Interleukin ۸ as a Candidate Biomarkerfor Unfavorable Prognosis in Esophageal Squamous CellCarcinoma

Background: Esophageal squamous cell carcinoma (ESCC) isa highly lethal malignancy arising from the cells lining the esophagus.Identifying key genes involved in the transition fromthe paratumor stage to tumor progression is crucial due to thepredicted increase in incidence.Materials and Methods: To obtain ۲۸ tumor tissue and ۲۸paratumor tissue samples of ESCC, normalized data fromGSE۱۶۱۵۳۳ were downloaded using GEOquery. Differentialexpression analysis was performed using a threshold of andadj P-value < ۰.۰۵ to identify differentially expressed genes(DEGs). Subsequently, the PPI network (PPIN) was constructedusing the STRING database and analyzed with the cytoHubbaapp in Cytoscape. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology (GO) enrichment analysis ofDEGs were conducted using the Enrichr database and cluster-Profiler package in R, respectively.Results: A total of ۱۳۹ DEGs were identified between thetumor and paratumor samples, with ۴۵ up-regulated and ۹۴down-regulated genes. Analysis of KEGG pathways revealedsignificant enrichment in the interleukin ۱۷ (IL-۱۷) signalingpathway. Furthermore, the GO analysis identified significantenrichment of external encapsulating structure organization(GO:۰۰۴۵۲۲۹), serine-type peptidase activity (GO:۰۰۰۸۲۳۶),and collagen-containing extracellular matrix (GO:۰۰۶۲۰۲۳) inbiological processes, molecular functions, and cellular components,respectively. IL-۸ or C-X-C motif chemokine ligand ۸(CXCL۸), matrix metallopeptidase ۹ (MMP۹), matrix metallopeptidase۳ (MMP۳), periostin (POSTN), and secreted phosphoprotein۱ (SPP۱) were hub genes among the DEGs in PPINbased on their degree score (top ۵). Analysis of survival plotsrevealed only IL-۸ had a significant impact on survival rates(P= ۰.۰۱۸), indicating that individuals with up-regulated IL-۸may be at higher risk.Conclusion: The present study identified ۱۳۹ DEGs in ESCCwith IL-۸, MMP۹, MMP۳, POSTN, and SPP۱ as hub genes.IL-۸ significantly impacted poor prognosis for patients, highlightingpotential targets for early identification and multimodaltreatments in ESCC patients.

کلیدواژه ها:

Esophageal cancer ، Bioinformatics ، Interleukin ۸ ، Cancer prognosis