Prognostic value of mixed lineage kinase domain-like protein expression in the survival of patients with gastric caner

Tumour Biol. 2016 Oct;37(10):13679-13685. doi: 10.1007/s13277-016-5229-1. Epub 2016 Jul 29.

Abstract

The aim of this study was to detect mixed lineage kinase domain-like protein (MLKL) expression in gastric cancer (GC) and to analyze its association with the prognosis of GC patients. Immunohistochemical staining, Western blotting, and quantitative reverse-transcriptase polymerase chain reaction were performed to detect MLKL tissue expression in 117 GC patients. Clinicopathological characteristics and survival data were retrospectively analyzed to discover the clinical importance of MLKL expression. The chi-square test was used to analyze the relationship between MLKL expression and the clinicopathological characteristics. Survival curves were plotted by using the Kaplan-Meier method and compared using the log-rank test. Survival data were evaluated using univariate and multivariate Cox regression analyses. The expression of MLKL mRNA was significantly higher in adjacent normal samples than in the tumor tissues (P = 0.003). Clinicopathological analysis showed that MLKL expression was significantly correlated with age (P = 0.013), histologic type (P = 0.049), differentiation grade (P < 0.001), depth of invasion (P = 0.022), and lymph node metastasis (P = 0.003). Low MLKL expression was significantly associated with decreased overall survival (median 29 months vs. 56 months, P < 0.001). Multivariate analysis suggested that MLKL expression might be an independent prognostic indicator (HR = 0.645, 95 % CI, 0.446-1.165, P = 0.002) for GC patients. In conclusion, our findings provide evidence that MLKL might serve as a candidate tumor suppressor and a potential prognostic biomarker for GC.

Keywords: Gastric cancer; MLKL; Overall survival; Prognosis.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • MLKL protein, human
  • Protein Kinases