title: A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer?
abstract: Cancer stem cell (CSC) markers could serve as potential prognostic procedure. This study is aimed to investigate the local expression of doublecortin-like kinase 1 (DCLK1) and Lgr5 in colorectal cancer tissues (CRC) at both protein and messenger RNA (mRNA) level, followed by providing a comparison of the local and circulating expression pattern of these markers, based on our present and previous study. The mRNA expression level of DCLK1 and Lgr5 was evaluated using comparative real-time PCR method applying 58 fresh tumor tissues and their correspondent normal margins. Immunohistochemistry was applied to analyze the protein expression level of DCLK1 and Lgr5 in paraffin-embedded CRC tissues. The correlation of DCLK1 and Lgr5 expression pattern with clinicopathological characteristics was assessed. A higher mRNA expression level of DCLK1 (3.28-fold change, p < 0.001) and Lgr5 (2.29-fold change, p < 0.001) was observed in CRC fresh tissues compared to the normal adjacent margins, and the expression level was higher in patients with higher grade and stages of disease and patients who underwent neoadjuvant chemoradiotherapy (CRT). The protein expression level of DCLK1 and Lgr5 was also increased significantly in tumor tissues compared to normal colon tissues which were positively correlated to tumor stage and grade and neoadjuvant CRT. Taken together, the results of protein analysis were in accordance with mRNA assessment. The local expression pattern of DCLK1 and Lgr5 was also in accordance with their expression level in circulation. However, some minor inconsistencies were observed which may be attributed to several factors including the possible effect of CRT on CSC reprogramming.
authors.affiliation: Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Eastern side of Tehran University, 88, Italia St, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mirzaei
authors.affiliation: Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Eastern side of Tehran University, 88, Italia St, Tehran, Iran. g-tavoosi@tums.ac.ir.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Tavoosidana
authors.affiliation: Surgical Pathology Department, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Afshin Abdi
authors.initials: AA
authors.lastname: Rad
authors.affiliation: Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Rezaei
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Tavakoli-Yaraki
authors.affiliation: Department of Biotechnology, Faculty of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Azade Amini
authors.initials: AA
authors.lastname: Kadijani
authors.affiliation: Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Khalili
authors.affiliation: Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Zahra.madjd@yahoo.com.|Oncopathology Research Center, Iran University of Medical Sciences, Hemmat Street (Highway), Next to Milad Tower, Tehran, Iran. Zahra.madjd@yahoo.com.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Madjd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000089742:Doublecortin-Like Kinases; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C116884:LGR5 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases
keywords: Circulating cancer stem cell; Colorectal cancer; DCLK1; Lgr5; Local cancer stem cell