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PLK1/2/3/4 在肺腺癌和肺鳞癌中的鉴定和评估:来自甲基化谱的证据。

Identification and assessment of PLK1/2/3/4 in lung adenocarcinoma and lung squamous cell carcinoma: Evidence from methylation profile.

机构信息

Cancer Center, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.

Department of Orthopedics, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Cell Mol Med. 2021 Jul;25(14):6652-6663. doi: 10.1111/jcmm.16668. Epub 2021 Jun 2.

Abstract

Lung cancer is a very aggressive cancer characterized with molecular heterogeneities in different subtypes, including lung adenocarcinoma and lung squamous cell carcinoma. However, few related molecular signatures have been established for the treatment of lung cancer subtypes. Polo-like kinase (PLK) family is a crucial regulator during cell division. Aberrant genetic and epigenetic alteration of PLK members plays a controversial role among different cancers. In this study, we performed an analysis of transcriptional and protein expression to identify overexpressed PLK1/4 and under-expressed PLK2/3 in lung cancer subtypes. We then analysed biological function of PLKs and related genes. Besides, we estimated a correlation of PLKs with patient's genders and TP53 mutation in lung cancer. Higher PLK1/4 expression was significantly associated with male patient and TP53 mutant status, separately. Moreover, we carried out a methylation profile analysis including methylation level, DNA methyltransferases correlation and survival analysis of global methylation. Global methylation survival analysis showed that prognostic value of PLK1/2/4 methylation remained the same significant trend between two lung cancer subtypes, whereas prognostic value of PLK3 methylation lacked consistency. Taken together, these results provided instructive insights into a comprehensive evaluation for advanced therapeutic strategy based on epigenetic evidences.

摘要

肺癌是一种非常侵袭性的癌症,具有不同亚型的分子异质性,包括肺腺癌和肺鳞状细胞癌。然而,针对肺癌亚型的治疗,相关的分子特征很少被建立。Polo 样激酶(PLK)家族是细胞分裂过程中的关键调节因子。PLK 成员的异常遗传和表观遗传改变在不同癌症中发挥着争议性的作用。在这项研究中,我们进行了转录和蛋白质表达分析,以鉴定肺癌亚型中过表达的 PLK1/4 和低表达的 PLK2/3。然后,我们分析了 PLKs 及其相关基因的生物学功能。此外,我们还评估了 PLKs 与肺癌患者性别和 TP53 突变之间的相关性。PLK1/4 的高表达与男性患者和 TP53 突变状态显著相关。此外,我们进行了甲基化谱分析,包括甲基化水平、DNA 甲基转移酶相关性和全基因组甲基化的生存分析。全基因组甲基化生存分析表明,PLK1/2/4 甲基化的预后价值在两种肺癌亚型之间仍然具有相同的显著趋势,而 PLK3 甲基化的预后价值缺乏一致性。总之,这些结果为基于表观遗传学证据的综合评估提供了有价值的见解,以制定更先进的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e65/8278123/af8e2f1ecc1b/JCMM-25-6652-g005.jpg

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