SLITRK3 expression correlation to gastrointestinal stromal tumor risk rating and prognosis

World J Gastroenterol. 2015 Jul 21;21(27):8398-407. doi: 10.3748/wjg.v21.i27.8398.

Abstract

Aim: To assess the influence of SLIT and NTRK-like family member 3 (SLITRK3) on the prognosis of gastrointestinal stromal tumor (GIST) and determine whether SLITRK3 can help improve current risk stratification systems.

Methods: We hypothesized that SLITRK3 could be used as a prognostic molecular biomarker for GIST. 35 fresh tumor samples and 417 paraffin-embedded specimens from GIST patients were utilized. SLITRK3 mRNA expression in GIST tumor tissue was detected by real-time polymerase chain reaction, and SLITRK3 protein levels were estimated by immunohistochemistry. The correlation of SLITRK3 expression with various tumor clinicopathological characteristics and follow-up data were analyzed.

Results: GIST tumors had high expression of SLITRK3 compared with adjacent normal tissues and the expression level gradually increased with risk grade. SLITRK3 protein expression was closely associated with gastrointestinal bleeding, tumor site, tumor size, mitotic index, and National Institutes of Health (NIH) classification. Survival analysis showed that SLITRK3 expression was closely correlated with overall survival and disease-free survival of GIST patients. Multivariate analysis also identified SLITRK3 expression, mitotic index, and NIH stage as significant risk factors of GIST recurrence.

Conclusion: SLITRK3 expression is a highly significant predictor of GIST recurrence and metastasis. Combinations of SLITRK3 and NIH stage have strong predictive and prognostic value, and are feasible markers for clinical practice in gastrointestinal stromal tumor.

Keywords: Biomarkers; Gastrointestinal stromal tumor; Non-epithelial tumors; Risk stratification; SLITRK3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gastrointestinal Neoplasms / chemistry*
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / mortality
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Neoplasms / therapy
  • Gastrointestinal Stromal Tumors / chemistry*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / mortality
  • Gastrointestinal Stromal Tumors / secondary
  • Gastrointestinal Stromal Tumors / therapy
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / analysis*
  • Membrane Proteins / genetics
  • Middle Aged
  • Mitotic Index
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Recurrence, Local
  • Nerve Tissue Proteins / analysis*
  • Nerve Tissue Proteins / genetics
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Tumor Burden
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • SLITRK3 protein, human