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The potential role of platelets in the consensus molecular subtypes of colorectal cancer

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Abstract

The consensus molecular subtypes (CMS) in colorectal cancer (CRC) represent distinct molecular subcategories of disease as reflected by comprehensive molecular profiling. The four CMS subtypes represent unique biology. CMS1 represents high immune infiltration. CMS2 demonstrates upregulation of canonical pathways such as WNT signaling. Widespread metabolic changes are seen in CMS3. CMS4 represents a mesenchymal phenotype with hallmark features including complement activation, matrix remodeling, angiogenesis, epithelial-mesechymal transition (EMT), integrin upregulation and stromal infiltration. In contrast to this new paradigm, a number of observations regarding CRC remain disconnected. Cancers are associated with thrombocytosis. Venous thromboembolic events are more likely in malignancy and may signify worse prognosis. Aspirin, an anti-platelet agent, has been linked in large observational studies to decrease incidence of adenocarcinoma and less advanced presentations of cancer, in particular CRC. Inflammatory bowel disease is a risk factor for CRC. Gross markers to recognize the immunothrombotic link such as the platelet to lymphocyte ratio are associated with poorer outcomes in many cancers. Platelets are increasingly recognized for their dual roles in coordinating the immune response in addition to hemostasis. Here, we explore how these different but related observations coalesce. Platelets, as first responders to pathogens and injury, form the link between hemostasis and immunity. We outline how platelets contribute to tumorigenesis and how some disconnected ideas may be linked through inflammation. CMS4 through its shared mechanisms has predicted platelet activation as a hallmark feature. We demonstrate a platelet gene expression signature that predicts platelet presence within CMS4 tumors.

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Acknowledgements

Grant and other support: Boone Pickens Distinguished Chair for Early Prevention of Cancer, Duncan Family Institute, Colorectal Cancer Moon Shot, P30CA016672-41, 1R01CA187238-01, 5R01CA172670-03 and 1R01CA184843-01A1 and CA177909.

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The authors declare that they have no conflicts of interest.

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  1. Michael Lam and Jason Roszik contributed equally to this work.

Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, M. D. Anderson Cancer, Unit 0426, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Michael Lam, Preeti Kanikarla-Marie, Scott Kopetz & David G. Menter

  2. Department of Melanoma Medical Oncology, M. D. Anderson Cancer Center, Unit 430, 1515 Holcombe Blvd, Houston, 77030, TX, USA

    Jason Roszik

  3. Department of Epidemiology, M. D. Anderson Cancer Center, Unit 1340, 1515 Holcombe Blvd, Houston, 77030, TX, USA

    Jennifer S. Davis

  4. Department of Biostatistics, M. D. Anderson Cancer Center, Unit 1411, 1515 Holcombe Blvd, Houston, 77030, TX, USA

    Jeffrey Morris

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Correspondence to David G. Menter.

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Lam, M., Roszik, J., Kanikarla-Marie, P. et al. The potential role of platelets in the consensus molecular subtypes of colorectal cancer. Cancer Metastasis Rev 36, 273–288 (2017). https://doi.org/10.1007/s10555-017-9678-9

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