In-Silico Analysis of Differentially Expressed Genes and Their Regulating microRNA Involved in Lymph Node Metastasis in Invasive Breast Carcinoma

Abstract

Introduction: Axillary nodal metastasis is related to poor prognosis in breast cancer (BC). The metastatic progression in BC is related to molecular signatures. The currently popular methods to evaluate nodal status may give false negatives or give rise to secondary complications. In this study, key candidate genes in BC lymph node metastasis have been identified from publicly available microarray datasets and their roles in BC have been explored through survival analysis and target prediction.Methods: Gene Expression Omnibus datasets have been analyzed for differentially expressed genes (DEGs) in lymph node-positive BC patients compared to nodal-negative and healthy tissues. The functional enrichment analysis was done in database for annotation, visualization and integrated discovery (DAVID). Protein-protein interaction (PPI) network was constructed in Search Tool for the Retrieval of Interacting Genes and proteins (STRING) and visualized on Cytoscape. The candidate hub genes were identified and their expression analyzed for overall survival (OS) in Gene Expression Profiling Interactive Analysis (GEPIA). The target miRNA and transcription factors were analyzed through miRNet.Results: A total of 102 overlapping DEGs were found. Gene Ontology revealed eleven, seventeen, and three significant terms for cellular component, biological process, and molecular function respectively. Six candidate genes, DSC3, KRT5, KRT6B, KRT17, KRT81, and SERPINB5 were significantly associated with nodal metastasis and OS in BC patients. A total of 83 targeting miRNA were identified through miRNet and hsa-miR-155-5p was found to be the most significant miRNA which was targeting five out of six hub genes. Conclusion:In-silico survival and expression analyses revealed six candidate genes and 83 miRNAs, which may be potential diagnostic markers and therapeutic targets in BC patients and miR-155-5p shows promise as it targeted five important hub genes related to lymph-node metastasis.

Identification of Genes Crucial for Biological Processes in Breast Cancer Liver Metastasis Relapse

“…Previous research has found that SHC2 is coding for the SHC-coding transforming protein 2, which associates with the cancer's start and later progression [11]. KRT6B regulates EMT and cytoskeletal dynamics, which were found to support cancer cell migration, proliferation, invasion, and metastasis [12]. SFRP2, a protein in the SFRP family, was found to act as a counter-direction signal from the Wnt/β type pathway, and is associated with various cancer incidences, including breast cancer [13].…”

Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review

“…In TNBC, a negative correlation between K17 RNA expression and outcome was found only in a subgroup of patients with invasive ductal carcinoma with large tumors and advanced stage [29]. A positive correlation between K17 and clinical outcome was found in breast [65,78] and gastric cancer [77]. Studies in pancreatic cancer [49] and primary central nervous system (CNS) lymphoma [79] found no correlation.…”

“…Five studies (21.7%) generated their own transcriptome data [38,42,51,52,79]. Thirteen studies reported an effect size in their findings [30,31,42,50,57,65,71,72,75,[78][79][80][81].…”