Identification of Prognostic and Therapeutic Biomarkers among FAM83 Family Members for Pancreatic Ductal Adenocarcinoma

Dis Markers. 2021 Mar 1:2021:6682697. doi: 10.1155/2021/6682697. eCollection 2021.

Abstract

Family with sequence similarity 83 (FAM83) members were shown recently to have oncogenic effect in a variety of cancer types, but the biological roles and prognostic value of FAM83 family in pancreatic ductal adenocarcinoma remain unknown. In the current study, the clinical significance and molecular function of the FAM83 family were assessed by multiple bioinformatics analysis. Besides, potential associations between differentially expressed genes (DEGs) of FAM83 family and antitumor immunity were evaluated using TIMER and TISIDB analyses. As the results show, FAM83A, FAM83D, FAM83E, and FAM83H were significantly upregulated in PDAC and were identified as DEGs. Higher expression of FAM83A, FAM83B, FAM83D, FAM83E, and FAM83H were associated with advanced tumor stage or worse patient prognosis. Importantly, the overexpression of DEGs was found to be significantly correlated with activated KRAS and loss of SMAD4, which are important drivers for PDAC. Further, FAM83A, FAM83D, and FAM83H were associated with CD8+ T cell, Gamma Delta T cell, and CD4+ T cell infiltration in PDAC and FAM83H was found closely correlated with some immunomodulators including immunoinhibitors, immunostimulators, and MHC molecules. In conclusion, FAM83A, FAM83D, FAM83E, and FAM83H have significant prognostic value in PDAC and they may play important roles in regulating tumor progression and the immune cell infiltration.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Movement
  • Humans
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Proteins / genetics*
  • Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Smad4 Protein / genetics
  • Smad4 Protein / metabolism
  • T-Lymphocytes / physiology
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • FAM83A protein, human
  • FAM83D protein, human
  • FAM83H protein, human
  • KRAS protein, human
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Proto-Oncogene Proteins p21(ras)