ABSTRACT
Cancer stem cells (CSCs) are thought to be a major player in tumor initiation, progression, and metastasis. Targeting CSCs for elimination presents a promising therapeutic strategy; however, this approach will require a stronger understanding of CSC biology and identification of CSC-specific markers. The present study was conducted to examine the correlation between DCLK1 and miR-137 and miR-15a levels in colorectal cancer. A total of 222 samples, including 181 colorectal cancer specimens, 24 adenomatosis, and 17 non-adenomatosis colonic polyps, were stained for DCLK1 expression using immunohistochemistry. Also, expression of miR-137 and miR-15a was assessed in colorectal cancer with high and low DCLK1 expression levels. Most colorectal cancer specimens (76%) showed strong expression of DCLK1, whereas only 21% of adenomatous and none of non-adenomatous colonic polyps showed strong DCLK1 expression. A significant difference in DCLK1 expression was found between colorectal cancer, adenomatous, and non-adenomatous colonic polyps (P < 0.001). Higher expression of DCLK1 was more frequently detected in colorectal cases with larger tumor size (P = 0.03), poor differentiation (P = 0.03), and lymph node involvement (P = 0.04). Comparison of miR-137 and miR-15a in colorectal cancer cases revealed a significant inverse correlation with DCLK1 expression (P = 0.03 and P = 0.04, respectively). DCLK1 may act as a candidate marker for colorectal cancer stem cells. The critical role of DCLK1 in colorectal cancer suggests that it may represent an early diagnostic marker and therapeutic target; however, further investigation is warranted.
Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/pathology , Intracellular Signaling Peptides and Proteins/metabolism , MicroRNAs/genetics , Neoplastic Stem Cells/pathology , Protein Serine-Threonine Kinases/metabolism , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Disease Progression , Doublecortin-Like Kinases , Female , Follow-Up Studies , Humans , Intracellular Signaling Peptides and Proteins/genetics , Male , Middle Aged , Neoplasm Invasiveness , Neoplastic Stem Cells/metabolism , Prognosis , Protein Serine-Threonine Kinases/geneticsABSTRACT
Aim: There is no consensus regarding the clinical significance of CD44 and CD24 as cancer stem cell (CSC) marker in colorectal cancer (CRC). Methodology: A total of 494 CRC samples (2008-2017) were assessed for CD44 (epithelial isoform) and CD24 expression using tissue microarray. Results: CD24 individually or in combination with CD44 was not associated with any of the clinicopathologic characteristics of the tumor. CD44 expression was inversely associated with pathological Tumor, Node, Metastasis (pTNM) lower stages (p = 0.038) and lymphatic invasion (p = 0.05). Conclusion: In summary, the epithelial isoform of CD44 is inversely associated with invasive characteristics of CRC.