Stool Bacteriomic Profiling in Patients with Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitors

Clin Cancer Res. 2015 Dec 1;21(23):5286-93. doi: 10.1158/1078-0432.CCR-15-0724. Epub 2015 Jul 7.

Abstract

Purpose: Diarrhea occurs in approximately half of patients with metastatic renal cell carcinoma (mRCC) receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI). We evaluated the relationship between VEGF-TKI-related diarrhea and stool microbiota.

Experimental design: Stool samples were collected from 20 mRCC patients receiving VEGF-TKIs. 16S rRNA sequencing was used to characterize the stool bacteriomic profiling of patients. Assay validation with Salmonella typhimurium spike-in experiments suggested greatest speciation with use of the V5 region.

Results: Higher levels of Bacteroides spp. and lower levels of Prevotella spp. were found in patients with diarrhea. In addition, patients receiving VEGF-TKIs with mRCC appeared to have less relative abundance of Bifidobacterium spp. as compared with previous reports based on healthy subjects.

Conclusions: We have thus demonstrated interplay between microbiota and VEGF-TKI-induced diarrhea. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in VEGF-TKI-related diarrhea.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Bacteria / classification*
  • Bacteria / genetics*
  • Biodiversity
  • Carcinoma, Renal Cell / complications*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / pathology
  • Cluster Analysis
  • Diarrhea / etiology*
  • Diarrhea / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Kidney Neoplasms / complications*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / pathology
  • Male
  • Metagenome
  • Metagenomics / methods
  • Middle Aged
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • RNA, Ribosomal, 16S / genetics
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • RNA, Ribosomal, 16S
  • Vascular Endothelial Growth Factor A