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JAK/STAT pathway transmits signals from the cell membrane to the nucleus in response to extracellular growth factors and cytokines. Activation of this pathway has been found in certain types of human tumors. The goal of this study was to investigate the correlation between the JAK/STAT pathway in human gliomas and patients' prognosis, which currently is unknown. Western blotting analysis and immunohistochemical staining were performed to detect JAK-1, phosphorylated JAK-1, and STAT-3 expression patterns in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Western blotting analysis and immunohistochemical staining both indicated that the expression levels of JAK-1, phosphorylated JAK-1, and STAT-3 in primary glioma tissues were significantly higher than those in normal brain tissues (P < 0.001). Especially, the positive expression rates of JAK-1, phosphorylated JAK-1, and STAT-3 were significantly higher in patients with higher grade (P = 0.001, 0.001, and 0.002, respectively) and lower KPS score (P = 0.01, 0.008, and 0.01, respectively). Statistical analysis showed that patients with gliomas expressing JAK-1 and STAT-3 have lower overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.03), WHO grade (P = 0.008), JAK-1 (P = 0.005), and STAT-3 (P = 0.006) were independent prognosis factors for human gliomas. These results provide convincing evidence for the first time that the JAK/STAT pathway may play a role in the progression of human gliomas. Its activated state might be a potent tool for predicting the clinical prognosis of patients with glioma.

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Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a microtubule-associated protein that regulates spindle assembly in human cells and is overexpressed in various malignancies. However, the role of NEK2 in hepatocellular carcinoma (HCC) remains undetermined. We performed RNA-seq of the HCC cell line SMMC-7721 and the normal liver cell line HL-7702 using the Ion Proton System. NEK2 expression was detected using quantitative reverse transcription polymerase chain reaction in two cell lines and 5 matched HCC and adjacent non-tumorous liver tissues. The correlation between survival and NEK2 expression was analyzed in 359 patients with HCC using RNASeqV2 data available from The Cancer Genome Atlas (TCGA) website (https://tcga-data.nci.nih.gov/tcga/). The expression of NEK2, phospho-AKT and MMP-2 was evaluated by immunohistochemistry in 63 cases of HCC and matched adjacent non-tumorous liver tissues. Relationships between protein expression and clinicopathological parameters were assessed, and the correlations between NEK2 with phospho-AKT and MMP-2 expressions were evaluated. A total of 610 differentially expressed genes (DEGs) were revealed in the transcriptome comparison, 297 of which were upregulated and 313 were downregulated in HCC. NEK2, as the most obviously different DEG in cells and tissues from the RNA-seq data, was listed as an HCC candidate biomarker for further verification. NEK2 was overexpressed in HCC cells and tissues (P=0.002, P=0.013) and HCC patients with a high expression of NEK2 had a poor prognosis (P=0.0145). Clinical analysis indicated that the overexpression of NEK2 in HCC was significantly correlated with diolame complete (P<0.001), tumor nodule number (P=0.012) and recurrence (P=0.004). NEK2 expression was positively correlated with the expression of phospho-AKT (r=0.883, P<0.01) and MMP-2 (r=0.781, P<0.01). Overexpression of NEK2 was associated with clinicopathological characteristics and poor patient outcomes, suggesting that NEK2 serves as a prognostic biomarker for HCC. Alteration of NEK2 protein levels may contribute to invasion and metastasis of HCC, which may occur through activation of AKT signaling and promotion of MMP-2 expression.

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