High STAT4 Expression is a Better Prognostic Indicator in Patients with Hepatocellular Carcinoma After Hepatectomy

Wubetu, Gizachew Yismaw; Utsunomiya, Tohru; Ishikawa, Daichi; Yamada, Shinichiro; Ikemoto, Tetsuya; Morine, Yuji; Iwahashi, Shuichi; Saito, Yu; Arakawa, Yusuke; Imura, Satoru; Kanamoto, Mami; Zhu, Chunhui; Bando, Yoshimi

doi:10.1245/s10434-014-3861-9

Cited by 35 publications

(48 citation statements)

References 37 publications

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“…Therefore, STAT4 in hepatocytes may exert a suppressive effect on the development of HCC tumors. Other studies have shown that the role of STAT4 in the prevention of liver disease was related to inflammatory pathways . Hepatocellular carcinoma is the third most common cause of cancer death worldwide.…”

Section: Discussionmentioning

confidence: 99%

Meta‐analysis reveals an association between signal transducer and activator of transcription‐4 polymorphism and hepatocellular carcinoma risk

Zhang

Liu

et al. 2016

Hepatology Research

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Section: Discussionmentioning

confidence: 99%

Meta‐analysis reveals an association between signal transducer and activator of transcription‐4 polymorphism and hepatocellular carcinoma risk

Zhang

Liu

et al. 2016

Hepatology Research

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“…In the full-text review of the remaining 14 articles, 4 studies were further excluded since the articles did not provide extractable data. Finally, 10 previously published articles and our current cohort study were included in the meta-analysis [25,30,32,[39][40][41][42][43][44][45]. The details of the literature selection process are presented in Fig.…”

Section: Study Search and Study Characteristics In Meta-analysismentioning

confidence: 99%

“…All reports were published between 2016 and 2018. In addition to our cohort study, 9 of the previous studies were conducted in China [25,32,[39][40][41][42][43][44][45], and 1 in Japan [30]. The case numbers in each study ranged between [30,32,39,42,45], and 5 referring to liver cirrhosis [32,41,42,44,45].…”

Section: Study Search and Study Characteristics In Meta-analysismentioning

confidence: 99%

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The Prognostic Significance of NEK2 in Hepatocellular Carcinoma: Evidence from a Meta-Analysis and Retrospective Cohort Study

Cheng

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Numerous studies have shown that NIMA-related kinase 2 (NEK2) expression in hepatocellular carcinoma (HCC) tissue is associated with survival and clinicopathological features; however, the evidence remains inconclusive. Thus, we aimed to further explore the prognostic and clinicopathological significance of NEK2 expression in HCC using a two-part study consisting of a retrospective cohort study and a meta-analysis. Methods: In the cohort study, NEK2 expression in 206 HCC samples and adjacent normal liver tissues was detected by immunohistochemistry (IHC). Patients were divided into a high NEK2 expression group and a low NEK2 expression group by the median value of the immunohistochemical scores. The Kaplan–Meier method with the log-rank test was used to analyze survival outcomes in the two groups, and multivariate analysis based on Cox proportional hazard regression models was applied to identify independent prognostic factors. In the meta-analysis, eligible studies were searched in PubMed, EMBASE, Web of Science, and CNKI databases. STATA version 12.0 (Stata Corporation, College Station, TX) was used for statistical analyses. Results: The IHC results of our cohort study showed higher NEK2 expression in HCC tissues compared with adjacent normal liver tissues. Multivariate analysis revealed that high NEK2 expression was an independent risk factor for poor overall survival (OS) [hazard ratio (HR) = 1.763; 95% CI, 1.060–2.935; P = 0.029] and disease-free survival (DFS) [hazard ratio (HR) = 1.687; 95% CI, 1.102–2.584; P = 0.016] in HCC patients. A total of 11 studies with 1,698 patients were enrolled in the meta-analysis, consisting of 10 studies from the database search and our cohort study. The pooled results revealed that high NEK2 expression correlated closely with poor OS among HCC patients (HR = 1.47; 95% CI, 1.21–1.80; P < 0.01), and DFS/recurrence-free survival (RFS) (HR = 1.92; 95% CI, 1.41–2.63; P < 0.01). Additionally, our meta-analysis also showed that the proportion of HCC patients with high NEK2 expression was greater in the group with larger tumors (> 5 cm) than in the group with smaller tumors (≤ 5 cm) [odds ratio (OR) = 2.02; 95% CI, 1.13–3.64; P < 0.01). Conclusion: Our study demonstrated that high NEK2 expression is a risk factor for poor survival in HCC patients. More prospective, homogeneous, and multiethnic studies are required to validate our findings.

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“…For instance, in a previous study, miR‐128 played an essential role in inhibiting colorectal cancer cell proliferation by regulating NEK2 . High NEK2 expression was a tumor recurrence predictor for patients after hepatectomy treatment and an NEK2 small interfering (si)RNA injection inhibited cancer cell proliferation and peritoneal dissemination of cholangiocarcinoma in a mouse model . Furthermore, the combination of NEK2 siRNA and the chemotherapeutic agent cisplatin could enhance colorectal cancer cell apoptosis and death, suggesting an optional therapeutic approach for cancer treatment .…”

Section: Introductionmentioning

confidence: 98%

MicroRNA‐128 promotes apoptosis in lung cancer by directly targeting NIMA‐related kinase 2

et al. 2017

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BackgroundMicroRNA‐128 (miR‐128) serves as a regulator by inducing cancer cell apoptosis, differentiation, the epithelial‐to‐mesenchymal transition process, and tumor growth by mediating different targets. NIMA‐related kinase 2 (NEK2) is aberrantly expressed in lung cancer. The miR‐128/NEK2 pathway has been reported to predict prognosis in colorectal cancer; however, the determination of a relationship between miR‐128 and NEK2 in lung cancer has remained elusive. We explored the association between miR‐128 and NEK2 in lung cancer.MethodsMiR‐128 and NEK2 expression were examined in 15 lung cancer tissues by real time‐PCR. Lung cancer SK‐MES‐1 cells were transfected with miR‐128 mimic, an inhibitor or a negative control. MiR‐128 and NEK2 expression levels were detected using quantitative real time‐PCR and Western blot. SK‐MES‐1 cell apoptosis was performed by flow cytometry.ResultsCompared to adjacent non‐tumor tissues, miR‐128 was downregulated and NEK2 was upregulated in 15 lung cancer tissues. Lung cancer SK‐MES‐1 cells transfected with miR‐128 mimic induced a higher apoptotic rate than those transfected with the negative control. Dual luciferase assay further confirmed that NEK2 was a direct target of miR‐128 in lung cancer, and transfection with miR‐128 mimic could decrease the NEK2 protein level while the miR‐128 inhibitor increased NEK2 expression. Finally, the apoptotic effect of lung cancer cells induced by miR‐128 mimic could be reversed by NEK2 overexpression.Conclusions NEK2 was regulated by miR‐128 in lung cancer and miR‐128 induced lung cancer cell apoptosis by mediating NEK2 expression.

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High STAT4 Expression is a Better Prognostic Indicator in Patients with Hepatocellular Carcinoma After Hepatectomy

Abstract: Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.

Cited by 35 publications

References 37 publications

Meta‐analysis reveals an association between signal transducer and activator of transcription‐4 polymorphism and hepatocellular carcinoma risk

Meta‐analysis reveals an association between signal transducer and activator of transcription‐4 polymorphism and hepatocellular carcinoma risk

The Prognostic Significance of NEK2 in Hepatocellular Carcinoma: Evidence from a Meta-Analysis and Retrospective Cohort Study

MicroRNA‐128 promotes apoptosis in lung cancer by directly targeting NIMA‐related kinase 2

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