Oncotarget

Research Papers:

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

Zhong Zheng, Huiping Yu, Qin Huang, Hongyan Wu, Yao Fu, Jiong Shi, Ting Wang and Xiangshan Fan _

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Oncotarget. 2018; 9:30025-30033. https://doi.org/10.18632/oncotarget.23144

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Abstract

Zhong Zheng1,*, Huiping Yu1,*, Qin Huang2, Hongyan Wu1, Yao Fu1, Jiong Shi1, Ting Wang1 and Xiangshan Fan1

1Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210000, P.R. China

2Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System and Harvard Medical School, Boston, MA, USA

*These authors contributed equally to this work

Correspondence to:

Xiangshan Fan, email: fxs23@hotmail.com

Keywords: colorectal cancer; Lgr5; heterogeneous expression; progression

Received: April 20, 2017     Accepted: November 14, 2017     Published: July 10, 2018

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.


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