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  • The interaction of lncRNA and mRNA in Esophageal Squamous Cell Carcinoma

  • mohammad sadra maratebi shadbad,1 Amir karrari,2 Fatemeh Zeinali,3,*
    1. Research institute of Bioscience and Biotechnology, University of Tabriz Iran
    2. Research institute of Bioscience and Biotechnology, University of Tabriz Iran
    3. Department of Biological Science ,Faculty of Basic Sciences, Higher Education institute of Rabe Rashid , Tabriz Iran


  • Introduction: Esophageal squamous cell carcinoma (ESCC), a highly aggressive malignancy, accounts for 85% of the 604,100 new esophageal cancer cases reported globally in 2020. Originating from squamous epithelial cells, ESCC is often diagnosed at advanced stages, resulting in a 5-year survival rate of 15–25%. Projections estimate over 806,000 new cases by 2040, underscoring the need for improved strategies. Long non-coding RNAs (lncRNAs) have emerged as critical regulators in ESCC, modulating proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Dysregulated lncRNA expression drives tumorigenesis, offering potential as diagnostic and prognostic biomarkers. Advances in nanotechnology and immunotherapy highlight lncRNAs as therapeutic targets to overcome drug resistance. By interacting with pathways like Wnt and p53, lncRNAs influence cancer cell survival or programmed cell death. This section reviews ESCC’s epidemiological burden, the molecular roles of lncRNAs, and their promise in personalized diagnostics and treatments for high-risk populations.
  • Methods: This study analyzed microarray data from the NCBI Gene Expression Omnibus (GEO) dataset GSE157808, including 10 samples (5 ESCC tumors and 5 normal esophageal squamous cells), to explore lncRNA-mRNA interactions. Raw data from Agilent’s Microarray 2.0 platform were preprocessed using Robust Multi-Array Averaging (RMA) for normalization and LOG2 transformation. Differentially expressed lncRNAs (DElncRNAs) were identified with a P-value < 0.05 threshold using the GEO package. The Robust Rank Aggregation (RRA) method integrated DElncRNA lists, ranking genes by P-values and Fold Change (FC) with PDFR-adjusted P-values to minimize false positives. Subnetwork modules were analyzed using the MCODE plugin in Cytoscape, and hierarchical cluster analysis via the ggplot2 package in R revealed expression patterns. This methodology enabled a robust investigation of lncRNA regulatory roles in ESCC.
  • Results: Analysis of the GSE157808 microarray dataset identified 75,218 differentially expressed genes in ESCC, with 38,973 upregulated and 36,245 downregulated (logFC between -5 and 5, P-value < 0.05). Principal Component Analysis (PCA) and correlation analysis validated sample quality. A regulatory network, constructed using Cytoscape, elucidated interactions between pathways (PI3K/AKT, EMT, TGF-β) and downregulated genes, including MMP1, CST1, and MMP13. Box plots displayed raw and normalized sample distributions, while volcano plots visualized gene expression, confirming reduced tumor expression compared to controls. These results highlight lncRNAs’ role in modulating critical pathways and gene expression, contributing to ESCC progression and offering insights into potential molecular targets.
  • Conclusion: Esophageal squamous cell carcinoma (ESCC), a leading cause of cancer mortality, maintains a 5-year survival rate of 15–25%. This study underscores long non-coding RNAs (lncRNAs) as key regulators in ESCC, modulating downregulated genes like MMP1, CST1, and MMP13, linked to PI3K/AKT, EMT, and TGF-β pathways. Despite extensive research, ESCC’s molecular mechanisms, including its onset and therapeutic resistance, remain unclear. Using GEO microarray data and Cytoscape-based network analysis, this study confirms lncRNAs’ potential as biomarkers and therapeutic targets. These findings advocate for advanced bioinformatics to bridge gaps in understanding ESCC’s biology, paving the way for personalized diagnostics and treatments to address this aggressive malignancy’s global burden.
  • Keywords: LncRNA , mRNA ,Esophageal Squamous Cell Carcinoma

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