Prognostic Biomarkers in Early-stage Gastric Adenocarcinoma Treated With Adjuvant Chemoradiotherapy

Cancer Genomics Proteomics. 2020 May-Jun;17(3):277-290. doi: 10.21873/cgp.20188.

Abstract

Background/aim: Early-stage gastric cancer has a high risk of recurrence, despite trimodality therapy with surgery, chemotherapy and radiation. To improve patient selection for adjuvant chemoradiotherapy, we evaluated the prognostic significance of immunohistochemical and genetic biomarkers in patients with resected gastric adenocarcinoma.

Patients and methods: Tumors from 119 patients were subjected to immunohistochemistry for 12 protein biomarkers, as well as next-generation sequencing. Clinical and biomarker data were available for 91 patients.

Results: EBV-positive tumors and tumors with mutations had higher intratumoral CD8 tumor-infiltrating lymphocyte density (p=0.009 and p=0.017, respectively). PIK3CA mutations were correlated with VEGFA overexpression (p=0.042), while KRAS mutations and HER2 expression were mutually exclusive (p=0.036). PTEN expression univariately confirmed longer overall survival (HR=0.27; p=0.046), while there was a trend between the presence of KRAS mutations and inferior disease-free and overall survival.

Conclusion: PTEN protein expression and KRAS mutations may predict disease outcome in early-stage gastric cancer. These results need to be further validated in larger cohorts.

Keywords: Biomarkers; chemoradiotherapy; gastric cancer.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Chemoradiotherapy, Adjuvant
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Retrospective Studies
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Proto-Oncogene Proteins p21(ras)