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ΔNp63 与 TAp63 的表达比值可作为宫颈癌预后的潜在分子标志物。

ΔNp63 to TAp63 expression ratio as a potential molecular marker for cervical cancer prognosis.

机构信息

Department of Biomedical Laboratory Science, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.

Department of Pathology, Yonsei University Wonju College of Medicine, Wonju-si, Gangwon-do, Republic of Korea.

出版信息

PLoS One. 2019 Apr 11;14(4):e0214867. doi: 10.1371/journal.pone.0214867. eCollection 2019.

Abstract

p63 is a transcription factor p53 family. Two major isoforms of p63, TAp63 with transactivation (TA) domain and ΔNp63 with truncated TA domain, have been reported to play opposing roles either in tumor suppression or oncogenic function. Little is known about the association of these two isoforms of p63 in the carcinogenesis of cervical cancer. In this study, the mRNA expression levels of TAp63 and ΔNp63 in 40 normal, 30 low-grade squamous intraepithelial lesions (LSIL), 38 high-grade squamous intraepithelial lesions (HSIL), and 52 cervical cancer formalin-fixed paraffin-embedded tissues were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). We analyzed the association between the ΔNp63 and ΔN/TAp63 mRNA expression ratio and clinicopathological parameters and compared disease-specific survival of each ΔNp63 mRNA expression and ΔN/TAp63 mRNA expression ratio. The ΔN/TAp63 mRNA expression ratio in cervical cancer showed higher sensitivity than the mRNA expression levels of ΔNp63 (52.0% vs 44.2%). The level of ΔN/TAp63 mRNA expression ratio in precancerous LSIL and HSIL was higher than in normal tissues (P = 0.01 and P = 0.003) and lower than in cervical cancer tissues (P = 0.03 and P = 0.02). Besides, the positive ΔN/TAp63 mRNA expression ratio was associated with bulky tumor size and high expression of Ki-67, the proliferation marker, in cervical cancer (P = 0.04 and P = 0.02). The cervical cancer patients with the positive ΔN/TAp63 mRNA expression ratio showed worse survival compared to those who with the negative expression ratio of ΔN/TAp63 (HR = 5.7, 95% CI: 1.6-19.9). In conclusion, the balance of TAp63 and ΔNp63 is closely related to the carcinogenesis of cervical cancer. The ΔN/TAp63 mRNA expression ratio could be useful as a diagnostic and prognostic marker of cervical cancer.

摘要

p63 是 p53 家族的转录因子。已报道 p63 有两种主要的异构体,即具有转录激活(TA)结构域的 TAp63 和具有截断 TA 结构域的 ΔNp63,它们在肿瘤抑制或致癌功能中发挥相反的作用。关于这两种 p63 异构体在宫颈癌发生中的关联知之甚少。在这项研究中,使用定量逆转录聚合酶链反应(RT-qPCR)检测了 40 例正常、30 例低级别鳞状上皮内病变(LSIL)、38 例高级别鳞状上皮内病变(HSIL)和 52 例宫颈癌福尔马林固定石蜡包埋组织中 TAp63 和 ΔNp63 的 mRNA 表达水平。我们分析了 ΔNp63 与 ΔN/TAp63 mRNA 表达比值与临床病理参数之间的关系,并比较了每个 ΔNp63 mRNA 表达和 ΔN/TAp63 mRNA 表达比值的疾病特异性生存情况。宫颈癌中 ΔN/TAp63 mRNA 表达比值的敏感性高于 ΔNp63 的 mRNA 表达水平(52.0%比 44.2%)。癌前病变 LSIL 和 HSIL 中 ΔN/TAp63 mRNA 表达比值高于正常组织(P=0.01 和 P=0.003),低于宫颈癌组织(P=0.03 和 P=0.02)。此外,阳性 ΔN/TAp63 mRNA 表达比值与宫颈癌中大块肿瘤大小和增殖标志物 Ki-67 的高表达相关(P=0.04 和 P=0.02)。与 ΔN/TAp63 mRNA 表达比值阴性的宫颈癌患者相比,阳性 ΔN/TAp63 mRNA 表达比值的宫颈癌患者生存较差(HR=5.7,95%CI:1.6-19.9)。总之,TAp63 和 ΔNp63 的平衡与宫颈癌的发生密切相关。ΔN/TAp63 mRNA 表达比值可作为宫颈癌的诊断和预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d886/6459502/8d9e3394cc18/pone.0214867.g001.jpg

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