Abstract 347P
Background
Pancreatic cancer is the 12th most common cancer worldwide, with pancreatic adenocarcinoma (PAAD) making up about 90% of cases. PAAD is notorious for its poor 5-year survival rate of 10%, with over half of the diagnoses being metastatic. The prognostic role of ENHO in PAAD is not fully understood, necessitating a bioinformatic exploration.
Methods
We extracted Differentially Expressed Genes (DEGs) associated with ENHO expression from the TCGA database using the R package DESeq2. ENHO expression levels and co-expressed genes were analyzed via cBioportal. Gene set enrichment analysis (GSEA) was conducted via TCGAbiolinks, with further enrichment performed on enrichr. Immune infiltration was examined using TIMER2.0. Survival analysis used TCGA data, employing the "survminer" and "survival" R packages.
Results
Our analysis indicated that ENHO was downregulated in advanced stages of PAAD (F=7.41, p<0.001). Notably, higher levels of ENHO expression were associated with a protective effect on overall survival (OS) (HR:0.44, 95%CI: 0.339 – 0.541, p=0.0021). RNA-seq analysis identified 3962 DEGs, with 2957 upregulated and 1006 downregulated between high and low ENHO expression groups. GSEA of upregulated genes in the high ENHO group highlighted pathways related to pancreatic beta-cell regulation, insulin secretion, G-protein coupled receptor activity, insulinomas, and the complement cascade. Conversely, downregulated genes were involved in Syndecan-1 pathways, epithelial to mesenchymal transition, extracellular matrix organization, activation of metalloproteinases, integrins in angiogenesis, and cancer metastasis. GSEA on co-expressed genes showed associations with glucagon signaling, regulation of insulin secretion, and G-protein signaling pathways. The immune infiltration assay revealed associations of high ENHO expression with increased infiltration of CD8 T cells, CD4 T cells, M2 Macrophages, and plasma B cells.
Conclusions
Our findings highlight that ENHO is linked to changes in immune infiltration, angiogenesis, regulation of the extracellular matrix, and modulation of specific carcinogenic processes. The modulation of these processes by ENHO suggests improved OS and prognosis for PAAD patients, but validation through an external cohort is still needed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.