Expression of Aberrant MicroRNAs and p16INK4a Associated with HPV (6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 52, 53, and 56) in Oral Dysplasia and Squamous Cell Carcinoma: A Retrospective Study.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-01-01 DOI:10.5146/tjpath.2024.12909

Layla Hafed, Olfat Shaker, Ghada Ayeldeen, Hatem Amer, Gamilah Al-Qadhi

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Abstract

Objective: A few studies indicate that human papillomavirus (HPV) induces aberrant expression of microRNAs (miRNAs) and correlate this with p16INK4a in oral dysplasia (OD) and oral squamous cell carcinoma (OSCC). Therefore, this study aimed to evaluate the expression of miRNA-21, miRNA-22, and miRNA-224 by q-PCR and the p16 INK4a by immunohistochemical (IHC) as markers for HPV-positive OSCC and OD in comparison to controls as miRNA expression can be altered by the HPV oncogenes and hence can be used as a biomarker for HPV positive cases.

Material and methods: Fifty-two specimens were collected from archived paraffin blocks for patients aged between 19 and 88 (31 males and 21 females) from various oral sites. They were examined by IHC using p16 INK4a , by RT-PCR for the detection of HPV (6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 52, 53, 56), and by q-PCR for the expression of miRNA-21, miRNA-22, and miRNA-224 in positive specimens.

Results: Out of the 15 OD, three were positive by both techniques. Meanwhile, 17 out of all OSCC specimens showed intense nuclear and cytoplasmic staining by p16 INK4a , and only 16 were also positive by RT-PCR. However, all control specimens were negative. MiRNA-21, miRNA-22, and miRNA-224 were overexpressed in 3 specimens of OD and 16 of OSCC.

Conclusion: MiRNA-21, miRNA-22, and miRNA-224, besides p16 INK4a , could be used as indicators for HPV-associated OD and OSCC as their expression is attributed to the HPV oncoprotein. Further studies using follow-up data should be done to correlate it with miRNA overexpression.

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口腔发育不良和鳞状细胞癌中与 HPV（6、11、16、18、31、33、35、42、43、44、45、52、53 和 56）相关的异常 MicroRNA 和 p16INK4a 的表达：一项回顾性研究。

目的：一些研究表明，人类乳头瘤病毒（HPV）会诱导微小RNA（miRNA）的异常表达，并与口腔发育不良（OD）和口腔鳞状细胞癌（OSCC）中的p16INK4a相关。因此，本研究旨在通过q-PCR方法评估miRNA-21、miRNA-22和miRNA-224的表达，并通过免疫组化（IHC）方法评估p16INK4a作为HPV阳性OSCC和OD的标记物与对照组的比较，因为miRNA的表达可被HPV致癌基因改变，因此可用作HPV阳性病例的生物标记物：从归档石蜡块中收集了52份标本，患者年龄在19至88岁之间，来自不同的口腔部位（男性31人，女性21人）。采用 p16 INK4a 进行 IHC 检测，RT-PCR 检测 HPV（6、11、16、18、31、33、35、42、43、44、45、52、53、56），q-PCR 检测阳性标本中 miRNA-21、miRNA-22 和 miRNA-224 的表达：结果：在 15 例阳性病例中，有 3 例同时采用两种技术检测结果均为阳性。同时，在所有 OSCC 标本中，有 17 个标本的 p16 INK4a 细胞核和细胞质染色均呈阳性，只有 16 个标本的 RT-PCR 检测结果也呈阳性。然而，所有对照标本均为阴性。3例OD标本和16例OSCC标本中，miRNA-21、miRNA-22和miRNA-224均出现过表达：结论：除 p16 INK4a 外，miRNA-21、miRNA-22 和 miRNA-224 可作为 HPV 相关 OD 和 OSCC 的指标，因为它们的表达与 HPV 肿瘤蛋白有关。应利用随访数据开展进一步研究，将其与 miRNA 过度表达联系起来。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.