J Cancer 2020; 11(16):4851-4860. doi:10.7150/jca.44754 This issue

Research Paper

Overexpression of METTL3 associated with the metabolic status on 18F-FDG PET/CT in patients with Esophageal Carcinoma

Xu-Sheng Liu1, Ling-Ling Yuan2, Yan Gao1, Lu-Meng Zhou1, Jian-Wei Yang1, Zhi-Jun Pei1,3,4✉

1. Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 44200, China.
2. Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China.
3. Hubei Key Laboratory of WudangLocal Chinese Medicine Research, Shiyan, 442000, China.
4. Hubei Key Laboratory of Embryonic Stem Cell Research, Shiyan, 442000, China.

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Liu XS, Yuan LL, Gao Y, Zhou LM, Yang JW, Pei ZJ. Overexpression of METTL3 associated with the metabolic status on 18F-FDG PET/CT in patients with Esophageal Carcinoma. J Cancer 2020; 11(16):4851-4860. doi:10.7150/jca.44754. Available from https://www.jcancer.org/v11p4851.htm

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Background: To investigate the expression of methyltransferase 3 (METTL3) and its relationship with 18F-FDG uptake in patients with esophageal carcinoma (ESCA).

Materials and methods: This study analyzed the expression of METTL3 in ESCA and its relationship with clinicopathological features by The Cancer Genome Atlas (TCGA) database. Immunohistochemical staining was performed on 57 tumor tissues of ESCA patients who underwent PET/CT scan before surgery to evaluate the expression of METTL3, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in tumor tissues and peritumoral tissues. Analyze the relationship between SUVmax with METTL3, HK2, and GLUT1 expression.

Results: The expression of METTL3, GLUT1, and HK2 was significantly increased in ESCA tissues compared with normal tissues (p < 0.001). The expression of METTL3 was correlated with tumor size and histological differentiation (p < 0.05), and there was no significant difference between age, sex, pathological types, tumor staging, or lymph node metastasis (p > 0.05). The SUVmax was significantly higher in tumors with high METTL3 expression (17.822±6.249) compared to low METTL3 expression (9.573±5.082) (p < 0.001). There was a positive correlation between the SUVmax and METTL3 expression in ESCA (r2 = 0.647, p < 0.001). Multivariate analysis confirmed the association between SUVmax and METTL3 expression (p < 0.05). GLUT1 and HK2 expression in ESCA was positively correlated with 18F-FDG uptake and METTL3 status (p < 0.001).

Conclusions: The high expression of METTL3 is related to the high SUVmax in ESCA, and METTL3 may increase 18F-FDG uptake by regulating GLUT1 and HK2.

Keywords: Esophageal carcinoma, methyltransferase 3, 18F-FDG, glucose transporter 1, hexokinase 2