Early adaptation of colorectal cancer cells to the peritoneal cavity is associated with activation of ‘stemness’ programs and local inflammation

Jorge Barriuso, Raghavendar Nagaraju, Shreya Belgamwar, Bipasha Chakrabarty, George Burghel, Helene Schlecht, Lucy Foster, Elaine Kilgour, Andrew J. Wallace, Michael Braun, Caroline Dive, D Gareth Evans, Robert Bristow, Mark Saunders, Sarah O'Dwyer, Omer Aziz

Research output: Contribution to journalArticlepeer-review


PURPOSE: At diagnosis, colorectal cancer presents with synchronous peritoneal metastasis in up to 10% of patients. The peritoneum is poorly characterized with respect to its super-specialised microenvironment. Our aim was to describe the differences between peritoneal metastases and their matched primary tumours excised simultaneously at the time of surgery. Also, we tested the hypothesis of these differences being present in primary colorectal tumours and having prognostic capacity.

EXPERIMENTAL DESIGN: We report a comprehensive analysis of thirty samples from peritoneal metastasis with their matched colorectal cancer primaries obtained during cytoreductive surgery. We tested and validated the prognostic value of our findings in a pooled series of 660 colorectal cancer primary samples with overall survival (OS) information and 743 samples with disease free survival (DFS) information from publicly available databases.

RESULTS: We identified 20 genes dysregulated in peritoneal metastasis that promote an early increasing role of 'stemness' in conjunction with tumour favourable inflammatory changes. When adjusted for age, gender and stage, the 20-gene peritoneal signature proved to have prognostic value for both OS (adjusted-hazard ratio (HR) for the high-risk group (vs low-risk) 2.32 (95% confidence interval (CI) 1.69-3.19; p-value < 0.0001)) and for DFS (adjusted-HR 2.08 (95%CI 1.50-2.91; p-value < 0.0001)).

CONCLUSIONS: Our findings indicated that the activation of "stemness" pathways and adaptation to the peritoneal specific environment are key to early stages of peritoneal carcinomatosis. The in-silico analysis suggested that this 20-gene peritoneal signature may hold prognostic information with potential for development of new precision medicine strategies in this setting.

Original languageEnglish
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Early online date30 Nov 2020
Publication statusE-pub ahead of print - 30 Nov 2020


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