Ukey Shweta, Jain Ankit, Dwivedi Shailendra, Choudhury Chinmayee, Vishnoi Jeewan Ram, Chugh Ankita, Purohit Purvi, Pareek Puneet, Elhence Poonam, Misra Sanjeev, Sharma Praveen
All India Institute of Medical Sciences, Jodhpur, Rajasthan 342005 India.
All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh India.
Indian J Clin Biochem. 2023 Jan;38(1):73-82. doi: 10.1007/s12291-022-01035-x. Epub 2022 Apr 29.
Oral squamous cell carcinoma (OSCC) is one of the common types of cancer. Its progression follows a transition from oral potentially malignant disorders (OPMDs) such as oral submucous fibrosis (OSMF). Epigenetic modifiers, especially microRNAs (miRNAs), have an appreciable role in the regulation of various carcinogenic pathways which are being used as biomarkers. miRNAs may also be helpful in the differentiation of oral submucous fibrosis from oral squamous cell carcinoma. Three miRNAs, miR-221-3p, miR133a-3p, and miR-9-5p, were found differentially expressed in many cancers in the literature search supported by our preliminary database search-based screening. The literature and our functional enrichment analysis in an earlier study have reported these miRNAs to regulate carcinogenesis at various steps. In the present study, the expression of these miRNAs was examined in 34 histopathologically confirmed OSCC, 30 OSMF, and 29 control (healthy volunteers) human samples. There was a significant downregulation of miRNA-133a-3p in OSCC compared to OSMF and controls, whereas there was up-regulation in oral submucous fibrosis compared to controls. There was no significant difference in the expression of miR-221-3p between OSCC and OSMF, but an upregulation in OSCC compared to controls. miR-9-5p was also found upregulated in both OSCC and OSMF. Further, miR-133a-3p expression was negatively correlated with age, smoking, drinking status, and AJCC staging, whereas miR-9-5p expression was only positively associated with tobacco/ areca nut chewing. The ROC plots, logistic regression model generated, and the correlation between the expression of miR-9-5p and miR-133a-3p in blood and tissue suggests that these could be used as risk stratification biomarkers.
口腔鳞状细胞癌（OSCC）是常见的癌症类型之一。其发展过程是从口腔潜在恶性疾病（OPMDs）如口腔黏膜下纤维化（OSMF）转变而来。表观遗传修饰因子，尤其是微小RNA（miRNAs），在调控各种致癌途径中发挥着重要作用，这些途径正被用作生物标志物。miRNAs在区分口腔黏膜下纤维化和口腔鳞状细胞癌方面也可能有所帮助。在我们基于初步数据库搜索的筛选支持下的文献检索中发现，三种miRNAs，即miR-221-3p、miR133a-3p和miR-9-5p，在许多癌症中差异表达。文献以及我们早期研究中的功能富集分析表明，这些miRNAs在致癌过程的各个步骤中发挥调控作用。在本研究中，检测了34例经组织病理学确诊的OSCC、30例OSMF和29例对照（健康志愿者）人体样本中这些miRNAs的表达。与OSMF和对照相比，OSCC中miRNA-133a-3p显著下调，而与对照相比，口腔黏膜下纤维化中miRNA-133a-3p上调。OSCC和OSMF之间miR-221-3p的表达无显著差异，但与对照相比，OSCC中miR-221-3p上调。miR-9-5p在OSCC和OSMF中均上调。此外，miR-133a-3p的表达与年龄、吸烟、饮酒状况和美国癌症联合委员会（AJCC）分期呈负相关，而miR-9-5p的表达仅与烟草/槟榔咀嚼呈正相关。ROC曲线、生成的逻辑回归模型以及血液和组织中miR-9-5p和miR-133a-3p表达之间的相关性表明，这些可作为风险分层生物标志物。
