Shima Kaori, Shimojukkoku Yudai, Oku Yasunobu, Higashimoto Kanako, Tsuchiyama Takahiro, Kajiya Yuka, Kurihara-Shimomura Miyako, Sasahira Tomonori
Department of Molecular Oral Pathology and Oncology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Department of Oral Surgery, Saitama Cancer Center, Saitama, Japan.
Diagn Pathol. 2025 Jul 3;20(1):81. doi: 10.1186/s13000-025-01678-3.
Oral squamous cell carcinoma (OSCC) is associated with poor prognosis due to extensive local invasiveness and lymph node metastasis, often leading to a significant decrease in aesthetics and function after surgery. Therefore, elucidation of the molecular mechanisms underlying OSCC is necessary for its early detection and treatment. N6-methyladenosine (m6A) modification of mRNA is the most common form of post-transcriptional RNA methylation and is often involved in the progression of cancer by regulating the expression of various genes. Recent studies reported the tumor-promoting effects of vir-like m6A methyltransferase associated (VIRMA, also termed KIAA1429), a novel molecule involved in m6A modification; however, its role in OSCC remains poorly understood.
In the present study, we determined the total m6A levels and VIRMA expression in OSCC using immunohistochemistry of tissue specimens and evaluated their association with clinicopathologic characteristics. We also performed gene expression analysis of VIRMA/KIAA1429 using public datasets.
We found that the m6A levels were significantly higher in the OSCC specimens of patients with a more advanced clinical stage (P = 0.0063), lymph node metastasis (P = 0.0323), and venous invasion (P = 0.0380) compared to those without. The analysis of the public datasets revealed that VIRMA/KIAA1429 expression levels were higher in head and neck SCC than in normal mucosa, whereas immunohistochemistry revealed that VIRMA-expressing OSCC was associated with a significantly shorter disease-free survival (P = 0.0043) and was an independent poor prognostic factor (P = 0.0179).
These results highlight the potential utility of RNA methylation and VIRMA expression for the diagnosis and treatment of OSCC.
口腔鳞状细胞癌（OSCC）因具有广泛的局部侵袭性和淋巴结转移，预后较差，常导致术后美观和功能显著下降。因此，阐明OSCC潜在的分子机制对于其早期检测和治疗至关重要。mRNA的N6-甲基腺苷（m6A）修饰是转录后RNA甲基化最常见的形式，常通过调节各种基因的表达参与癌症进展。最近的研究报道了病毒样m6A甲基转移酶相关蛋白（VIRMA，也称为KIAA1429）的促肿瘤作用，VIRMA是一种参与m6A修饰的新分子；然而，其在OSCC中的作用仍知之甚少。
在本研究中，我们通过组织标本的免疫组织化学检测确定了OSCC中的总m6A水平和VIRMA表达，并评估了它们与临床病理特征的相关性。我们还使用公共数据集对VIRMA/KIAA1429进行了基因表达分析。
我们发现，与无上述情况的患者相比，临床分期较晚（P = 0.0063）、有淋巴结转移（P = 0.0323）和有静脉侵犯（P = 0.0380）的患者的OSCC标本中m6A水平显著更高。对公共数据集的分析显示，头颈部鳞状细胞癌中VIRMA/KIAA1429的表达水平高于正常黏膜，而免疫组织化学显示，表达VIRMA的OSCC与无病生存期显著缩短相关（P = 0.0043），并且是一个独立的不良预后因素（P = 0.0179）。
这些结果突出了RNA甲基化和VIRMA表达在OSCC诊断和治疗中的潜在应用价值。
