Comprehensive and Integrative Analysis Reveals the Diagnostic, Clinicopathological and Prognostic Significance of Polo-Like Kinase 1 in Hepatocellular Carcinoma.

Abstract

BACKGROUND/AIMS:

Liver cancer has the second highest cancer-related death rate globally and has relatively few targeted therapeutics. Polo-like kinase 1 (PLK1) is a fascinating trigger of the cell cycle; however, the still-rudimentary understanding of PLK1 at present is a significant barrier to its clinical applications. Here, we comprehensively clarified the clinicopathological value and potential functions of PLK1 in hepatocellular carcinoma (HCC).

METHODS:

HCC-related microarrays, RNA-sequencing datasets and published studies were deeply mined and integrated from The Cancer Genome Atlas, Gene Expression Omnibus, ArrayExpress, Oncomine, literature databases, and immunohistochemistry experiments. Meanwhile, the associations between PLK1 expression and its clinicopathological implications and prognostic value in HCC patients were assessed. The standardized mean difference, summary receiver operating characteristic curve and the corresponding area under the curve, hazard ratios, odds ratios (ORs), and their 95% confidence intervals (CIs) were examined by STATA 12.0. Additionally, several bioinformatics methods were used to identify the potential function of PLK1 in HCC.

RESULTS:

Comprehensive analyses revealed that PLK1 was significantly increased in HCC (standardized mean difference = 1.34, 95% CI: 1.03-1.65, P < 0.001). The results of diagnostic tests specified that in the summary receiver operating characteristic curve, the area under the curve was 0.88 (95% CI: 0.85-0.90). Furthermore, an elevated PLK1 level significantly predicted unfavorable overall survival (hazard ratio = 1.78, 95% CI: 1.10-2.88, P = 0.019) and was correlated with female gender (OR = 0.73, 95% CI: 0.56-0.95, P = 0.017), tumor thrombus (OR = 3.97, 95% CI: 1.46-10.78, P < 0.001), metastasis (OR = 3.46, 95% CI: 1.33-9.01, P = 0.011), pathologic stage (OR = 1.56, 95% CI: 1.17-2.07, P = 0.002), Barcelona Clinic Liver Cancer stage (OR = 5.76, 95% CI: 2.17-15.28, P < 0.001) and histologic grade (OR = 2.33, 95% CI: 1.12-487, P = 0.024). Through bioinformatics methods, we determined that enhancing the proliferative effect of PLK1 in HCC was associated with a series of hub genes and the activation of the cell cycle pathway.

CONCLUSIONS:

These findings substantiated that PLK1 may be an independent prognostic biomarker in HCC and may facilitate the development of targeted precision oncology.

• Authors: Peng Lin, Dong-Yue Wen, Yi-Wu Dang, Yun He, Hong Yang, Gang Chen
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 47 Issue 3 Pg. 925-947 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29843122 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• Proto-Oncogene Proteins
• Protein Serine-Threonine Kinases

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Hepatocellular (diagnosis, enzymology, genetics, mortality)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Computational Biology
• Humans
• Liver Neoplasms (diagnosis, enzymology, genetics, mortality)
• Prognosis
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• Polo-Like Kinase 1