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Downregulated DYRK2 expression is associated with poor prognosis and Oxaliplatin resistance in hepatocellular
Xiubing Zhang1, Pan Xu2, Wenkai Ni3
1Department of Medical Oncology, the Second Peoples Hospital of Nan Tong, 43 Tangzha Xinglong Road, Nantong 226002, Jiangsu Province, People's Republic of China.
Abstract:
We aimed to investigate the molecular mechanisms of DYRK2 and the HCC sensitivity to Oxaliplatin in DYRK2-depleted HCC cells. HCC tissue specimens were obtained from 86 HCC patients during hepatectomy. We used immunohistochemistry and western blot to analyze DYRK2 expression in HCC tissues and cell lines, and used siRNA transfection to decrease DYRK2 expression in HCC cells. Flow cytometry and CCK-8 assay were detected in cell cycle progression, cell proliferation and the efficacy of Oxaliplatin, DYRK2 was down-regulated in HCC tissues, compared with adjacent nontumor ones. The significant correlation between DYRK2 expression and clinicopathologic factors was apparently shown in the immunohistochemical and statistical analyses. The expression of DYRK2 was significantly associated with histological grade of HCC patients. Univariate and multivariate survival analyses revealed that DYRK2 was a significant predictor for overall survival of HCC patients. The depletion of DYRK2 promoted HCC cell proliferation, and increased resistance to Oxaliplatin. These data showed that the downregulated expression of DYRK2 in HCC tumor tissues could promote the proliferation of HCC cells. In addition, reducing DYRK2 expression was associated with poor prognosis and Oxaliplatin resistance in HCC.
Insights
Downregulated DYRK2 expression in hepatocellular carcinoma (HCC) promotes tumor growth and resistance to Oxaliplatin chemotherapy. Reduced DYRK2 indicates a poor prognosis for HCC patients, impacting survival and treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Hepatology
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Understanding the molecular drivers of HCC progression and drug resistance is crucial for improving patient outcomes.
- DYRK2 (Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 2) role in HCC is not fully elucidated.
Purpose of the Study:
- To investigate the molecular mechanisms of DYRK2 in HCC.
- To determine the impact of DYRK2 depletion on HCC cell sensitivity to Oxaliplatin.
- To correlate DYRK2 expression with clinicopathological features and prognosis in HCC patients.
Main Methods:
- Analysis of DYRK2 expression in 86 HCC tissue specimens using immunohistochemistry and western blot.
- siRNA-mediated depletion of DYRK2 in HCC cell lines.
- Assessment of cell cycle, proliferation, and Oxaliplatin efficacy via flow cytometry and CCK-8 assay.
- Statistical analysis including survival analysis.
Main Results:
- DYRK2 was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues.
- Lower DYRK2 expression correlated with higher histological grade and predicted poor overall survival in HCC patients.
- DYRK2 depletion promoted HCC cell proliferation and increased resistance to Oxaliplatin treatment.
Conclusions:
- Downregulation of DYRK2 in HCC tissues promotes tumor cell proliferation.
- Reduced DYRK2 expression is associated with poor prognosis and Oxaliplatin resistance in HCC.
- DYRK2 may serve as a potential therapeutic target or prognostic biomarker in HCC.
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