TNFSF9 Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Pancreatic Cancer

J Gastrointest Cancer. 2021 Mar;52(1):150-159. doi: 10.1007/s12029-020-00371-6.

Abstract

Background: TNFSF9 gene has been found to play an anti-tumor role and regulate the function of immune cells. However, the prognostic role of TNFSF9 in pancreatic cancer and its relationship with immune cell infiltration have not been studied.

Methods: We used Oncomine, UALCAN, and GEPIA databases to analyze the expression of TNFSF9 in pancreatic cancer. We used Kaplan-Meier plotters, GEPIA, and UALCAN to evaluate the effect of TNFSF9 on clinical prognosis. We further used TIMER to study the correlation between TNFSF9 and cancer immune infiltrate cells. In addition, we used GEPIA to analyze the correlation between TNFSF9 expression and gene markers of immune infiltrate cells.

Results: TNFSF9 mRNA expression level was remarkably increased in pancreatic cancer than that in normal tissues (both P < 0.05). In addition, high TNFSF9 expression was significantly related to poor overall survival (OS) and relapse-free survival (RFS) in pancreatic cancer (OS HR = 2.02, P = 0.0012; RFS HR = 2.63, P = 0.022). Moreover, high TNFSF9 expression in pancreatic cancer patients was associated with worse OS in stage 1 to 2 but not stage 3 and stage 4. Specifically, TNFSF9 expression and CD8+ T cell infiltration of pancreatic cancer was negatively correlated. TNFSF9 expression showed strong correlations with M1 macrophages in pancreatic cancer.

Conclusions: Our results suggest that TNFSF9 is associated with prognosis and CD8+ T cell infiltration levels in patients with pancreatic cancer. Further, TNFSF9 expression potentially contributes to the modulation of M1 polarization of macrophages. These findings indicate that TNFSF9 can be serves as a prognostic biomarker in determining the prognosis of pancreatic cancer and is associated with different types of phenotypes of immune cell infiltration.

Keywords: Lymphocytes; Macrophages; Pancreatic cancer; Prognosis; TNFSF9.

MeSH terms

  • 4-1BB Ligand / analysis
  • 4-1BB Ligand / metabolism*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / mortality*
  • Carcinoma, Pancreatic Ductal / therapy
  • Datasets as Topic
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Staging
  • Pancreas / immunology
  • Pancreas / pathology
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / therapy
  • Prognosis
  • Progression-Free Survival
  • RNA-Seq
  • Tumor Microenvironment / immunology
  • Tumor-Associated Macrophages / immunology

Substances

  • 4-1BB Ligand
  • Biomarkers, Tumor
  • TNFSF9 protein, human