DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway.

Abstract

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.

• Authors: Meng Zhang, Yu Pan, Ranran Jiang, Pingfu Hou, Haixia Shan, Fang Chen, Tao Jiang, Jin Bai, Junnian Zheng
• Journal: Oncology reports (Oncol Rep) Vol. 40 Issue 2 Pg. 968-978 (Aug 2018) ISSN: 1791-2431 [Electronic] Greece
• PMID: 29901172 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• DKC1 protein, human
• Nuclear Proteins
• Transcription Factor RelA
• Matrix Metalloproteinase 2

Topics

• Animals
• Biomarkers, Tumor (genetics)
• Carcinoma, Renal Cell (genetics, pathology)
• Cell Cycle Proteins (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Kidney Neoplasms (genetics, pathology)
• Male
• Matrix Metalloproteinase 2 (genetics)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Neoplasm Invasiveness (genetics, pathology)
• Nuclear Proteins (genetics)
• Prognosis
• Signal Transduction (genetics)
• Transcription Factor RelA (genetics)
• Up-Regulation (genetics)