Extracting tumor tissue immune status from expression profiles: correlating renal cancer prognosis with tumor-associated immunome

Oncotarget. 2015 Oct 20;6(32):33191-205. doi: 10.18632/oncotarget.5052.

Abstract

Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative for prognosis prediction. However, evaluating the expression of immune-associated genes within cancer biopsy is subject to significant inconsistencies related to the sampling methodology. Here, we present immFocus, a method for extracting immune signals from total RNA sequencing of tumor biopsies, intended for immunity depiction and prognosis evaluation. It is based on reducing the variation which biopsy preparation adds to the apparent expression levels of immune genes. We employed immFocus to normalize gene expression with an immune index using data obtained from renal clear cell carcinoma biopsies. Genes that became less variable due to normalization were found to be preferentially immune-related. Moreover, immune-related genes tended to become more prognostic due to the normalization. These results demonstrate, for the first time, that whole transcriptome sequencing can be used for interrogation of a cancer immunome and for advancing immune-based prognosis.

Keywords: RNAseq; TCGA; cancer microenvironment; immunome; precision cancer medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / mortality
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic* / immunology
  • Humans
  • Immune System / metabolism*
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / mortality
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Survival Analysis
  • Transcriptome / immunology*

Substances

  • Leukocyte Common Antigens