مقالات پذیرفته شده در سومین کنگره بین المللی زیست پزشکی
Common Molecular Markers between Circulating Tumor Cells and Blood Exosomes in Colorectal Cancer: A Systematic and Analytical review
Common Molecular Markers between Circulating Tumor Cells and Blood Exosomes in Colorectal Cancer: A Systematic and Analytical review
Somayeh Vafaei,1Fahimeh Fattahi,2marzieh ebrahimi,3Zahra Madjd,4,*
1. Department of Molecular Medicine, Faculty of advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. 2. Department of Molecular Medicine, Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. 3. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. 4. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
Introduction: Nearly half of patients with colorectal cancer (CRC), the third leading cause of cancer deaths worldwide, are diagnosed in the late stages of the disease. Appropriate treatment is not applied in a timely manner and nearly 90% of patients who experience metastasis ultimately die. Existing histopathological and molecular classifications are insufficient for prediction of metastasis, which limits approaches to treatment. Detection of reliable cancer-related biomarkers can improve early diagnosis, prognosis, treatment response prediction, and recurrence risk. Circulating tumor cells (CTCs) and exosomes in peripheral blood can be used in a liquid biopsy to assess the status of a tumor. Exosomes are abundant and available in all fluids of the body, have a high half-life and are released by most cells. Tumor-derived exosomes are released from primary tumors or CTCs with selective cargo that represents the overall tumor.
Methods: The systematic review highlights new trends and approaches in the detection of CRC biomarkers to determine tumor signatures using CTC and exosomes. When these are combined, they could be used to guide molecular pathology and can revolutionize detection tools. Relevant observational studies published up to July 24th, 2019 that evaluated the expression of tumor markers in CTCs and exosomes were searched in PubMed, Scopus, Embase and ISI Web of Science.
Results: The extracted biomarkers were applied in String and EnrichR for analysis to expand understanding. Evidence related to the diagnosis of CRC by means of CTC markers was addressed in 38 articles and 54 articles discussed the prognosis of CRC using CTC markers. Only 14 articles examined exosomes, five about diagnosis and nine about prognosis. Our results show that the most common markers introduced in CTCs were CEA (35 of 94 studies) and CK20 (33 of 94 studies), especially using qRT-PCR. Most markers investigated for exosomes, in addition to CD9, CD81, ALIX, and TSG101, were including EPCAM and HSP, especially using ultracentrifugation. Comparison of 131 CTC markers and 45 exosomes markers showed only three common markers (CEA, CD9, and EPCAM) on the gene list as diagnostic and prognostic biomarkers.
Conclusion: A half-century-old investigation of CEA in CRC was the first step in the identification of a much larger family of 12 CEACAMs. CEA is involved in the metastatic cascade process through positive regulation of cell migration and invasion; thus, the monitoring of CEA as a cost-effective and frequent indicator of recurrence of CRC has been investigated for years.
Integrin on tumor exosomes may play an important role in modulating organ-specific metastasis in cancer progression. CD9 is a member of the tetraspanin superfamily commonly detected in all types of exosomes involved in pathophysiologic processes such as cellular adhesion, growth, motility, cell-cell fusion, signal transduction, and tumor metastasis.
EPCAM is a membranous glycoprotein that is a CSC marker in tumor cells in the basolateral surface of most normal epithelial tissue and its role is to connect cells by means of calcium. The first step in metastasis is the separation of cancerous cells from primary tumors. CEA, CD9, and EPCAM are closely correlated with tumor progression as a poor prognostic factor and is required for the survival of CTCs in some cancers. Taken together, it appears that the signature of the CTC and exosome biomarkers are similar and follow common pathways; thus, exosomes can be applied as alternative tools for guiding better molecular pathology in the fight against cancer.
Precision medicine is changing clinical practice by tailoring treatment based on an individual’s genetic makeup. Recent studies have shown that CTC and ctDNA (circulating tumor DNA) provide complementary information and the use of both approaches to study tumor metastasis is warranted. CTC and exosomes can pave a path as diagnostic and prognostic procedures using the heterogeneity of tumor sites as they are released into the blood from live origins and can be analyzed at the DNA, RNA and protein levels. It is undeniable that more investigation is needed to compare them, especially for cancer patients.