Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran.
J Med Virol. 2024 Mar;96(3):e29501. doi: 10.1002/jmv.29501.
While infection with high-risk human papillomavirus (HPV) types is necessary for cervical cancer (CC) development, it is not enough, and other risk factors are required. Several studies have reported the activation of HERV-K in different cancers; however, the investigation of HERV-K expression levels in CC is scarce. In this study, it was hypothesized that activation of HERV-K could play an essential role in CC development. In this order, the expression levels of HERV-K Env, Np9, and Rec transcripts were investigated on 147 normal to CC uterine cervical tissues using quantitative real-time PCR. The significantly higher levels of HERV-K Env and Np9 transcripts were found in patients with cervical intraepithelial neoplasia (CIN) II-III and CC groups compared to those in the normal/CIN I group. Expression of Rec transcript was also higher only in the CC group than normal/CIN I group. Among CC patients, meaningfully higher levels of HERV-K Env and Np9 transcripts were found in patients with squamous cell carcinoma rather than in adenocarcinoma. When only the HPV 16 positive samples were investigated, it was found that the mean difference in Env and Np9 mRNA levels was meaningfully higher among precancer lesions and the cancer group in comparison with the normal group. However, the Rec mRNA level showed no significant differences. The association between the expression of HERV-K genes was investigated, and a significant positive correlation of Env expression with Np9 transcript was found only in the group with precancer lesions (R = 0.6, p = 0.0037). Moreover, a significant positive correlation was found between Rec and Np9 transcripts in patients with normal cervix tissues (R = 0.26, p = 0.033). However, no correlations were observed between the expression of Env and Rec in the three groups. In conclusion, our results showed that HERV-K transcripts, especially Env and Np9, upregulated during cervical lesion progression. These findings highlight the potential use of HERV-K Env and Np9 as biomarkers for CC diagnosis and prognosis. Further investigation is needed to determine the clinical utility of these markers and whether targeting HERV-K oncogenes could be a viable therapeutic strategy for CC.
虽然高危型人乳头瘤病毒(HPV)感染是宫颈癌(CC)发展的必要条件,但这还不够,还需要其他危险因素。几项研究报告了 HERV-K 在不同癌症中的激活;然而,CC 中 HERV-K 表达水平的研究很少。在这项研究中,假设 HERV-K 的激活可能在 CC 发展中发挥重要作用。为此,使用定量实时 PCR 研究了 147 例正常至 CC 子宫颈组织中 HERV-K Env、Np9 和 Rec 转录本的表达水平。与正常/CIN I 组相比,CIN II-III 和 CC 组患者的 HERV-K Env 和 Np9 转录本水平显著升高。Rec 转录本的表达也仅在 CC 组中高于正常/CIN I 组。在 CC 患者中,与腺癌相比,鳞状细胞癌患者的 HERV-K Env 和 Np9 转录本水平显著升高。当仅研究 HPV 16 阳性样本时,发现与正常组相比,癌前病变和癌症组的 Env 和 Np9 mRNA 水平的平均差异具有统计学意义。然而,Rec mRNA 水平没有显著差异。还研究了 HERV-K 基因表达之间的相关性,仅在癌前病变组中发现 Env 表达与 Np9 转录本之间存在显著正相关(R=0.6,p=0.0037)。此外,在正常宫颈组织的患者中发现 Rec 和 Np9 转录本之间存在显著正相关(R=0.26,p=0.033)。然而,在三组中均未观察到 Env 和 Rec 表达之间的相关性。总之,我们的研究结果表明,HERV-K 转录本,特别是 Env 和 Np9,在宫颈病变进展过程中上调。这些发现强调了 HERV-K Env 和 Np9 作为 CC 诊断和预后标志物的潜在用途。需要进一步研究以确定这些标志物的临床实用性以及针对 HERV-K 癌基因是否可能成为 CC 的可行治疗策略。