异常微 RNA 和 HPV（6、11、16、18、31、33、35、42、43、44、45、52、53 和 56）相关的 p16INK4a 在口腔发育异常和鳞状细胞癌中的表达：一项回顾性研究。
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.
机构信息
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, CAIRO, EGYPT.
Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Cairo University, CAIRO, EGYPT.
出版信息
Turk Patoloji Derg. 2024;40(3):149-161. doi: 10.5146/tjpath.2024.12909.
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 < sup > INK4a < /sup > 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 < sup > INK4a < /sup > , 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 < sup > INK4a < /sup > , 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 < sup > INK4a < /sup > , 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.
目的
一些研究表明，人乳头瘤病毒（HPV）会导致微小 RNA（miRNA）的异常表达，并与口腔上皮内瘤变（OD）和口腔鳞状细胞癌（OSCC）中的 p16INK4a 相关。因此，本研究旨在通过 qPCR 评估 miRNA-21、miRNA-22 和 miRNA-224 的表达，并通过免疫组织化学（IHC）评估 p16INK4a 作为 HPV 阳性 OSCC 和 OD 的标志物，与对照组进行比较，因为 miRNA 的表达可能会受到 HPV 致癌基因的影响，因此可以作为 HPV 阳性病例的生物标志物。
材料和方法
从不同口腔部位的 52 名年龄在 19 至 88 岁之间的患者的存档石蜡块中收集标本（31 名男性和 21 名女性）。使用 p16INK4a 通过 IHC 对其进行检查，使用 RT-PCR 检测 HPV（6、11、16、18、31、33、35、42、43、44、45、52、53、56），并使用 qPCR 检测阳性标本中 miRNA-21、miRNA-22 和 miRNA-224 的表达。
结果
在 15 例 OD 中，有 3 例两种技术均为阳性。同时，所有 OSCC 标本中，有 17 例 p16INK4a 显示强烈的核和细胞质染色，只有 16 例通过 RT-PCR 也是阳性。然而，所有对照标本均为阴性。miRNA-21、miRNA-22 和 miRNA-224 在 3 例 OD 和 16 例 OSCC 中过表达。
结论
miRNA-21、miRNA-22 和 miRNA-224 除了 p16INK4a 之外，还可以作为 HPV 相关 OD 和 OSCC 的标志物，因为它们的表达归因于 HPV 致癌蛋白。应进一步进行使用随访数据的研究，以将其与 miRNA 过表达相关联。
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