STS) patients, and the relationship between METTL3 and STS are unclear.

Methods: The expression of METTL3 in STS and its relationship with patient prognosis were determined from database analyses. Immunohistochemical staining and ¹⁸F-FDG radioautography were performed on tumor tissues from 39 patients with STS undergoing ¹⁸F-FDG PET before treatment. METTL3 expression in tumor and peritumoral tissues was evaluated with the Wilcoxon test. The Mann-Whitney U test and Spearman's correlation analysis were used to explore correlations of METTL3 expression with both clinicopathological characteristics and ¹⁸F-FDG uptake. One-way analysis of variance and ROC analysis were used to evaluate the efficacy of ¹⁸F-FDG PET metabolic parameters in predicting METTL3 expression.

Results: METTL3 expression was significantly higher in STS tumor tissues than normal tissues (all p values<0.01), and correlated with poor patient prognosis (p < 0.05). METTL3 expression was associated with histological differentiation (Z=-2.026, p = 0.043), but no significant difference was observed according to age, sex, tumor size, tumor location, or metastasis (all p values > 0.05). METTL3 expression positively correlated with the expression of CD163 (r = 0.502, p = 0.011), CD68 (r = 0.381, p = 0.017), and CD8 (r = 0.319, p = 0.048), and exhibited a trend toward correlation with CD4 expression (r = 0.310, p = 0.055). Moreover, ¹⁸F-FDG metabolism positively correlated with METTL3 expression in STS (r = 0.580 for PET and r = 0.434 for radioautography, all p values<0.01). The SUVmax of PET was significantly higher in tumors with high rather than low METTL3 expression (Z=-2.979, p = 0.003).

Conclusions: METTL3 was overexpressed in STS, which may be a meaningful target of action in STS patients. The ¹⁸F-FDG uptake was significantly elevated in tumors with high METTL3 expression, SUVmax could provide a meaningful imaging biomarker for its expression.