Heterogeneous expression of Lgr5 as a risk factor for focal invasion and distant metastasis of colorectal carcinoma

Oncotarget. 2018 Jul 10;9(53):30025-30033. doi: 10.18632/oncotarget.23144.

Abstract

Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a downstream target gene of the Wnt/β-catenin signaling pathway and identified as a marker of cancer stem-like cells of colorectal carcinoma (CRC). Here, the heterogeneous expression pattern of Lgr5 and its clinical significance were studied by the method of immunohistochemistry in 204 CRC tumors at various pTNM stages. Lgr5 expression was found in 82.4% (168/204) cases, significantly more common in neoplastic cells at the infiltrative front (n = 59.5%, 110/185) or at the expanding front (n = 36.4%, 59/162) than at the tumor center (n = 16.7%, 34/204; P < 0.01). Tumor budding (TB) was discovered with significantly higher Lgr5 expression (n = 39.3%, 57/145, P = 0.03) and significantly positively correlated between Lgr5 expression and TB grade (r = 0.19, P = 0.02). Additionally, both positive Lgr5 expression and a high TB grade were significantly correlated to the depth of tumor invasion, lymph node metastasis, pTNM stage, and perineural invasion (P < 0.01). The study results suggest that heterogeneous expression of Lgr5 may be a risk factor for local invasion and distant metastasis of CRC.

Keywords: Lgr5; colorectal cancer; heterogeneous expression; progression.