The genetic landscape of pancreatic head ductal adenocarcinoma in China and prognosis stratification

BMC Cancer. 2022 Feb 18;22(1):186. doi: 10.1186/s12885-022-09279-9.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is the major subtype of pancreatic cancer and head PDACs show distinct characteristics from body/tail PDACs. With limited studies based on Asian population, the mutational landscape of Asian PDAC remains unclear.

Methods: One hundred fifty-one Chinese patients with head PDAC were selected and underwent targeted 425-gene sequencing. Genomic alterations, tumor mutational burden, and microsatellite instability were analyzed and compared with a TCGA cohort.

Results: The genomic landscape of Chinese and Western head PDAC had identical frequently-mutated genes including KRAS, TP53, SMAD4, and CDKN2A. KRAS hotspot in both cohorts was codon 12 but Chinese PDACs containing more G12V but fewer G12R variants. Potentially pathogenic fusions, CHD2-BRAF and KANK1-MET were identified in two KRAS wild-type patients. Serum cancer antigens CA125 and CA19-9 were positively associated with SMAD4 alterations while high CEA was enriched in wild-type CDKN2A subgroup. The probability of vascular invasion was lower in patients with RNF43 alterations. The nomogram developed including histology grade, the mutation status of SMAD4, TGFBR2, and PREX2 could calculate the risk score of prognoses validated by Chinese and TCGA cohort.

Conclusions: Chinese head PDAC contained more KRAS G12V mutation than Western population. The well-performed nomogram may improve post-operation care in real-world practice.

Keywords: Genomic landscape; NGS; Pancreatic cancer; Prognosis prediction.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Biomarkers, Tumor / genetics
  • Carcinoma, Pancreatic Ductal / ethnology
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / mortality
  • China
  • Codon
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Female
  • Genomics
  • Humans
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mutation
  • Pancreatic Neoplasms / ethnology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Smad4 Protein / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Codon
  • Cyclin-Dependent Kinase Inhibitor p16
  • KRAS protein, human
  • SMAD4 protein, human
  • Smad4 Protein
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins p21(ras)