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

Abstract

BackgroundMaternal 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/MethodsThe 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.ResultsWe 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.ConclusionsWe 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.

Maternal Embryonic Leucine Zipper Kinase Promotes Tumor Growth and Metastasis via Stimulating FOXM1 Signaling in Esophageal Squamous Cell Carcinoma

“…Overexpression of MELK was also associated with distant metastasis, lymph node involvement and poor prognosis in GC patients (17). In HCC, high MELK protein expression was not only related with short disease-free survival and overall survival but also correlated with vascular invasion and higher pathological tumor-nodule-metastasis stage (16). Consistently, we observed that the expression of MELK was much higher in metastatic ESCC tissues, compared to that from primary tumors.…”

“…Furthermore, elevated MELK protein expression was correlated with decreased overall survival and disease-free survival in various types of human cancer (9,(17)(18)(19). Notably, it revealed that high MELK protein expression was also significantly associated with higher pathological tumor-nodule-metastasis stage, vascular invasion (16). Moreover, the abnormal expression of MELK was related to cervical cancer metastasis at early stage (9).…”

“…By using bioinformatic and oligonucleotide microarray analyses to compare gene expression between human normal and tumor tissues, Gray et al provided evidence that MELK expression was elevated in 13, 23, and 96% of ovarian, lung and colorectal tumor samples, respectively (15). The expression of MELK was also upregulated in other human malignant tumors such as hepatocellular carcinoma (HCC) (16), gastric cancer (GC) (17), neuroblastoma (18,19) and breast cancer (20)(21)(22). High MELK protein expression was significantly related with tumor number, tumor size and recurrence.…”

Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer

“…Over expression of MELK is associated with a poor prognosis in several malignancies . In breast and gastric cancers, the expression of MELK correlated with the metastasis and recurrence of tumors.…”

Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target in lung adenocarcinoma

“…MELK has been reported to participate in tumour progression via the JNK, p53, Bcl-G and forkhead box protein M1 (FOXM1) signalling pathways, which are all extremely important in multiple human cancer types (8,(25)(26)(27)(28). Gu et al (28) indicated that MELK regulates glioma cell growth via the JNK/p53 pathway.…”