RNA-seq SSRs and small RNA-seq SSRs: new approaches in cancer biomarker discovery

Gene. 2015 Apr 10;560(1):34-43. doi: 10.1016/j.gene.2015.01.027. Epub 2015 Jan 30.

Abstract

The recent exponential increase in the number of next generation sequencing studies provides a new source of data for the discovery of functional genomics based markers. The RNA-seq and small RNA-seq provide a new source for the discovery of differentially expressed SSRs (simple sequence repeats) as biomarkers in various diseases. In the present study, for the first time, we applied RNA-seq SSR to find new biomarkers for pancreatic cancer (PC) diagnosis. Analysis of RNA-seq data revealed a significant alternation in the frequency of SSR motifs during cancer progression. In particular, RNA-seq SSR showed an increase in the frequencies of GCC/GGC and GCG/CGC motifs in PC samples compared to healthy pancreas. These findings were further confirmed using meta-analysis of EST-SSR data in 11 different cancers. Interestingly, the genes containing GCC/GGC and GCG/CGC motifs in their sequences were involved in many cancer-related biological processes, particularly regulation processes. The small RNA-seq data were also mined for the conserved patterns in SSR frequencies (sRNA-seq SSR) during cancer progression. Based on the results, we suggest the potential use of GCC/GGC and GCG/CGC motifs as biomarkers in PC. Based on the findings of this study, it seems that RNA-seq SSR and sRNA-seq SSR could open a new paradigm in the diagnostic and even therapeutic strategies for PC along the other types of cancers.

Keywords: Biomarker; EST–SSR; Leukemia; Next Generation Data Sequencing; Pancreatic cancer; RNA-seq; Small RNA-seq.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / isolation & purification
  • Expressed Sequence Tags
  • Female
  • Genetic Association Studies / methods*
  • HL-60 Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • K562 Cells
  • Male
  • Microsatellite Repeats*
  • Neoplasms / genetics*
  • RNA / genetics*
  • RNA, Small Untranslated / genetics
  • Sequence Analysis, RNA* / methods

Substances

  • Biomarkers, Tumor
  • RNA, Small Untranslated
  • RNA