British journal of cancer · 2019
LGR5 expression predicts peritoneal recurrence after curative resection of primary colon cancer.
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Nagata Hiroshi, Ishihara Soichiro, Abe Hiroyuki, Ushiku Tetsuo, Kishikawa Junko, Tanaka Toshiaki, Hata Keisuke, Kawai Kazushige, Fukayama Masashi, Nozawa Hiroaki
Аннотация
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.
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.
Предметные рубрики MeSH
AC133 AntigenAgedBiomarkers, TumorCarcinoembryonic AntigenColonic NeoplasmsFemaleGPI-Linked ProteinsGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingNeoplastic Stem CellsPeritoneal NeoplasmsPeritoneumPrognosisReceptors, G-Protein-Coupled