**8. Lgr5**

Leucine-rich repeat-containing G-protein coupled receptor 5 or Gpr49 is a receptor formed by eight main domains [69]. Lgr5 was identified on the cellular surface of intestinal and colonic stem cells and is being considered thus a biomarker of them [70]. Lgr5 overexpression was also confirmed in esophageal and colon cancer, in hepatocellular carcinoma, and in ovarian cancer [70].

Lgr5 is expressed in both normal and tumor colonic tissues [69]. In normal colon tissue, Lgr5 is expressed in a small area of the intestinal crypts. Its expression area increases with cell transformation in adenoma and is most elevated in colon adenocarcinoma [69]. The percentage of colon cancer patients expressing Lgr5 is, according to literature studies, around 80% [70, 71].

Overexpression of Lgr5 in colon cancer correlates with advanced stages of the disease [70, 71], with lymph node involvement (L) [70, 71] and perineural invasion [71] and distant metastases (M) [70]. Lgr5 involvement in cellular proliferation is also suggested due to the correlation found between Lgr5 expression and Ki-67 expression [70].

Lgr5 is thus considered to have a role in colon cancer development and progression and possibly in liver metastases formation as well [69]. Moreover, Lgr5 is considered to have a clinical role in predicting advanced pathological stages of colon cancer tumors [72].
