Correlation between HPV PCNA, p16, and p21 Expression in Lung Cancer Patients

IF 2.6 2区生物学 Q3 CELL BIOLOGY

Cellular Microbiology Pub Date : 2022-09-28 DOI:10.1155/2022/9144334

B. Marcos, T. H. A. de Oliveira, C. M. D. do Amaral, M. T. Muniz, A. C. Freitas

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引用次数: 1

Abstract

Purpose. Evaluate if human papillomavirus (HPV) infection in lung cancer patients might be helping cancer development by altering p16, p21, and PCNA, key human genes involved in cell proliferation and tumor development. Methods. 63 fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) samples from lung tumor patients were used to detect HPV by PCR, followed by genotype through sequencing. The host gene expressions of p21, p16, and PCNA were quantified by qPCR in both FF and FFPE samples, and the expression of viral oncogenes E5, E6, and E7 was also measured by qPCR in 19 FF samples. Results. 74.6% of samples were positive for HPV, 33/44 FFPE samples and 14/19 FF samples. HPV-16 and HPV-18 were detected in 31/33 and 7/33 FFPE, respectively, and HPV-16 was the only type in FF samples. E5, E6, and E7 were expressed in 10/19, 2/19, and 4/19 FF samples, respectively. The p16 RNAm expression was higher in FF HPV+ samples and FFPE+FF HPV+ samples, while p21 showed higher expression in all HPV- samples. In turn, the PCNA expression was higher in HPV+ FF samples; however, in FFPE and FFPE+FF samples, PCNA was higher in HPV- samples. In FF samples, PCNA, p16, and p21 showed a significant positive correlation as well as E5 and E7, and E5 was inversely correlated to p21. In FFPE, also, a positive correlation was observed between PCNA HPV+ and p21 HPV+ and PCNA HPV+ and p16 HPV. In FF+FFPE analysis, a direct correlation was found between PCNA HPV+ and p21 HPV+, p21 HPV+ and p16 HPV+, and PCNA HPV- and p16 HPV-, and an inverse correlation between PCNA HPV+ and p16 HPV+. Also, the p16 protein was positive in 10 HPV+ samples and 1 HPV-. Conclusions. Our data show that lung cancer patients from Northeast Brazil have a high prevalence of HPV, and the virus also expresses its oncogenes and correlates with key human genes involved in tumor development. This data could instigate the development of studies focused on preventive strategies, such as vaccination, used as a prognostic indicator and/or individualized therapy.

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肺癌患者HPV PCNA、p16和p21表达的相关性

意图评估癌症患者的人乳头瘤病毒（HPV）感染是否可能通过改变p16、p21和PCNA（参与细胞增殖和肿瘤发展的关键人类基因）来帮助癌症的发展。方法。采用63份新鲜冷冻（FF）和福尔马林固定石蜡包埋（FFPE）肺肿瘤患者的样本，通过PCR检测HPV，然后通过测序检测基因型。通过qPCR对FF和FFPE样本中p21、p16和PCNA的宿主基因表达进行定量，并通过qPCR测定19个FF样本中病毒致癌基因E5、E6和E7的表达。后果74.6%的样本为HPV阳性，33/44份FFPE样本和14/19份FF样本。在31/33和7/33的FFPE中分别检测到HPV-16和HPV-18，并且HPV-16是FF样品中唯一的类型。E5、E6和E7分别在10/19、2/19和4/19 FF样品中表达。p16RNAm在FF HPV+样本和FFPE+FF HPV＋样本中表达较高，而p21在所有HPV-样本中表达均较高。反过来，PCNA在HPV+FF样本中的表达更高；然而，在FFPE和FFPE+FF样本中，HPV样本中PCNA较高。在FF样本中，PCNA、p16和p21与E5和E7呈显著正相关，E5与p21呈负相关。在FFPE中，PCNA HPV+和p21 HPV+以及PCNA HPW+和p16 HPV之间也观察到正相关。在FF+FFPE分析中，发现PCNA HPV+与p21 HPV+、p21 HPW+与p16 HPV+以及PCNA HPV-与p16 HPV-之间存在直接相关性，而PCNA HPW+和p16 HPV-之间存在反相关性。此外，p16蛋白在10个HPV+样本和1个HPV-样本中呈阳性。结论。我们的数据显示，来自巴西东北部的癌症患者的HPV患病率很高，该病毒也表达其致癌基因，并与参与肿瘤发展的关键人类基因相关。这些数据可以推动专注于预防策略的研究的发展，如疫苗接种，用作预后指标和/或个体化治疗。

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来源期刊

Cellular Microbiology 生物-微生物学

CiteScore

9.70

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.