Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, 80131 Naples, Italy.
Pathology Unit, Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy.
Int J Mol Sci. 2023 Jun 27;24(13):10729. doi: 10.3390/ijms241310729.
Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women.
Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression.
We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ = 4.227; = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ = 0.676; = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027-20.347; = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084-42.476; = 0.041).
In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes.
神经营养因子，如 BDNF 和 NGF，在宫颈癌肿瘤细胞中过度表达，而 HIV 感染与神经营养因子表达的上调有关。因此，我们旨在研究 HIV 感染妇女的宫颈癌前病变中是否存在 BDNF 和 NGF 的过度表达。
前瞻性纳入患有宫颈癌前病变（宫颈上皮内瘤变 2 级或 3 级）的妇女，并根据其 HIV 状况进行分组。对疑似宫颈癌的环形电切术（LEEP）标本进行免疫组化分析，以评估 BDNF 和 NGF 的表达。
我们对 12 名 HIV 感染患者进行了分析，并与 23 名 HIV 阴性患者作为对照组进行了匹配。免疫组化分析显示，与对照组相比，HIV 阳性妇女的宫颈前病变中 BDNF 表达显著升高。特别是，BDNF 在 8/12 名 HIV 阳性患者和 7/23 名 HIV 阴性患者中表达（66.7%比 30.4%，χ=4.227；=0.040）。与对照组相比，HIV 阳性妇女的宫颈前病变中 NGF 表达并无显著升高。特别是，NGF 在 8/12 名 HIV 阳性患者和 12/23 名 HIV 阴性患者中表达（66.7%比 52.2%，χ=0.676；=0.411）。Logistic 回归分析显示，当单独考虑时（粗 OR 4.6，95%CI 0.027-20.347；=0.046）和与其他协变量一起分析时（调整 OR 6.786，95%CI 1.084-42.476；=0.041），HIV 状态是前病变性宫颈癌前疾病中 BDNF 表达的独立预测因子。
在宫颈癌前病变中，与非感染对照相比，HIV 感染妇女的 BDNF 表达更高，这与患者的临床特征以及 HPV-HR 基因型无关。BDNF 可以作为 HIV 和 HPV 相互作用加速宫颈癌进展和侵袭的途径之间的联系发挥关键作用。这些数据可以帮助更好地了解神经营养因子在宫颈癌发生中的作用以及改善疾病结局的可能治疗策略。
