Up-Regulated Maternal Embryonic Leucine Zipper Kinase Predicts Poor Prognosis of Hepatocellular Carcinoma Patients in a Chinese Han Population

Med Sci Monit. 2017 Dec 1:23:5705-5713. doi: 10.12659/msm.907600.

Abstract

BACKGROUND Maternal embryonic leucine zipper kinase (MELK) has been implicated in various types of tumors, but its expression profile and clinicopathologic significance in hepatocellular carcinoma (HCC) in Chinese Han people remains unknown. Therefore, this study attempted to investigate the expression pattern of MELK in HCC tissues obtained from a Chinese Han population. MATERIAL AND METHODS The expression of MELK, from RNA to protein levels, in HCC or disease-free human liver tissues was evaluated using quantitative real-time polymerase chain reaction assays and immunohistochemistry staining, and its prognostic significance was determined based on its impact on HCC patients' survival. RESULTS We found that HCC tissues expressed a higher level of MELK RNA than non-tumor tissues in tumor-related public databases (P<0.001). Hence, we assessed MELK mRNA expression within 32 HCC samples and their adjacent non-tumorous liver tissues in our center. Subsequently, MELK protein expression was evaluated within 101 HCC specimens and 40 disease-free liver tissues. Notably, it revealed that high MELK protein expression was significantly related with tumor number, tumor size, higher pathological tumor-nodule-metastasis stage, vascular invasion, and recurrence (P<0.05, all). Furthermore, elevated MELK protein expression was correlated with decreased overall survival and disease-free survival (P=0.004 and P=0.002, respectively). Univariate and multivariate analysis results show that MELK protein may serve as an independent prognostic indicator for determining prognosis of HCC patients. CONCLUSIONS We found that, in a Chinese Han population, MELK was highly expressed within HCC tissues from RNA to protein levels, and may be a potential independent prognostic biomarker for HCC patients.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • China / epidemiology
  • Disease-Free Survival
  • Ethnicity / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Serine-Threonine Kinases / physiology*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction / methods
  • Transcriptional Activation
  • Transcriptome / genetics
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • MELK protein, human
  • Protein Serine-Threonine Kinases