Abstract
BackgroundThe 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.MethodsExpression 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.ResultsPeritoneal 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).ConclusionsNegative 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.
Highlights
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
Since there is no definitive determinant of cancer stem cells, we evaluated the expression of four putative stem cell markers, namely, CD133, CD44 variant 6 (CD44v6), aldehyde dehydrogenase-1 (ALDH1) and leucine-rich repeating G-proteincoupled receptor-5 (LGR5) and investigated whether they were effective clinical biomarkers to identify patients with a high risk of post-operative peritoneal metastasis
The expression of CD44v6, ALDH1 and LGR5 was recognised at the bottom of a normal colonic crypt, compatible with the site of stem cells
Summary
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. Despite significant advances in treatments for colorectal cancer, the prognosis of patients with peritoneal metastasis remains dismal.[1] the prognosis is strongly affected by the extent of carcinomatosis, detection of the disease in its early stage is still challenging due to the poor diagnostic sensitivity of current imaging modalities. In view of these difficulties, aggressive preventive measures against post-operative peritoneal metastasis were advocated, including upfront hyperthermic intraperitoneal chemotherapy or a systematic second-look operation.[2,3] High-risk patients may benefit from the interventions, whereas patient selection is the key. We assumed that peritoneal metastasis was compatible with the characteristics of cancer stem cells because tumour initiation and proliferation abilities are required to form each peritoneal nodule, and they are known to be resistant to chemotherapy
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