Interaction of Epstein-Barr virus genes with human gastric carcinoma transcriptome

Dysregulation of expression of functional genes and pathways plays critical roles in the etiology and progression of hepatocellular carcinoma (HCC). Next generation‐based RNA sequencing (RNA‐seq) offers unparalleled power to comprehensively characterize HCC at the whole transcriptome level. In this study, 17 fresh‐frozen HCC samples with paired non‐neoplastic liver tissue from Caucasian patients undergoing liver resection or transplantation were used for RNA‐seq analysis. Pairwise differential expression analysis of the RNA‐seq data was performed to identify genes, pathways, and functional terms differentially regulated in HCC versus normal tissues. At a false discovery rate (FDR) of 0.10, 13% (n = 4335) of transcripts were up‐regulated and 19% (n = 6454) of transcripts were down‐regulated in HCC versus non‐neoplastic tissue. Eighty‐five Kyoto Encyclopedia of Genes and Genomes pathways were differentially regulated (FDR, <0.10), with almost all pathways (n = 83) being up‐regulated in HCC versus non‐neoplastic tissue. Among the top up‐regulated pathways was oxidative phosphorylation (hsa00190; FDR, 1.12E‐15), which was confirmed by Database for Annotation, Visualization, and Integrated Discovery (DAVID) gene set enrichment analysis. Consistent with potential oxidative stress due to activated oxidative phosphorylation, DNA damage‐related signals (e.g., the up‐regulated hsa03420 nucleotide excision repair [FDR, 1.14E‐04] and hsa03410 base excision repair [FDR, 2.71E‐04] pathways) were observed. Among down‐regulated genes (FDR, <0.10), functional terms related to cellular structures (e.g., cell membrane [FDR, 3.05E‐21] and cell junction [FDR, 2.41E‐07], were highly enriched, suggesting compromised formation of cellular structure in HCC at the transcriptome level. Interestingly, the olfactory transduction (hsa04740; FDR, 1.53E‐07) pathway was observed to be down‐regulated in HCC versus non‐neoplastic tissue, suggesting impaired liver chemosensory functions in HCC. Our findings suggest oxidative phosphorylation and the associated DNA damage may be the major driving pathologic feature in HCC.

Neoadjuvant therapy (NAT) is increasingly being used for pancreatic ductal adenocarcinoma (PDAC). This study investigates how NAT differentially impacts PDAC’s carcinoma cells and the tumor microenvironment (TME). Spatial transcriptomics was used to compare gene expression profiles in carcinoma cells and the TME of 23 NAT-treated versus 13 NAT-naïve PDACs. Findings were validated by single-nucleus RNA sequencing (snRNA-seq) analysis. NAT induces apoptosis and inhibits proliferation of carcinoma cells and coordinately upregulates multiple complement genes (C1R, C1S, C3, C4B and C7) within the TME. Higher TME complement expression following NAT is associated with increased immunomodulatory and neurotrophic cancer-associated fibroblasts (CAFs); more CD4⁺ T cells; reduced immune exhaustion gene expression, and improved overall survival. snRNA-seq analysis demonstrates C3 complement is mainly upregulated in CAFs. These findings suggest that local complement dynamics could serve as a novel biomarker for prognosis, evaluating treatment response, and guiding therapeutic strategies in NAT-treated PDAC patients.