Lysyl-tRNA synthetase (KRS) expression in gastric carcinoma and tumor-associated inflammation

Ann Surg Oncol. 2014 Jun;21(6):2020-7. doi: 10.1245/s10434-014-3522-z. Epub 2014 Feb 21.

Abstract

Background: Lysyl-tRNA synthetase (KRS) is an aminoacyl-tRNA synthetase (ARS) that is essential for protein synthesis during ligation of specific amino acids to their cognate tRNAs. Aberrant expression of ARSs is associated with various human cancers.

Methods: Using immunohistochemical detection, the present study analyzed the clinical relevance of KRS expression in tumor cells and tumor-associated inflammatory cells (TAI) in 457 patients who underwent curative radical surgery and standard adjuvant therapy and who were observed on long-term follow-up.

Results: High expression of KRS in tumor cells (tumor-KRS(+)) was noted in 43.3 % (198 of 457) of cases. High expression of KRS in tumor-associated inflammatory cells (TAI-KRS(+)) including macrophages/monocytes, CD4-positive T cells, and/or neutrophils was observed in 37.2 % (170 of 457) of cases. Status of KRS in the tumor and TAI revealed an association with the known clinicopathological parameters for prognosis of gastric cancer. Tumor-KRS(+) status correlated to shorter overall survival, especially in stage III to IV cancers (P = 0.003), while TAI-KRS(+) status correlated significantly to longer overall survival in gastric cancer (P = 0.049). Cases with tumor-KRS(+) and TAI-KRS(-) status showed significantly reduced survival rates compared to those of other cases (P = 0.010), and status of tumor-KRS(+) and TAI-KRS(-) was revealed as an independently poor prognostic factor of overall survival (P = 0.001).

Conclusions: KRS-related inflammation can be identified in a subset of gastric cancer. This may be a possible mechanism of immune surveillance against tumor progression. In addition, expression status of KRS in tumor and TAI may be an independent prognostic marker for gastric cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / chemistry
  • Carcinoma / chemistry*
  • Carcinoma / pathology*
  • Carcinoma / therapy
  • Female
  • Humans
  • Inflammation / pathology*
  • Ki-67 Antigen / analysis
  • Lysine-tRNA Ligase / analysis*
  • Macrophages / chemistry
  • Male
  • Middle Aged
  • Monocytes / chemistry
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neutrophils / chemistry
  • Stomach Neoplasms / chemistry*
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / therapy
  • Survival Rate
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Ki-67 Antigen
  • Tumor Necrosis Factor-alpha
  • Lysine-tRNA Ligase