Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-01-14

AUTHORS

Andreas Varkaris, Anastasia Katsiampoura, Jennifer S. Davis, Neeraj Shah, Michael Lam, Rosa Lizeth Frias, Cristina Ivan, Masayoshi Shimizu, Jeffrey Morris, David Menter, Michael Overman, Hai Tran, John Heymach, Yun Shin Chun, Jean-Nicolas Vauthey, George Calin, Scott Kopetz

ABSTRACT

BACKGROUND: Metastatic colorectal cancer (mCRC) is a highly heterogeneous disease from a clinical, molecular, and immunological perspective. Current predictive models rely primarily in tissue based genetic analysis, which not always correlate with inflammatory response. Here we evaluated the role of a circulating inflammatory signature as a prognostic marker in mCRC. METHODS: Two hundred eleven newly diagnosed patients with mCRC were enrolled in the study. One hundred twenty-one patients had unresectable metastases, whereas ninety patients had potentially resectable liver metastases at presentation. Analysis of miR-21, IL-6, and IL-8 in the plasma of peripheral blood was performed at baseline. Patients with high circulating levels of ≥2 of the three inflammation markers (miR-21, IL-6, and IL-8) were considered to have the "Inflammation phenotype-positive CISIG". RESULTS: Positive CISIG was found in 39/90 (43%) and 50/121 (45%) patients in the resectable and unresectable cohort, respectively. In the resectable population the median relapse-free survival was 18.4 compared to 31.4 months (p = 0.001 HR 2.09, 95% CI 1.2-3.67) for positive vs. negative CISIG. In contrast, the individual components were not significant. In the same population the median overall survival was 46.2 compared to 66.0 months (p = 0.0003, HR 2.57, 95% CI 1.26-5.27) for positive vs. negative CISIG, but not significant for the individual components. In the unresectable population, the median overall survival was 13.5 compared to 25.0 months (p = 0.0008, HR 2.49, 95% CI 1.46-4.22) for positive vs. negative CISIG. IL-6 was independently prognostic with overall survival of 16.2 compared to 27.0 months (p = 0.004, HR 1.96, 95% CI 1.24-3.11) for high vs. low IL-6, but not the other components. Using a Cox regression model, we demonstrated that CISIG is an independent predictive marker of survival in patients with unresectable disease (HR 1.8, 95% CI 1.2, 2.8, p < 0.01). CONCLUSION: In two different cohorts, we demonstrated that CISIG is a strong prognostic factor of relapse-free and overall survival of patients with mCRC. Based on these data, analysis of circulating inflammatory signaling can be complimentary to traditional molecular testing. More... »

PAGES

1-6

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41416-018-0360-y

DOI

http://dx.doi.org/10.1038/s41416-018-0360-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111273773

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30636774


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