LGR5 expression predicts peritoneal recurrence after curative resection of primary colon cancer

Abstract

BACKGROUND: The aim of this study was to clarify whether a cancer stem cell marker could be an indicator of post-operative peritoneal recurrence of colon cancer. METHODS: Expression of four putative markers (CD133, CD44 variant 6, aldehyde dehydrogenase-1 and leucine-rich repeating G-protein-coupled receptor-5 (LGR5)) was evaluated immunohistochemically in primary tumour samples from 292 patients who underwent curative resection for non-metastasised pT4 colon cancer at the University of Tokyo Hospital between 1997 and 2015. RESULTS: Peritoneal recurrence was significantly higher in LGR5-negative cases (5-year cumulative incidence: 27.5% vs. 14.4%, p = 0.037). Multivariable analysis confirmed that negative LGR5 expression was an independent risk factor for peritoneal recurrence (hazard ratio (HR) 2.79, p = 0.005) in addition to poor differentiation, positive lymph node metastasis, preoperative carcinoembryonic antigen > 5 ng/mL and anastomotic leakage. The addition of LGR5 significantly improved the predictive value of the multivariable model (net reclassification improvement: 0.186, p = 0.028: integrated discrimination improvement: 0.047, p = 0.008). CONCLUSIONS: Negative LGR5 expression was a significant predictor of peritoneal recurrence in patients with pT4 colon cancer. Therefore, LGR5 might be a promising biomarker to identify patients at high risk of post-operative peritoneal metastasis.

Prognostic Impact of LGR5, Prox1, and Notch1 Biomarkers in Stage II to III Colon Cancer

“…Moreover, a different study has scored LGR5 expression in both the epithelium and stroma of the tumor 30. The current study demonstrated that LGR5 was significantly expressed in CC as compared with adjacent normal mucosa, which was comparable with the previous results 31,32. This observation was consistent with the role of LGR5 in carcinogenesis.…”

Clinicopathologic and Prognostic Significance of LGR5, a Cancer Stem Cell Marker in Patients With Colorectal Cancer

“…The reasons for termination of this clinical trial have not been made known publicly. Most recently Nagata et al [26] found that a negative LGR5 expression was a significant predictor of peritoneal recurrence in patients with pT4 colon cancer, while Sato et al [27] documented that there was a significant difference in OS between the LGR5-positive group and LGR5-negative group, with a Cox proportional hazards models revealing the LGR5-positive group as having a better OS.…”

Garcinone C Suppresses Tumorsphere Formation and Invasiveness by Hedgehog/Gli1 Signaling in Colorectal Cancer Stem-like Cells

“…These are involved in chemotherapy resistance and malignant tumor metastasis. 4,5 In addition, the OCT4, SOX2, and Nanog genes are overexpressed in CSCs and play a dominant role in maintaining and inducing pluripotency. 6 Thus, CSCs exhibit a renewable and differentiated ability leading to tumor growth, metastasis, chemotherapy resistance, and cancer relapse.…”

“…Accumulating evidence demonstrates that there is a small subpopulation of cancer stem-like cells (CSCs) in CRC with characteristics similar to embryonic stem cells (ESCs), which are associated with the progression and relapse of CRC. , CSC-related markers including aldehyde dehydrogenase (ALDH), CD44, CD133, and leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) have been identified in CRC. These are involved in chemotherapy resistance and malignant tumor metastasis. , In addition, the OCT4, SOX2, and Nanog genes are overexpressed in CSCs and play a dominant role in maintaining and inducing pluripotency . Thus, CSCs exhibit a renewable and differentiated ability leading to tumor growth, metastasis, chemotherapy resistance, and cancer relapse. , Therefore, targeting the CSCs is a novel approach in addressing cancer progression and prognosis.…”