Prognostic Significances of NEDD-9 and FOXL-1 Expression in Intestinal Type Gastric Carcinoma: an Immunohistochemical Study

J Gastrointest Cancer. 2021 Jun;52(2):728-737. doi: 10.1007/s12029-020-00471-3.

Abstract

Background: Gastric cancer (GC) is mostly diagnosed at advanced stage, so prognosis is poor. Therefore, it is necessary to understand the molecular mechanism of GC development to design new targeted treatment to improve the prognosis of gastric cancer patients.

Aim of the work: To assess the prognostic value of NEDD-9 and FOXL-1 expression in intestinal type gastric cancer patients, as well as their relationship to clinicopathologic features of the disease and patients outcome.

Patients and methods: This is a retrospective study; we included 50 sections from formalin-fixed, paraffin-embedded tissue samples which included intestinal type GC and adjacent non-neoplastic gastric mucosa in the same block that were subjected to immunohistochemistry with anti-NEDD-9 and anti-FOXL-1 antibody. Patients were retrospectively followed up for about 5 years for assessment of tumor progression and survival in relation to marker expression.

Results: High NEDD-9 and low FOXL-1 expression were found in intestinal type GC more than adjacent non-neoplastic mucosa (p < 0.001). NEDD-9 high expression and FOXL-1 low expression were associated with presence of helicobacter pylori gastritis (p = 0.010, 0.049), high grade (p = 0.007, 0.004), high stage (p < 0.001), presence of distant metastases (p = 0.029, 0.021), poor DFS (p = 0.003), and OS rates (< 0.001).

Conclusion: NEDD-9 overexpression and FOXL-1 deficiency in intestinal type GC can help in prediction of tumor prognosis and it can guide the selection of patients for future therapies in gastric carcinoma.

Keywords: FOXL-1; Immunohistochemistry; Intestinal type GC; NEDD-9; Prognosis.

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Carcinoma / diagnosis
  • Carcinoma / mortality*
  • Carcinoma / pathology
  • Carcinoma / surgery
  • Disease Progression
  • Disease-Free Survival
  • Follow-Up Studies
  • Forkhead Transcription Factors / analysis*
  • Forkhead Transcription Factors / metabolism
  • Gastrectomy
  • Gastric Mucosa / pathology
  • Gastric Mucosa / surgery
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • FOXL1 protein, human
  • Forkhead Transcription Factors
  • NEDD9 protein, human