Integrative ontology and pathway-based approach identifies distinct molecular signatures in transcriptomes of esophageal squamous cell carcinoma
Author | Udhaya Kumar, S. |
Author | Balasundaram, Ambritha |
Author | Anu Preethi, V. |
Author | Chatterjee, Sayoni |
Author | Kameshwari Gollakota, G.V. |
Author | Kashyap, Manoj Kumar |
Author | George Priya Doss, C. |
Author | Zayed, Hatem |
Available date | 2022-12-15T08:24:44Z |
Publication Date | 2022 |
Publication Name | Advances in Protein Chemistry and Structural Biology |
Resource | Scopus |
Abstract | Esophageal squamous cell carcinoma (ESCC) remains a serious concern globally due to many factors that including late diagnosis, lack of an ideal biomarker for diagnosis and prognosis, and high rate of mortality. In this study, we aimed to identify the essential dysregulated genes and molecular signatures associated with the progression and development of ESCC. The dataset with 15 ESCCs and the 15 adjacent normal tissue samples from the surrounding histopathologically tumor-free mucosa was selected. We applied bioinformatics pipelines including various topological parameters from MCODE, CytoNCA, and cytoHubba to prioritize the most significantly associated DEGs with ESCC. We performed functional enrichment annotation for the identified DEGs using DAVID and MetaCore GeneGo platforms. Furthermore, we validated the essential core genes in TCGA and GTEx datasets between the normal mucosa and ESCC for their expression levels. These DEGs were primarily enriched in positive regulation of transferase activity, negative regulation of organelle organization, cell cycle mitosis/S-phase transition, spindle organization/assembly, development, and regulation of angiogenesis. Subsequently, the DEGs were associated with the pathways such as oocyte meiosis, cell cycle, and DNA replication. Our study identified the eight-core genes (AURKA, AURKB, MCM2, CDC20, TPX2, PLK1, FOXM1, and MCM7) that are highly expressed among the ESCC, and TCGA dataset. The multigene comparison and principal component analysis resulted in elevated signals for the AURKA, MCM2, CDC20, TPX2, PLK1, and FOXM1. Overall, our study reported GO profiles and molecular signatures that might help researchers to grasp the pathological mechanisms underlying ESCC development and eventually provide novel therapeutic and diagnostic strategies. 2022 Elsevier Inc. |
Sponsor | The authors would like to take this opportunity to thank the management of Vellore Institute of Technology (VIT), Vellore, India, Qatar University, Doha, Qatar, and Amity University, Haryana, Gurugram for providing the necessary facilities and encouragement to carry out this work. SUK, HZ, and CGPD were involved in the design of the study. SUK, AB, and VAP were involved in the data collection and conducted the experiment. SUK, AB, VAP, MKK, and CGPD were involved in the acquisition, analysis, and interpretation of the results. SUK and AB drafted the manuscript. CGPD and HZ supervised the entire study and were involved in study design, the acquisition, analysis, understanding of the data, and critically reviewed the manuscript. All authors edited and approved the submitted version of the article. The authors have declared that no conflicts of interest exist. |
Language | en |
Publisher | Elsevier |
Subject | Cancer Differentially expressed genes Esophageal squamous cell carcinoma MetaCore Protein-protein interaction TopGO |
Type | Book chapter |
Pagination | 177-206 |
Volume Number | 131 |
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