Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India; Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Gene. 2020 May 20;739:144498. doi: 10.1016/j.gene.2020.144498. Epub 2020 Feb 22.
Clear cell renal cell carcinoma (ccRCC) is one of the deadly diseases with poor metastatic disease prognosis. There is an urgent need to explore the potential molecular markers which can improve the prognosis of the disease. Histone demethylases have emerged as a powerful tool for cancer prognosis and therapeutics during the last decade. The implications of demethylases of histone 3 lysine 4 (H3K4) in ccRCC are however unrevealed. We therefore evaluated the expression of H3K4 demethylases in ccRCC, with emphasis on their clinical significance as a prognostic marker.
Total 50 histopathological confirmed cases of ccRCC were enrolled in the study. The expression of seven H3K4 demethylases was determined by Real-Time PCR using gene specific primers and correlated with tumor stage, grade and metastasis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prognostic significance of H3K4 demethylases.
The median age of the patients was 54 years with predominance of male patients by 2.6-fold. Among seven genes viz FBXL10, LSD1, LSD2, KDM5A, KDM5B, KDM5C and KDM5D analyzed, LSD2 was found to be significantly associated with tumor stage and metastasis. The optimal cut-off value for LSD2 was 3.2 as calculated from ROC curve analysis for metastasis as well as TNM stage with area under curve of 0.74 and 0.78 respectively. In addition, LSD2 expression showed significant positive correlation with LSD1 expression in tumor metastasis.
The expression of LSD2 was associated with higher TNM stage and metastasis of the tumor and thus, might serve as a useful marker for ccRCC progression.
透明细胞肾细胞癌（ccRCC）是一种致命疾病，转移性疾病预后较差。迫切需要探索潜在的分子标志物，以改善疾病的预后。在过去十年中，组蛋白去甲基化酶已成为癌症预后和治疗的有力工具。然而，组蛋白 3 赖氨酸 4（H3K4）去甲基酶在 ccRCC 中的作用尚不清楚。因此，我们评估了 ccRCC 中 H3K4 去甲基酶的表达情况，并强调了其作为预后标志物的临床意义。
本研究共纳入 50 例经组织病理学证实的 ccRCC 病例。使用基因特异性引物通过实时 PCR 测定七种 H3K4 去甲基酶的表达，并与肿瘤分期、分级和转移相关联。进行Receiver operating characteristic（ROC）曲线分析以评估 H3K4 去甲基酶的预后意义。
患者的中位年龄为 54 岁，男性患者占 2.6 倍。在所分析的七个基因（FBXL10、LSD1、LSD2、KDM5A、KDM5B、KDM5C 和 KDM5D）中，LSD2 与肿瘤分期和转移显著相关。LSD2 的最佳截断值为 3.2，这是通过 ROC 曲线分析为转移和 TNM 分期计算得出的，曲线下面积分别为 0.74 和 0.78。此外，LSD2 表达与肿瘤转移中 LSD1 表达呈显著正相关。
LSD2 的表达与更高的 TNM 分期和肿瘤转移相关，因此可能成为 ccRCC 进展的有用标志物。
