Comprehensive characterization of immune- and inflammation-associated biomarkers based on multi-omics integration in kidney renal clear cell carcinoma

J Transl Med. 2019 May 27;17(1):177. doi: 10.1186/s12967-019-1927-y.

Abstract

Background: Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cancer in adults, and it is responsible for approximately 90-95% of cases. Although extensive evidence has suggested that many immune- and inflammation-related genes could serve as effective biomarkers in KIRC, the potential associations among immune-, inflammation- and KIRC-related genes has not been sufficiently understood.

Methods: Here, we integrated multiple levels of data to construct an immune-, inflammation- or KIRC-directed neighbour network (IIKDN network) and a KIRC-related gene-directed network (KIRCD network).

Results: Our analysis suggested that immune- and inflammation-related genes in the network have special topological characteristics and expression patterns related to KIRC. We further identified five core clusters that showed a tighter network structure and stronger correlation of expression from the KIRCD network. Specifically, multiple-level molecular characteristics were systematically portrayed, including somatic mutation, copy-number variant and DNA methylation for the genes in five core clusters. We discovered that the genes showed strong correlation with respect to the expression and methylation levels in these five core clusters. These five core clusters could become special prognostic biomarkers for KIRC, and functional analysis showed that they were associated with activation of the immune and inflammation systems and cancer progression.

Conclusions: Our findings highlighted the novel role of the immune and inflammation genes in KIRC.

Keywords: DNA methylation; Immune; Inflammation; Kidney renal clear cell carcinoma; Multi-omics molecular; Network modules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / isolation & purification*
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Computational Biology / methods*
  • DNA Methylation
  • Databases, Genetic
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Genomics / methods
  • Humans
  • Immunity / genetics*
  • Inflammation / genetics*
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Metabolomics / methods
  • Phenomics / methods
  • Prognosis
  • Protein Interaction Maps
  • Systems Integration*

Substances

  • Biomarkers, Tumor