Resolution of oncogene-induced senescence markers in HPV-infected cervical cancer tissue.

IF 3.4 2区医学 Q2 ONCOLOGY

BMC Cancer Pub Date : 2025-01-21 DOI:10.1186/s12885-025-13499-0

Ashraf I Khasawneh, Sofian Al Shboul, Nisreen Himsawi, Amani Al Rousan, Nisreen Abu Shahin, Mohammed El-Sadoni, Ahmad Alhesa, Ala' Abu Ghalioun, Suzan Khawaldeh, Bayan Shawish, Salem Abu Mahfouz, Mais Al-Shayeb, Shatha Abo Dawoud, Raghad Tlilan, Mohammad Nuseir, Moureq R Alotaibi, Ola Abu Al Karsaneh, Fida Asali, Marcos Yébenes Mayordomo, Raghda Barham, Rame Khasawneh, Tareq Saleh

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引用次数: 0

Abstract

Background: Oncogene-Induced Senescence (OIS) is a form of senescence that occurs as a consequence of oncogenic overstimulation and possibly infection by oncogenic viruses. Whether senescence plays a role in the pathogenesis of cervical cancer (CC) is not well understood. Moreover, whether cervical epithelial cells that are part of the premalignant cervical intraepithelial neoplasia (CIN), exhibit markers of OIS in Human Papillomavirus (HPV)-infected tissue, has not been investigated.

Methods: We utilized a set of patient-derived premalignant and malignant tissue samples to investigate the protein (Ki67 and Lamin B1) and gene (TP53, IL1A, CCL2, and MMP9) expression of several OIS-associated biomarkers using immunohistochemistry (IHC) and qRT-PCR, respectively. Furthermore, we characterized the HPV status of all tissue samples.

Results: Most of the CC samples (34/37) were positive for HPV, mainly HPV-16 which was observed in 62.2% of the CC samples. Among CINs, HPV infection was found in 60.2% of the 32 samples with HPV-16 as the dominant genotype in 58.5% of the CINs. IHC analysis revealed a significant increase in the expression levels of both Ki67 and Lamin B1 proteins in CC tissue compared to CIN. On average, 93% of tumor cells were positive for Ki67 in comparison to only 25% of premalignant cells in CIN samples. Similarly, Lamin B1 expression was observed in 89% of tumor cells in malignant tissue on average, compared to 60% in CIN samples. Importantly, Lamin B1 expression was elevated in nonmalignant cervical tissue suggesting that its downregulation is more predominant in the premalignant state. Furthermore, RT-PCR revealed a significant decrease in the expression of TP53, IL1a, CCL2, and MMP9 markers in CC samples compared to CINs. Specifically, 84% of CC samples showed reduced TP53 expression, 90% showed reduced IL1a expression, 74% showed reduced CCL2 expression, and 76% showed reduced MMP9 expression when compared with their premalignant baseline. Infection of HPV was confirmed in 61% of the tumor tissues while only 25% of the CINs were positive for HPV.

Conclusion: This work shall provide an opportunity to further examine the role of OIS in the process of HPV-driven CC development.

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hpv感染宫颈癌组织中癌基因诱导的衰老标志物的测定。

背景：癌基因诱导的衰老（OIS）是一种由于致癌过度刺激和可能被致癌病毒感染而发生的衰老形式。衰老是否在宫颈癌（CC）的发病机制中起作用尚不清楚。此外，作为宫颈癌前上皮内瘤变（CIN）一部分的宫颈上皮细胞，是否在人乳头瘤病毒（HPV）感染的组织中表现出OIS标志物，尚未被研究。方法：采用免疫组化（IHC）技术和qRT-PCR技术，分别利用患者来源的癌前和恶性组织样本，研究了几种ois相关生物标志物的蛋白（Ki67和Lamin B1）和基因（TP53、IL1A、CCL2和MMP9）表达情况。此外，我们表征了所有组织样本的HPV状态。结果：绝大多数CC标本（34/37）HPV阳性，其中以HPV-16阳性为主，阳性率为62.2%。在32份CINs中，60.2%的样本中发现HPV感染，58.5%的CINs中HPV-16为优势基因型。免疫组化分析显示，与CIN相比，CC组织中Ki67和Lamin B1蛋白的表达水平显著增加。平均而言，93%的肿瘤细胞Ki67呈阳性，而CIN样本中只有25%的癌前细胞呈阳性。同样，在恶性组织中，平均89%的肿瘤细胞中观察到Lamin B1的表达，而在CIN样本中，这一比例为60%。重要的是，Lamin B1在非恶性宫颈组织中表达升高，表明其下调在癌前状态更为明显。此外，RT-PCR显示，与CINs相比，CC样本中TP53、IL1a、CCL2和MMP9标志物的表达显著降低。具体来说，与癌前基线相比，84%的CC样本显示TP53表达降低，90%的CC样本显示IL1a表达降低，74%的CC样本显示CCL2表达降低，76%的CC样本显示MMP9表达降低。61%的肿瘤组织证实有HPV感染，而只有25%的CINs呈HPV阳性。结论：本研究为进一步研究OIS在hpv驱动CC发展过程中的作用提供了机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Cancer 医学-肿瘤学

CiteScore

6.00

自引率

2.60%

发文量

1204

审稿时长

6.8 months

期刊介绍： BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.