Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Oncol Rep. 2018 Aug;40(2):968-978. doi: 10.3892/or.2018.6484. Epub 2018 Jun 11.
DKC1, an X‑linked gene encoding dyskerin at Xq28, is a crucial component of the telomerase complex and is indispensable for normal telomere function and the post‑-transcriptional modification of precursor rRNA. It has been revealed to exert diverse biological functions and prognostic values in numerous types of cancers. Our present study was aimed at examining DKC1 expression in normal renal tissues and clear cell renal cell carcinoma (ccRCC) samples and the prognostic value of DKC1 in ccRCC. We examined DKC1 protein expression levels in tissue microarrays including 307 cases of ccRCC tissues and in 75 pairs of ccRCC and paracancerous tissues with immunohistochemistry. The percentage of DKC1 expression in ccRCC (61.3%) was markedly higher than that in paracancerous tissues (34.7%) (P=0.001). Positive DKC1 expression tends to significantly be associated with unfavorable clinicopathological characteristics such as tumor diameter >7 cm (P=0.002) and tumor‑node‑metastasis (TNM) stage III or IV (P<0.001). Multivariate COX analysis revealed that positive DKC1 expression was an independent unfavorable factor for prognosis of ccRCC patients [hazard ratio (HR)=1.932, 95% CI, 1.290‑2.893, P=0.001 for 5‑year overall survival; HR=1.778, 95% CI,1.150‑2.748, P=0.010 for disease‑free survival]. In the PROGgeneV2 platform, we also found that ccRCC patients with high DKC1 mRNA expression had a poorer prognosis than patients with low DKC1 expression in The Cancer Genome Atlas (TCGA). Furthermore, we found that knockdown of DKC1 inhibited proliferation, migration and invasion of ccRCC through regulation of the NF‑κB/MMP‑2 signaling pathway in vitro. We also demonstrated that DKC1 regulated ccRCC proliferation and the expression of NF‑κB‑p65 and MMP‑2 in vivo. In summary, the expression of DKC1 was upregulated in ccRCC, which was associated with unfavorable clinicopathological characteristics and DKC1 may act as an independent prognostic indicator of ccRCC patients.
DKC1 是一个位于 Xq28 的 X 连锁基因,编码端粒酶复合物中的 dyskerin,是端粒酶功能和前体 rRNA 转录后修饰所必需的关键成分。已经揭示它在许多类型的癌症中具有多种生物学功能和预后价值。本研究旨在检测正常肾组织和透明细胞肾细胞癌(ccRCC)样本中的 DKC1 表达,并研究 DKC1 在 ccRCC 中的预后价值。我们使用免疫组织化学法在包括 307 例 ccRCC 组织的组织微阵列和 75 对 ccRCC 和癌旁组织中检测了 DKC1 蛋白的表达水平。ccRCC 中 DKC1 的表达百分比(61.3%)明显高于癌旁组织(34.7%)(P=0.001)。阳性 DKC1 表达与不利的临床病理特征显著相关,例如肿瘤直径>7cm(P=0.002)和 TNM 分期 III 或 IV 期(P<0.001)。多变量 COX 分析显示,阳性 DKC1 表达是 ccRCC 患者预后的独立不利因素[风险比(HR)=1.932,95%置信区间,1.290-2.893,P=0.001,用于 5 年总生存率;HR=1.778,95%置信区间,1.150-2.748,P=0.010,用于无病生存率]。在 PROGgeneV2 平台上,我们还发现,在癌症基因组图谱(TCGA)中,DKC1 mRNA 表达较高的 ccRCC 患者预后较 DKC1 表达较低的患者差。此外,我们发现,在体外通过调节 NF-κB/MMP-2 信号通路,DKC1 的敲低抑制了 ccRCC 的增殖、迁移和侵袭。我们还证明,DKC1 在体内调节 ccRCC 的增殖以及 NF-κB-p65 和 MMP-2 的表达。总之,DKC1 在 ccRCC 中表达上调,与不利的临床病理特征相关,并且 DKC1 可能是 ccRCC 患者的独立预后指标。