Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea.
Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea.
Pathol Res Pract. 2020 Apr;216(4):152880. doi: 10.1016/j.prp.2020.152880. Epub 2020 Feb 13.
The derangement of the cell cycle facilitates uncontrolled cell proliferation and acquisition of genetic alterations favorable for malignancy. However, the protein expression profiles of E2 F family cell cycle regulators in clear cell renal cell carcinoma (ccRCC) have not yet been thoroughly investigated. In this study, we aimed to examine the protein expression profiles and prognostic value of E2 F1, E2 F3, and E2 F4 in ccRCC cases. The immunohistochemical expression of E2 F1, E2 F3, and E2 F4 was quantitatively scored in 180 ccRCC tumor tissues and 79 normal kidney tissues. The prognostic implications of these E2 F members were determined. We found that ccRCC tumor cells showed higher nuclear expression of E2 F1, E2 F3 and E2 F4 than normal kidney samples. High E2 F1 and E2 F3 expression in tumor cells was associated with poor prognostic factors of ccRCC, whereas high E2 F4 correlated with beneficial prognostic factors. High expression of E2 F1 and E2 F3 in tumor cells was correlated with a poor overall and recurrence-free survival, while high E2 F4 expression did not. In conclusion, E2 F1, E2 F3 and E2 F4 may function as oncogenes during tumorigenesis of ccRCC, although they contribute to the progression of ccRCC in different ways. Additional studies are required to clarify the conflicting role of E2 F4 in the tumor evolution of ccRCC.
细胞周期失调促进了不受控制的细胞增殖和获得有利于恶性肿瘤的遗传改变。然而，尚未彻底研究 E2F 家族细胞周期调节剂在透明细胞肾细胞癌 (ccRCC) 中的蛋白表达谱。在本研究中，我们旨在研究 E2F1、E2F3 和 E2F4 在 ccRCC 病例中的蛋白表达谱和预后价值。在 180 例 ccRCC 肿瘤组织和 79 例正常肾脏组织中定量评分 E2F1、E2F3 和 E2F4 的免疫组织化学表达。确定这些 E2F 成员的预后意义。我们发现 ccRCC 肿瘤细胞的核 E2F1、E2F3 和 E2F4 表达高于正常肾脏样本。肿瘤细胞中高 E2F1 和 E2F3 表达与 ccRCC 的不良预后因素相关，而 E2F4 高表达与有利的预后因素相关。肿瘤细胞中 E2F1 和 E2F3 的高表达与整体和无复发生存率差相关，而 E2F4 的高表达则不然。总之，E2F1、E2F3 和 E2F4 可能在 ccRCC 发生过程中作为癌基因发挥作用，尽管它们以不同的方式促进 ccRCC 的进展。需要进一步的研究来阐明 E2F4 在 ccRCC 肿瘤进化中的矛盾作用。
