1. Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer
- Author
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Masayoshi Shimizu, Michael J. Overman, David G. Menter, George A. Calin, Hai T. Tran, Scott Kopetz, John V. Heymach, Jean Nicolas Vauthey, Rosa Lizeth Frias, Neeraj Shah, Anastasia D. Katsiampoura, Michael Lam, Jennifer S. Davis, Andreas Varkaris, Cristina Ivan, Jeffrey S. Morris, and Yun Shin Chun
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,Population ,Inflammation ,Disease ,Gastroenterology ,Article ,Disease-Free Survival ,Tumour biomarkers ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Recurrence ,Internal medicine ,Biomarkers, Tumor ,Medicine ,Humans ,Neoplasm Metastasis ,education ,education.field_of_study ,Predictive marker ,business.industry ,Proportional hazards model ,Interleukin-6 ,Interleukin-8 ,Middle Aged ,medicine.disease ,Prognosis ,3. Good health ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Female ,medicine.symptom ,Neoplasm Recurrence, Local ,business ,Colorectal Neoplasms - 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
- Published
- 2019