Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma

Abstract

Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine protein kinase and belongs to the extracellular signal-regulated kinases/microtubule-associated protein kinase families (Erks/MAPKs). Previous studies have indicated that abnormal expressions of NLK played critical roles in various types of human cancers. Recent studies suggested that NLK expression was significantly upregulated in the hepatocellular carcinoma (HCC) specimens. However, the clinical significance of NLK expression in HCC remains largely unknown. In this study, we focused on the clinical significance of NLK in HCC and found that high expression of NLK was significantly associated with Edmondson-Steiner grade (P = 0.002), tumor size (P = 0.022), and no. of tumor nodules (P < 0.001), and NLK was positively correlated with proliferation marker Ki-67 (P < 0.01). Univariate analysis suggested that NLK expression was associated with poor prognosis (P < 0.001). Multivariate analysis indicated that NLK expression was an independent prognostic indicator for HCC (P = 0.0370). In conclusion, NLK overexpression is associated with poor overall survival in patients with HCC, it might be an independent poor prognostic marker for HCC.

Expression of Nemo-like kinase in cervical squamous cell carcinoma: a clinicopathological study

“…NLK has been demonstrated to correlate with histological grade, advanced stage, and lymph node metastasis. 14 , 15 , 17 , 21 Similarly, our study suggests that tumors with high NLK expression had greater invasive potential including vascular/lymphatic invasion. NLK overexpression was also observed in high-invasive regions such as metastatic lymph node.…”

“…Subcellular fractionation from COS7 cells and HEK293 cells verifies that ~60%–70% of NLK is localized in the nucleus and 30%–40% is localized in the cytoplasm. 20 NLK was predominantly located in the nucleus of tumor cells in nasopharyngeal carcinoma, hepatocellular carcinoma, glioma, and gallbladder cancer; 10 , 14 , 15 , 17 however, NLK was expressed mainly in the cytoplasm of tumor cells in colorectal cancer. 21 NLK-positive staining was confined mainly to the nucleus and cytoplasm in non-small-cell lung cancer (NSCLC).…”

MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST

“… 23 , 24 Unfortunately, there was no significant downregulation of DKK3 and NLK in HCC tissues compared with ANLTs (data not shown), which was consistent with the results from previous reports. 25 , 26 , 27 Neither DKK3 nor NLK had the inverse relationship with miR-92b expression in HCC tissues, implying DKK3 and NLK might not be key downstream targets of miR-92b in HCC progression. In view of the fact that one miRNA might downregulate large numbers of target genes by binding to complementary sequences in the 3′-UTR of target mRNAs, the downstream targets of a miRNA in one particular tissue or cell type should be determined by the gene expression patterns specific to the tissue or cell.…”

Gd-EOB-DTPA-enhanced magnetic resonance imaging combined with T1 mapping predicts the degree of differentiation in hepatocellular carcinoma

“…Previous studies have suggested that Edmondson-Steiner grade is an independent factor affecting prognosis/recurrence of HCC [ 15 – 20 ], which should be taken into account when considering therapeutic strategy [ 16 , 19 ]. In addition, liver cells take up Gd-EOB-DTPA via the receptors OATP1B1, OATP1B3 and NTCP.…”

“…It has been established that Edmondson-Steiner grade was an independent predictor for early recurrence in HCC. Furthermore, Edmondson-Steiner grade has been shown to be related to other markers of poor prognosis, including microvascular invasion [ 15 – 19 ], expression of Nemo-like kinase (NLK), Protein disulfide isomerase (PDI), p21-activated protein kinase (PAK) 6, chemokine receptor CCR9 [ 20 – 23 ].…”