Transcriptome Signature of Immune Cells Post Reovirus Treatment in KRAS Mutated Colorectal Cancer
| Autor: | Sanjay Goel, Radhashree Maitra, Avishai Samouha, Elisha Fogel |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
VEGFB
Colorectal cancer CASP8 RTN4 Biology reovirus medicine.disease medicine.disease_cause Peripheral blood mononuclear cell Fold change CRC Oncolytic virus Transcriptome CHORDC1 Oncology Cancer Management and Research Gene expression KRAS Cancer research SOS1 medicine transcriptome Original Research |
| Zdroj: | Cancer Management and Research |
| ISSN: | 1179-1322 |
| DOI: | 10.2147/cmar.s324203 |
| Popis: | Elisha J Fogel,1 Avishai Samouha,1 Sanjay Goel,2 Radhashree Maitra1,2 1Department of Biology, Yeshiva University, New York, NY, 10033, USA; 2Albert Einstein College of Medicine at Montefiore Medical Center, Bronx, NY, 10461, USACorrespondence: Radhashree MaitraDepartment of Biology, Yeshiva University, 500 W 185th Street, New York, NY, 10033, USATel +1 718-801-1359Email Radhashree.maitra@yu.eduPurpose: Reovirus propagates with high efficiency in KRAS mutated colorectal cancer (CRC). About 45â 50% of CRC patients possess a KRAS mutation. Oncolytic reovirus treatment in combination with chemotherapy was tested in patients possessing KRAS mutated metastatic CRC. This study evaluates the biological responses to reovirus treatment by determining the gene expression patterns in RAS-related signaling pathways.Methods: Reovirus was administered as a 60-min intravenous infusion for 5 consecutive days every 28âdays, at a tissue culture infective dose (TCID50) of 3Ã 1010. Peripheral blood mononuclear cells (PBMCs) were isolated from whole-blood pre- and post-reovirus administration at 48 hr, day-8, and day-15. Clariom_D_Human_Assay was used to determine the expression of vital genes compared to pre-reovirus treatment by RNA sequencing. Using exported sample signals, ÎÎCt method was used to analyze the fold changes of genes within seven gene pathways. Significance was calculated by students-two-tail-t-test. Hierarchical clustering dendrogram was constructed by calculating Pearsonâs correlation coefficients.Results: As compared to the control, SOS1[48 hr; 2.49X], RRAS [48 hr; 2.24X], PIK3CB [D8, D15; 2.27X, 3.16X], MIR 16â 2 [D15; 1.70X], CHORDC1 [48 hr, D15; 1.89X, 4.54X], RTN4 [48 hr; 4.66X], FAM96A [48 hr; 4.54X], NFKB [D8, D15; 19.0X, 1.42X], CASP8 [D8, D15; 2.11X, 1.77X], and CASP9 [D8; 1.45X] are upregulated post-reovirus. NOS3 [D15; 0.61X], SYNE1 [D8, D15; 0.78X, 0.71X], ANGPT1 [D8; 0.62X], VEGFB [48 hr, D8, D15; 0.44X, 0.28X, 0.28X], JUN [D15; 0.69X], and IGF2 [D8; 0.73X] are downregulated post-reovirus. Fold change values were significant [p< 0.05].Conclusion: This study highlights reovirus as a novel treatment option for KRAS mutated CRC and showcases its effect on the expression of crucial genes.Keywords: transcriptome, reovirus, CRC, KRAS, CASP8, CHORDC1, RTN4, VEGFB |
| Databáze: | OpenAIRE |
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