• Investigating proteins secreted by extracellular vesicles involved in intercellular communication in the liver tumor microenvironment
  • Shima Parastari Farkoosh,1,* Issa Layali,2 Zahra Ramezani,3 Fatemeh Karimi,4 Saghar Mousavi,5
    1. Inspection and Performance Evaluation Office, Iranian Blood Transfusion Organization, Tehran, Iran
    2. Department of Biochemistry and Biophysics, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
    3. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
    4. Department of Cellular and Molecular Biology, Faculty of Advanced Sciences and technology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
    5. Department of Cellular and Molecular Biology, Faculty of Advanced Sciences and technology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran


  • Introduction: Cancer is a multifactorial disease caused by multiple environmental and genetic factors (1). Genes involved in cancer are classified into several groups including proto-oncogenes, tumor suppressor genes, genes involved in genome stability and cell migration. Tumor-enveloping environment (TME) has a similar function as stem cells, which affects tumor progression and metastasis. Studying the nature of this environment is effective in the diagnosis and molecular treatment of cancer and provides valuable and new information for the control of tumor malignancy and risk assessment. Exosomes are vesicles of size (30-150 nm) released by cells into the extracellular space and act as intercellular signal vectors through the horizontal transfer of biological molecules including microRNA (miRNA). Cancer treatment is not enough regardless of the type of tumor, the nature of tumor cells and stem cells, the surrounding environment of the tumor, the cellular and molecular communication between the tumor and its surrounding environment, the type of treatment and how to use it (7). Therefore, this disease cannot be recognized and treated only on the basis of pathology and surgery, radiotherapy or chemotherapy. Early detection approach in the community helps in targeted treatment along with cost reduction. Today, BIOM science relies on genome, transcriptome, proteome, signalome and other cellular systems to help detect disease- causing biomarkers, which can be traced back months and even years by having the biomarker panel pattern in hand. He found and studied molecular changes and cellular changes in cells that initiate the process of becoming cancerous. In the division of different stages of liver cancer, currently, only tumor size, involvement of lymph nodes and metastasis to the surrounding tissues are criteria for the division of the staging of this disease (9) and the treatment is based only on this. invoices. Since currently determining the treatment plan for a metastatic patient, in the process of its definitive control and treatment, is only based on standard and traditional PET scan variables, it is not possible to preventively and in a short time in the treatment plan for patients with tumor metastases. made a decision and almost the process of treatment and medicine will occur in the upper stages. Therefore, in this study, we are trying to rely on the science of amics and specifically proteomics, to obtain specific protein biomarkers from the secretion of extracellular exosomes, which are evidence for the initiation of tumor metastasis, and to identify their proteome profile. do. To finally propose molecular variables to the medical community to design a treatment plan in the control of liver metastases and finally increase the survival of patients.
  • Methods: The variables investigated in this study are proteome, which is used to determine the concentration of samples with a spectrophotometer, and separation is done with a two-dimensional gel electrophoresis device. The comparison tool is the gels obtained from metastatic liver tissue and the altered proteins are identified with R software. Determining the validity of the tool: Two-dimensional gel electrophoresis is one of the reliable methods for proteome separation and protein expression measurement (it compares protein spots with the help of gel analysis software)
  • Results: The results of these studies help to understand the contribution of myome and proteome-based intercellular communication in tumor behavior. Based on these findings, the enrichment of the engineered myoma panel can contribute to key mediators, such as MET, PIK3CA, and CDKN2A, to modulate critical processes involved in tumor growth, such as metastasis or angiogenesis. This study was one of the first studies of the coordinated investigation of miromics and proteomics with a computational biology approach, which tried to establish the close relationship between proteins and proteins. However, further studies should be conducted to discover other downstream targets of the myome panel and proteome introduced in this research in the liver TME.
  • Conclusion: Since currently determining the treatment plan for a metastatic patient, in the process of its definitive control and treatment, is only based on standard and traditional molecular imaging variables, it is not possible to preventively and in a short time in the treatment plan For patients with breast tumor metastases, a decision was made and almost the treatment and medication process will occur in the upper stages. Therefore, in this study, we tried to rely on the science of OMICS and specifically proteomics, to obtain specific protein biomarkers from the secretion of extracellular exosomes, which are evidences for the initiation of tumor metastasis, and to identify their proteome profile. To finally propose molecular variables to the medical community to design a treatment plan in the control of metastasis and finally increase the survival of patients.
  • Keywords: Exosomes R software, machine learning and clustering, proteomics, biological pathways