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

Sajjad Karim,Adeel Chaudhary,Mamdooh Gari,Zeenat Mirza,Mohammed Al-Qahtani,Adel Abuzenadah

doi:10.3390/ijms17020250

Sajjad Karim, Adeel Chaudhary + Show 4 more

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https://doi.org/10.3390/ijms17020250

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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.

Highlights

Regardless of its potential hazards, curative benefits of radiation have been reported in medicine, oncology in particular
The three prime categories of radiation therapy (RT) based on the differences relating to the position of the radiation sources are external beam RT where the radiation source is outside the body, sealed source RT employs sealed radioactive sources placed permanently or temporarily precisely in the area under treatment, and systemic unsealed source radioisotope therapy is given by oral ingestion of radioisotopes
We found that apoptosis signaling and cytotoxic T lymphocyte-mediated apoptosis of target cells pathways were strongly associated with RT

Summary

Introduction

Regardless of its potential hazards, curative benefits of radiation have been reported in medicine, oncology in particular. It is routinely used in cancer treatment prior to surgery to help shrink the tumor, as a palliative therapy to relieve pain, pressure and other neurologic or obstructive symptoms, and post-surgery to kill any remaining cancer cells and to prevent tumor recurrence or in synergy with chemotherapy [1]. Localized RT, using ionizing radiation, is the most common therapeutic option recommended for the treatment of ~60% of non-metastatic cancer patients [2,3,4]. Extra caution and personalized or tailored palliative radiotherapy administration is essential for patients in the end-stage of life with terminal cancer [9]

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