Udompatanakorn Chatchaphan, Taebunpakul Patrayu
Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, Srinakharinwirot University, Bangkok, Thailand.
Eur J Dent. 2023 May;17(2):349-356. doi: 10.1055/s-0042-1747950. Epub 2022 Jul 4.
N6-methyladenosine is the most frequent mRNA modification in eukaryotic cells. It is catalyzed by the methyltransferase complex, methyltransferase-like 3 (METTL3). Previous studies have revealed that METTL3 plays a role in various cancers. However, there is limited information about the roles of METTL3 in oral epithelial dysplasia (OED). This study determined METTL3 expression in normal oral mucosa (NOM), OED, and oral squamous cell carcinoma (OSCC) by immunohistochemistry.
Twenty formalin-fixed paraffin embedded specimens each of NOM, OED, and OSCC were included. The expression pattern, the number of positive cells, the staining intensity, and the histochemical score (H-score) of METTL3 were investigated.
The data were analyzed by using one-way analysis of variance, chi-squared test, and a Kruskal-Wallis test. A value < 0.05 indicated statistically significant.
The METTL3 expression in NOM was observed in the basal, parabasal, and lower layers of epithelium. In low-grade OED, METTL3 was expressed in the lower epithelial layers and partially presented in the spinous layer. However, in high-grade OED, METTL3 expression was observed in the lower layers, spinous layers, and upper layers of dysplastic epithelium. For OSCC, METTL3 immunostaining was presented in both the peripheral and central cells of the tumor islands. All NOM samples showed weak-to-moderate METTL3 staining intensity, while the moderate-to-strong METTL3 staining intensity was observed in 95% of both OED and OSCC specimens ( < 0.05). The percentage of METTL3 positive cells and H-score was highest in OSCC, followed by OED and NOM, respectively ( < 0.05). Interestingly, H-score was greater in high-grade OED (209.8 ± 18.61) when compared with low-grade OED (162.1 ± 38.93) ( < 0.05).
METTL3 expression in OED and OSCC was more outstanding than in NOM, suggesting possible roles for OED and OSCC pathogenesis. Additionally, METTL3 expression may be an indicator for OED progression to OSCC.
N6-甲基腺苷是真核细胞中最常见的mRNA修饰。它由甲基转移酶复合物,即甲基转移酶样3(METTL3)催化。先前的研究表明METTL3在多种癌症中发挥作用。然而,关于METTL3在口腔上皮发育异常(OED)中的作用的信息有限。本研究通过免疫组织化学测定了METTL3在正常口腔黏膜(NOM)、OED和口腔鳞状细胞癌(OSCC)中的表达。
纳入NOM、OED和OSCC的福尔马林固定石蜡包埋标本各20例。研究了METTL3的表达模式、阳性细胞数量、染色强度和组织化学评分(H评分)。
采用单因素方差分析、卡方检验和Kruskal-Wallis检验对数据进行分析。P < 0.05表示差异有统计学意义。
在NOM中,METTL3表达见于上皮的基底、副基底和下层。在低级别OED中,METTL3表达于上皮下层,并部分见于棘层。然而,在高级别OED中,在发育异常上皮的下层、棘层和上层均观察到METTL3表达。对于OSCC,METTL3免疫染色见于肿瘤岛的外周和中央细胞。所有NOM样本均显示METTL3染色强度为弱阳性至中度,而在95%的OED和OSCC标本中观察到中度至强阳性的METTL3染色强度(P < 0.05)。METTL3阳性细胞百分比和H评分在OSCC中最高,其次分别为OED和NOM(P < 0.05)。有趣的是,与低级别OED(162.1±38.93)相比,高级别OED的H评分更高(209.8±18.61)(P < 0.05)。
METTL3在OED和OSCC中的表达比在NOM中更突出,提示其在OED和OSCC发病机制中可能发挥作用。此外,METTL3表达可能是OED进展为OSCC的一个指标。