Novel insight into pancreatic adenocarcinoma pathogenesis using liquid association analysis

Abstract

Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy associated with a poor prognosis. High-throughput disease-related-gene expression data provide valuable information on gene interaction, which consequently lead to deeper insight about pathogenesis. The co-expression analysis is a common approach that is used to investigate gene interaction. However, such an approach solely is inadequate to reveal the complexity of the gene interaction. The three-way interaction model is known as a novel approach applied to decode the complex relationship between genes. Methods In the current study, the liquid association method was used to capture the statistically significant triplets involved in the PDAC pathogenesis. Subsequently, gene set enrichment and gene regulatory network analyses were performed to trace the biological relevance of the statistically significant triplets. Results The results of the current study suggest that “response to estradiol” and “Regulation of T-cell proliferation” are two critical biological processes that may be associated with the PDAC pathogenesis. Additionally, we introduced six switch genes, namely Lamc2, Klk1, Nqo1, Aox1, Tspan1, and Cxcl12, which might be involved in PDAC triggering. Conclusion In the current study, for the first time, the critical genes and pathways involved in the PDAC pathogenesis were investigated using the three-way interaction approach. As a result, two critical biological processes, as well as six potential biomarkers, were suggested that might be involved in the PDAC triggering. Surprisingly, strong evidence for the biological relevance of our results can be found in the literature.

LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis

“…Recent researches have also investigated LAMC2 as a valuable biomarker of cancer diagnosis. 36 37 Due to a limitation of the small sample size, we explored the expression of LAMC2 in various cancer types using (The Cancer Genome Atlas) TCGA database. The results showed that LAMC2 was upregulated in tumours and might be used as a biomarker for a variety of tumour types.…”

“…Recent researches have also investigated LAMC2 as a valuable biomarker of cancer diagnosis 36 37. Due to a limitation of the small sample size, we explored the expression of LAMC2 in various cancer types using (The Cancer Genome Atlas) TCGA database.…”

S100a9 might act as a modulator of the Toll-like receptor 4 transduction pathway in chronic rhinosinusitis with nasal polyps

“…In other words, a pair of genes participating in a comparable biological pathway during a particular biological condition might lose their connection under a different biological circumstance. As a result, the degree and pattern of gene expression correlation between a pair of genes can be influenced by internal changes and cellular conditions 12 . Therefore, pairwise interaction analyses, in the classical sense, may be too simplistic to explain complex molecular relationships 13 , 14 .…”