Transcriptomic analyses revealed systemic alterations in gene expression in circulation and tumor microenvironment of colorectal cancer patients

Hibah Shaath, Salman M. Toor, Varun Sasidharan Nair, Eyad Elkord, Nehad M. Alajez

Research output: Contribution to journalArticle

Abstract

Colorectal cancer (CRC) is among the leading causes of cancer-related deaths worldwide, underscoring a need for better understanding of the disease and development of novel diagnostic biomarkers and therapeutic interventions. Herein, we performed transcriptome analyses on peripheral blood mononuclear cells (PBMCs), CRC tumor tissue and adjacent normal tissue from 10 CRC patients and PBMCs from 15 healthy controls. Up regulated transcripts from CRC PBMCs were associated with functions related to immune cell trafficking and cellular movement, while downregulated transcripts were enriched in cellular processes related to cell death. Most affected signaling networks were those involved in tumor necrosis factor (TNF) and interleukin signaling. The expression of selected immune-related genes from the RNA-Seq data were further validated using qRT-PCR. Transcriptome analysis of CRC tumors and ingenuity pathway analysis revealed enrichment in several functional categories related to cellular movement, cell growth and proliferation, DNA replication, recombination and repair, while functional categories related to cell death were suppressed. Upstream regulator analysis revealed activation of ERBB2 and FOXM1 networks. Interestingly, there were 18 common upregulated and 36 common downregulated genes when comparing PBMCs and tumor tissue, suggesting transcriptomic changes in the tumor microenvironment could be reflected, in part, in the periphery with potential utilization as disease biomarkers.

Original languageEnglish
Article number1994
JournalCancers
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2019

Fingerprint

Tumor Microenvironment
Colorectal Neoplasms
Gene Expression
Blood Cells
Gene Expression Profiling
Cell Death
Down-Regulation
Biomarkers
Activation Analysis
Recombinational DNA Repair
Interleukins
DNA Replication
DNA Repair
Genes
Neoplasms
Tumor Necrosis Factor-alpha
Cell Proliferation
RNA
Polymerase Chain Reaction
Growth

Keywords

  • Colorectal cancer (CRC)
  • Differential expression
  • Disease biomarkers
  • Immune regulation
  • Inflammation
  • Peripheral blood mononuclear cell (PBMC)
  • Transcriptome sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Transcriptomic analyses revealed systemic alterations in gene expression in circulation and tumor microenvironment of colorectal cancer patients. / Shaath, Hibah; Toor, Salman M.; Nair, Varun Sasidharan; Elkord, Eyad; Alajez, Nehad M.

In: Cancers, Vol. 11, No. 12, 1994, 12.2019.

Research output: Contribution to journalArticle

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