Laboratório de Nanobiotecnologia, Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia, Brazil.
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, Brazil.
Histopathology. 2019 Jan;74(2):227-238. doi: 10.1111/his.13713. Epub 2018 Oct 29.
Studies on epigenetics in oral squamous cell carcinoma (OSCC) are rare. Histone modifications comprise epigenetic mechanisms that perform a key role in gene transcription and may regulate tumour development. Thus, the aim of this study was to determine whether two post-translational histone modifications, i.e. phosphorylation of serine 10 in histone H3 and acetylation of lysine 12 in histone H4, have prognostic value for OSCC patients.
Paraffin-embedded tissue samples of 90 patients diagnosed with OSCC were obtained and subjected to immunohistochemical staining with antibodies against histone H3 with phosphorylation of serine 10 (H3S10ph) and histone H4 with acetylation of lysine 12 (H4K12ac). The associations of H3S10ph and H4K12ac expression levels with clinicopathological factors were determined. Five-year survival analysis and univariate and multivariate analyses were also performed. Both H3S10ph and H4K12ac were expressed in the nuclei of tumour cells. A low median of H3S10ph expression was significantly associated with cervical lymph node metastasis. Tumours with high H4K12ac expression were significantly associated with gender, alcohol consumption, and cervical lymph node metastasis. H4K12ac was also shown to have independent prognostic value in the multivariate analysis. Tumours with high H3S10ph expression, size >40 mm, an advanced stage and the presence of cervical lymph node metastases were associated with a better 5-year survival rate. Tumours with low H4K12ac expression, size >40 mm, an advanced stage and cervical lymph node metastasis were associated with a better 5-year survival rate.
These findings suggest that H3S10ph, and mainly H4K12ac, may play a role in OSCC progression and the occurrence of cervical lymph node metastasis. Also, the expression level of H4K12ac could be an independent prognostic factor for OSCC patients.
口腔鳞状细胞癌（OSCC）的表观遗传学研究较少。组蛋白修饰包括在基因转录中起关键作用的表观遗传机制，并可能调节肿瘤的发展。因此，本研究旨在确定两种翻译后组蛋白修饰，即组蛋白 H3 丝氨酸 10 的磷酸化（H3S10ph）和组蛋白 H4 赖氨酸 12 的乙酰化（H4K12ac），是否对 OSCC 患者具有预后价值。
获得了 90 例诊断为 OSCC 的患者的石蜡包埋组织样本，并使用针对组蛋白 H3 丝氨酸 10 磷酸化（H3S10ph）和组蛋白 H4 赖氨酸 12 乙酰化（H4K12ac）的抗体进行免疫组织化学染色。确定 H3S10ph 和 H4K12ac 表达水平与临床病理因素的关联。还进行了 5 年生存分析以及单变量和多变量分析。H3S10ph 和 H4K12ac 在肿瘤细胞的核内表达。H3S10ph 表达中位数较低与颈部淋巴结转移显著相关。H4K12ac 表达较高的肿瘤与性别、饮酒和颈部淋巴结转移显著相关。在多变量分析中，H4K12ac 也具有独立的预后价值。H3S10ph 表达较高、肿瘤大小>40mm、晚期和存在颈部淋巴结转移的肿瘤与 5 年生存率较高相关。H4K12ac 表达较低、肿瘤大小>40mm、晚期和颈部淋巴结转移的肿瘤与 5 年生存率较高相关。
这些发现表明，H3S10ph，主要是 H4K12ac，可能在 OSCC 进展和颈部淋巴结转移的发生中起作用。此外，H4K12ac 的表达水平可能是 OSCC 患者的独立预后因素。
