Low expression of SOCS-1 and SOCS-3 is a poor prognostic indicator for gastric cancer patients

J Cancer Res Clin Oncol. 2015 Mar;141(3):443-52. doi: 10.1007/s00432-014-1838-5. Epub 2014 Sep 28.

Abstract

Background and objectives: Inflammation plays an important role in gastric cancer (GC) development and progression. Suppressor of cytokine signaling (SOCS)-1 and SOCS-3 negatively regulate proinflammatory cytokine signaling; however, their prognostic significance in GC remains unknown. We evaluated the clinicopathological correlation and prognostic significance of SOCS-1 and SOCS-3 in GC.

Methods: SOCS-1 and SOCS-3 mRNA levels were analyzed in 80 paired gastric tumor and adjacent normal mucosal tissues using a microarray dataset from the Gene Expression Omnibus. Univariate and multivariate analyses were performed to investigate the prognostic impact of SOCS-1 and SOCS-3 immunohistochemical expression on overall survival (OS) and relapse-free survival (RFS) in 186 consecutive GC patients who underwent curative surgery.

Results: SOCS-1 and SOCS-3 mRNA expression levels were lower in gastric tumor tissues than in matched normal mucosa. OS and RFS were significantly longer in the high SOCS-1 and SOCS-3 expression groups than in their corresponding low expression groups (p < 0.05). High simultaneous SOCS-1 and SOCS-3 expression were associated with longer OS compared with low simultaneous SOCS-1 and SOCS-3 expression (68.8 vs. 22.2 months; p < 0.001). SOCS-1 [hazards ratio (HR) 0.54, 95 % confidence interval (CI) 0.33-0.87, p = 0.011] and SOCS-3 (HR 0.46, 95 % CI 0.26-0.80, p = 0.006) were independent prognostic factors for OS. Only SOCS-1 (HR 0.20, 95 % CI 0.11-0.38, p = 0.006) was an independent prognostic factor for RFS.

Conclusion: Low SOCS-1 and SOCS-3 expression are poor prognostic indicators in GC. GC patients with low SOCS-1 and SOCS-3 expression need close follow-up.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Signet Ring Cell / metabolism
  • Carcinoma, Signet Ring Cell / mortality
  • Carcinoma, Signet Ring Cell / secondary
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Gastric Mucosa / metabolism*
  • Gene Expression Profiling
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach / pathology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • SOCS1 protein, human
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins