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09 January 2019 : Clinical Research  

Prognostic Value of Upregulation of Myristoylated Alanine-Rich C-Kinase Substrate in Gastric Cancer

Ruiliang Quan1ABCDEFG*, Zhongliang Ning1BCD, Yongcang Wang1BCDF, Wei Yu1BCDEF, Haixing Zhu1BCDEFG

DOI: 10.12659/MSM.913558

Med Sci Monit 2019; 25:279-287

Abstract

BACKGROUND: Accumulating evidence suggests a connection of Myristoylated alanine-rich C-kinase substrate (MARCKS) with several physiological and pathological processes. However, the relevance of MARCKS in gastric cancer (GC) needs to be elucidated.

MATERIAL AND METHODS: The abundance of MARCKS in GC tissues was assessed using techniques of immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR). Moreover, the MARCKS expression profile in the TCGA database was analyzed through an online website analysis. We also investigated MARCKS function using cell wounding and Matrigel invasion assays.

RESULTS: TCGA analysis and our data suggest that transcript abundance and protein level of MARCKS was higher in GC tumor samples compared with peri-tumor tissues. There was a remarkable association of upregulated MARCKS with the cell differentiation (P<0.001), T stage (P=0.034), and N stage (P=0.002) followed by advanced TNM phase (P=0.008). Furthermore, it was predicted that higher expression of MARCKS is linked to poor overall survival (P=0.015) and disease-free survival (P=0.020), and that high levels of MARCKS function as an independent prognostic marker, as shown by multivariate Cox regression analysis in prediction of poor overall (HR=0.408; 95% confidence interval=0.247–0.674; P<0.001) and disease-free survival rates (HR=0.525; 95% confidence interval=0.216–0.584; P<0.001). GC cells showed significant reduction in cell migration and invasion upon depletion of MARCKS as noted through Matrigel invasion and cell wounding assays. Further analyses showed that silencing MARCKS impeded the epithelial-mesenchymal transition (EMT).

CONCLUSIONS: Our study indicates that elevated expression of MARCKS is significantly associated with metastatic capability of GC cells, and MARCKS overexpression can serve as a biomarker of GC poor prognosis.

Keywords: Epithelial-mesenchymal transition, Prognosis, Stomach Neoplasms, Aged, Aged, 80 and over, China, Disease-Free Survival, Immunohistochemistry, Intracellular Signaling Peptides and Proteins, Kaplan-Meier Estimate, Membrane Proteins, Middle Aged, Myristoylated Alanine-Rich C Kinase Substrate, Phosphorylation, Real-Time Polymerase Chain Reaction, transcriptional activation, transcriptome, Up-Regulation

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750