Assessment of Radiation Induced Therapeutic Effect and Cytotoxicity in Cancer Patients Based on Transcriptomic Profiling

Abstract

Toxicity induced by radiation therapy is a curse for cancer patients undergoing treatment. It is imperative to understand and define an ideal condition where the positive effects notably outweigh the negative. We used a microarray meta-analysis approach to measure global gene-expression before and after radiation exposure. Bioinformatic tools were used for pathways, network, gene ontology and toxicity related studies. We found 429 differentially expressed genes at fold change >2 and p-value <0.05. The most significantly upregulated genes were synuclein alpha (SNCA), carbonic anhydrase I (CA1), X-linked Kx blood group (XK), glycophorin A and B (GYPA and GYPB), and hemogen (HEMGN), while downregulated ones were membrane-spanning 4-domains, subfamily A member 1 (MS4A1), immunoglobulin heavy constant mu (IGHM), chemokine (C-C motif) receptor 7 (CCR7), BTB and CNC homology 1 transcription factor 2 (BACH2), and B-cell CLL/lymphoma 11B (BCL11B). Pathway analysis revealed calcium-induced T lymphocyte apoptosis and the role of nuclear factor of activated T-cells (NFAT) in regulation of the immune response as the most inhibited pathways, while apoptosis signaling was significantly activated. Most of the normal biofunctions were significantly decreased while cell death and survival process were activated. Gene ontology enrichment analysis revealed the immune system process as the most overrepresented group under the biological process category. Toxicity function analysis identified liver, kidney and heart to be the most affected organs during and after radiation therapy. The identified biomarkers and alterations in molecular pathways induced by radiation therapy should be further investigated to reduce the cytotoxicity and development of fatigue.

Keywords

• radiation therapy
• toxicity
• microarray
• cancer
• pathway analysis