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Comprehensive Multi-Omics Analysis Reveals Npc2 and Itgav Genes As Potential Prognostic Biomarkers in Gastrointestinal Cancers Publisher



Piroozkhah M1 ; Zabihi M2 ; Jalali P1 ; Salehi Z3
Authors
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Authors Affiliations
  1. 1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Institute of Biochemistry and Biophysics (IBB), Department of Bioinformatics, Laboratory of Complex Biological Systems and Bioinformatics (CBB), University of Tehran, Tehran, Iran
  3. 3. Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran

Source: Cancer Reports Published:2024


Abstract

Background: Gastrointestinal cancers (GICs) continue to dominate in terms of both incidence and mortality worldwide. Due to the absence of efficient and accurate prognostic biomarkers, the prognosis and treatment outcomes of many GICs are poor. Identifying biomarkers to predict individual clinical outcomes efficiently is a fundamental challenge in clinical oncology. Although several biomarkers have been continually discovered, their predictive accuracy is relatively modest, and their therapeutic use is restricted. In light of this, the discovery of reliable biomarkers for predicting prognosis and outcome in GIC is urgently required. Materials and Methods: We evaluated the Human Protein Atlas dataset and identified NPC Intracellular Cholesterol Transporter 2 (NPC2) and Integrin Subunit Alpha V (ITGAV) as probable poor predictive genes for these cancers. In addition, we used the GEPIA2, cBioPortal, UALCAN, LinkedOmics, STRING, Enrichr, TISDB, TIMER2.0, hTFTarget, miRTarBase, circBank, and drug–gene interaction database databases to conduct a comprehensive and systematic analysis of the NPC2 and ITGAV genes. Result: Our results found high expression levels of NPC2 and ITGAV in most GICs. The aforementioned gene expressions were linked to several clinicopathological characteristics of GICs as well as poorer prognosis in LIHC and STAD. The most common alteration type of NPC2 was amplification, and for ITGAV was deep deletion. Significant promotor hypermethylation was also seen in NPC2 and ITGAV in PAAD and COAD, respectively. For the immunologic significance, NPC2 and ITGAV were positively correlated with the abundance of tumor-infiltrating lymphocytes and macrophages. Furthermore, various immunomodulators showed strong correlations with the expression of these genes. There were currently 10 small molecule drugs targeting ITGAV. Conclusion: Consequently, our bioinformatics analysis showed that NPC2 and ITGAV might be used as potential biomarkers to determine the prognosis of various GICs and are also related to immune infiltration. © 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.
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