Synthetic messenger RNA vaccines and transcriptomic dysregulation: Evidence from new-onset adverse events and cancers post-vaccination

Table 3 Gene set enrichment results for group 2 categorized by molecular pathway

Molecular pathways	MSigDB standard name	Normalized Enrichment Score	False discovery rate
Transcriptomic instability and translational stress	REACTOME_SIRT1_NEGATIVELY_REGULATES_RRNA_EXPRESSION	3.08	> 0.001
	REACTOME_RNA_POLYMERASE_I_PROMOTER_ESCAPE	2.61	> 0.001
	REACTOME_TRANSCRIPTIONAL_REGULATION_BY_SMALL_RNAS	2.63	> 0.001
	REACTOME_B_WICH_COMPLEX_POSITIVELY_REGULATES_RRNA_EXPRESSION	2.60	> 0.001
	REACTOME_POSITIVE_EPIGENETIC_REGULATION_OF_RRNA_EXPRESSION	2.54	> 0.001
	REACTOME_RRNA_MODIFICATION_IN_THE_NUCLEUS_AND_CYTOSOL	2.03	0.027
Systemic inflammatory and immune response	KEGG_MEDICUS_REFERENCE_TYPE_I_INTERFERON_TO_JAK_STAT_SIGNALING_PATHWAY	2.64	> 0.001
	KEGG_MEDICUS_PATHOGEN_HIV_TAT_TO_TLR2_4_NFKB_SIGNALING_PATHWAY	2.73	> 0.001
	KEGG_MEDICUS_REFERENCE_TYPE_I_IFN_SIGNALING_PATHWAY	2.64	> 0.001
	KEGG_MEDICUS_REFERENCE_RIG_I_NFKB_SIGNALING_PATHWAY	2.54	> 0.001
	KEGG_MEDICUS_REFERENCE_TLR3_IRF7_SIGNALING_PATHWAY	2.46	> 0.001
	KEGG_MEDICUS_REFERENCE_TLR7_8_9_IRF5_SIGNALING_PATHWAY	2.29	> 0.001
	KEGG_MEDICUS_REFERENCE_TLR7_9_IRF7_SIGNALING_PATHWAY	2.27	> 0.001
	KEGG_MEDICUS_REFERENCE_MDA5_IRF7_3_SIGNALING_PATHWAY	2.0	0.006
	KEGG_MEDICUS_REFERENCE_IFN_RIPK1_3_SIGNALING_PATHWAY	2.0	0.006
	KEGG_MEDICUS_REFERENCE_RIG_I_IRF7_3_SIGNALING_PATHWAY	2.0	0.007
	GAVISH_3CA_METAPROGRAM_CD8_T_CELLS_CHROMATIN	1.78	0.068
Endothelium dysfunction	GOBP_NEGATIVE_REGULATION_OF_ENDOTHELIAL_CELL_PROLIFERATION	-1.98	0.0017
	GOBP_NEGATIVE_REGULATION_OF_COAGULATION	-1.98	0.0017
Proliferative signaling and suppressed tumor control	REACTOME_ASSEMBLY_OF_THE_ORC_COMPLEX_AT_THE_ORIGIN_OF_REPLICATION	2.93	> 0.001
Genomic instability and epigenetic shift	REACTOME_DNA_METHYLATION	3.18	> 0.001
	REACTOME_CONDENSATION_OF_PROPHASE_CHROMOSOMES	2.93	> 0.001
	KEGG_MEDICUS_REFERENCE_CGAS_STING_SIGNALING_PATHWAY	2.43	> 0.001
	GAVISH_3CA_MALIGNANT_METAPROGRAM_4_CHROMATIN	1.91	0.05
	GOBP_NUCLEOSOME_ORGANIZATION	2.33	0.01

The Table 3 displays the top gene sets within each category, along with their corresponding MSigDB identifiers, Normalized Enrichment Score (NES), and false discovery rate (FDR) q value. Positive NES values indicate upregulation, while negative NES values indicate downregulation of the gene sets in vaccinated samples relative to controls. Gene sets were selected based on biological relevance and NES >|15| with FDR q < 0.25. Group 2 includes patients with new-onset cancers diagnosed shortly after messenger RNA coronavirus disease 2019 vaccination (n = 7), compared with normal controls (n = 803 unvaccinated individuals from the GTEx dataset).