Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer.
Biomarkers, Tumor
/ blood
Colorectal Neoplasms
/ blood
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Inflammation
/ blood
Interleukin-6
/ blood
Interleukin-8
/ blood
Male
MicroRNAs
/ blood
Middle Aged
Neoplasm Metastasis
Neoplasm Recurrence, Local
/ blood
Prognosis
Recurrence
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
06
03
2018
accepted:
27
11
2018
revised:
03
10
2018
pubmed:
15
1
2019
medline:
13
11
2019
entrez:
15
1
2019
Statut:
ppublish
Résumé
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. 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". 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 30636774
doi: 10.1038/s41416-018-0360-y
pii: 10.1038/s41416-018-0360-y
pmc: PMC6353894
doi:
Substances chimiques
Biomarkers, Tumor
0
Interleukin-6
0
Interleukin-8
0
MIRN21 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
340-345Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172670
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA178744
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA182905
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA184843
Pays : United States
Organisme : NCATS NIH HHS
ID : UH3 TR000943
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA187238
Pays : United States
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