Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma

Cancer Immunol Immunother. 2022 Feb;71(2):491-504. doi: 10.1007/s00262-021-03012-4. Epub 2021 Jul 13.

Abstract

Objective: To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD).

Methods: The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized.

Results: High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer.

Conclusions: The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.

Keywords: Immune; KRAS G12V; Neoantigen; Pancreatic adenocarcinoma.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Aged
  • Antigens, Neoplasm / immunology*
  • Biomarkers, Tumor / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pancreatectomy / mortality*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Retrospective Studies
  • Survival Rate
  • Transcriptome
  • Tumor Microenvironment*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)