The Expression Analysis of Intestinal Cancer Stem Cell Marker Lgr5 in Colorectal Cancer Patients and the Correlation with Histopathological Markers

• Published in: Journal of gastrointestinal cancer Vol. 51; no. 2; pp. 591 - 599
• Main Authors: Salehizadeh, Shirin, Hasanzad, Mandana, Kadijani, Azade Amini, Akbari, Abolfazl
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2020
• Subjects: Biomarkers, Tumor - metabolism; Cancer Research; Case-Control Studies; Colorectal Neoplasms - physiopathology; Female; Gastroenterology; Gene Expression Regulation, Neoplastic - genetics; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplastic Stem Cells - metabolism; Oncology; Original Research; Prognosis; Radiotherapy; Receptors, G-Protein-Coupled - metabolism; Cancer stem cell; Angiogenesis; Lrig1; Lgr5; Proliferation; Colorectal cancer
• ISSN: 1941-6628; 1941-6636; 1941-6636
• DOI: 10.1007/s12029-019-00295-w

Introduction Cancer stem cells (CSCs) have frequently been utilized in the cell characterization and identified responsible for tumor development, metastasis, recurrence, and chemoresistance. CSC surface markers function in cancer cell signaling and are indicated as potential biomarkers for cancer diagnosis and prognosis. As well, dysregulation of cancer-related signaling pathways could promote CSC development and progression. Our aim was to evaluate the expression of colorectal CSC markers and their correlation with cancer proliferation and angiogenesis. Methods In this case-control study, total RNA was extracted from a total of 74 colorectal tumors and 74 adjacent normal tissue biopsies. Then, using a quantitative real-time PCR, the relative expression levels of Lgr5 and Lrig1 were measured in all malignant and healthy samples. Also, immunohistochemical (IHC) staining of tumor tissues was performed for Ki-67 (proliferation) and CD34 (angiogenesis) markers, and the immunoexpression staining scores were obtained. The diagnostic value of the genes was evaluated using receiver operating characteristic (ROC) curve. Possible correlation between CSC markers and immunohistochemical markers in CRC was analyzed by Pearson’s correlation test and linear regression. Results The expression level of Lgr5 in tumor samples showed a significant increase compared with normal samples ( p  < 0.001) with a fold change of 2.54 (± 0.182). However, there was no significant difference in the relative expression of Lrig1 gene in tissue samples of healthy subjects and patients. The analysis of the ROC showed an AUC of 0.92 for Lgr5 and sensitivity 80% and specificity 96%. Further analysis revealed a significant correlation between mRNA levels of Lgr5 and immunoexpression of Ki-67 ( r 2  = 0.680, p  < 0.001). Conclusion The high expression levels of Lgr5 found in tumor tissues were correlated with histological parameters, indicating a significant role in CRC development and diagnosis.