Zhang Kai, Li Huiyang, Yan Ye, Zang Yuqin, Li Ke, Wang Yingmei, Xue Fengxia
Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Oncol Lett. 2019 Sep;18(3):2464-2476. doi: 10.3892/ol.2019.10550. Epub 2019 Jun 28.
Endometrial carcinoma (EC) is a common malignant neoplasm of the female reproductive tract. The malignant degree of type II EC is much greater than that of type I EC, usually presenting with a high recurrence rate and a poor prognosis. Therefore, the present study aimed to examine the principal genes associated with the degree of differentiation in type I and type II EC and reveal their potential mechanisms. Differentially expressed genes (DEGs) were selected from the gene expression profiles derived from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In the present study, the KEGG pathway enrichment analysis revealed that 5,962 upregulated DEGs were significantly enriched in the 'p53 signaling pathway' and involved in 'lysine degradation'. In addition, 3,709 downregulated DEGs were enriched in 'pathways in cancer', as well as 'tight junction regulation', the 'cell cycle' and the 'Wnt signaling pathway'. The 13 top hub genes MAPK1, PHLPP1, ESR1, MDM2, CDKN2A, CDKN1A, AURKA, BCL2L1, POLQ, PIK3R3, RHOQ, EIF4E and LATS2 were identified via the protein-protein interaction network. Furthermore, the OncoPrint algorithm from cBioPortal declared that 25% of EC cases carried genetic alterations. The altered DEGs (MAPK1, MDM2, AURKA, EIF4E and LATS2) may be involved in tumor differentiation and may be valuable diagnostic biomarkers. In conclusion, a number of principal genes were identified in the present study that may be determinants of poorly differentiated type II EC carcinogenesis, which may contribute to future research into potential molecular mechanisms. In addition, these genes may help identify candidate biomarkers and novel therapeutic targets for type II EC.
子宫内膜癌（EC）是女性生殖道常见的恶性肿瘤。II型EC的恶性程度远高于I型EC，通常具有高复发率和不良预后。因此，本研究旨在检测与I型和II型EC分化程度相关的主要基因，并揭示其潜在机制。从癌症基因组图谱获得的基因表达谱中筛选差异表达基因（DEG）。进行基因本体论和京都基因与基因组百科全书（KEGG）通路富集分析。在本研究中，KEGG通路富集分析显示，5962个上调的DEG在“p53信号通路”中显著富集，并参与“赖氨酸降解”。此外，3709个下调的DEG在“癌症通路”以及“紧密连接调节”、“细胞周期”和“Wnt信号通路”中富集。通过蛋白质-蛋白质相互作用网络鉴定出13个顶级枢纽基因，即MAPK1、PHLPP1、ESR1、MDM2、CDKN2A、CDKN1A、AURKA、BCL2L1、POLQ、PIK3R3、RHOQ、EIF4E和LATS2。此外，cBioPortal的OncoPrint算法表明，25%的EC病例存在基因改变。改变的DEG（MAPK1、MDM2、AURKA、EIF4E和LATS2）可能参与肿瘤分化，可能是有价值的诊断生物标志物。总之，本研究鉴定出一些主要基因，它们可能是低分化II型EC致癌作用的决定因素，这可能有助于未来对潜在分子机制的研究。此外，这些基因可能有助于识别II型EC的候选生物标志物和新的治疗靶点。
