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Comparative transcriptome characterization of paired primary gastric cancer and ovarian metastasis

ABSTRACT: To understand the molecular mechanism underlying ovarian metastasis of gastric cancer, we performed RNA-seq of paired primary tumor, normal mucosa and ovarian metastasis of four GC patients by the Illumina sequencing platform with 150-bp paired-end, followed by functional enrichment analyses of differentially expressed genes between three sample sets. A total number of 15,493 protein-coding genes were detected, the majority of which were the annotated human reference genes. Using a threshold of fold change >2 and adjusted P value <0.05, a total number of 3023 differentially expressed genes were detected between different sets of samples. Among them, 479 and 609 protein-coding genes were up- and down-regulated in ovarian metastases over primary tumors, respectively. Functional enrichment analyses revealed the significant enrichment of immune system, tumor microenvironment, metabolism and sex hormone-related pathways in the ovarian metastasis of gastric cancer. In conclusion, comparative transcriptome characterization of paired primary and ovarian metastatic tumor profiled the genome-wide molecular expression and unveiled functionally enriched pathways underlying this specific type of distant metastasis in GC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE191139 | GEO | 2021/12/20

REPOSITORIES: GEO

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Project description:The better prognosis of patients with Epstein-Barr virus-positive gastric carcinoma than those with EBV-negative GC is correlated with the degree of recruitment of inflammatory tumor infiltrating cells (TIL) to the vicinity of tumor cells. We hypothesized that the better prognosis would associate with less genetic or epigenetic alterations in EBV(+)GC, or EBV infection should deregulate immune modulator proteins, of which secretion recruit TIL. Therefore we performed mRNA expression profilings in EBV(-)GC and EBV(+)GC, each of which was pair wise compared with their normal control. We found that EBV(+)GC had much more molecular homogeneity with focused alterations in immune modulator genes; The Pearson correlation matrix analyses demonstrated that EBV(+)GC tumor showed remarkably high tumor homogeneity. While EBV(-)GC had considerable number genes that are differentially expressed genes from their normal counterparts, EBV(+)GC showed only a handful, almost 20 fold less number of DEG than EBV(-)GC under the same p value cutoff (p<0.001). Gene ontology and pathway analyses showed that while pathways of cation homeostasis, digestion and ion transport were commonly deregulated in both GC types, genes for chromatin assembly, prostaglandin receptor activity, pattern specification process are selectively deregulated in EBV(-)GC tumors. In contrast, pathways or genes for cytokine activity, immune response and lipoprotein particle clearance are selectively deregulated in EBV(+)GC tumors. These results demonstrate that EBV(+)GC inherently evolves to high homogeneity with fewer changes in gene expression and these secret immune modulatory chemokines could recruit reactive immune cells to EBV(+)GC, leading to favorable microenvironment for cancer suppression. All patients underwent the surgery for advanced gastric carcinoma (GC) except one patient with early GC. The EBV-presence in the GC was verified by in situ EBV-encoded small RNA (ERER) staining.. The 14 paired EBV(-)GC patients and 12 paired EBV(+)GC patients were selected for this study. Tumor tissue (T)and normal tissues (N) from distant sites from tumor areas were dissected, frozen at -80C and were subjected to RNA purification, mRNA array profiling analyses.

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Comparative transcriptome characterization of paired primary gastric cancer and ovarian metastasis

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