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Circulating Levels of the Interferon-γ-Regulated Chemokines CXCL10/CXCL11, IL-6 and HGF Predict Outcome in Metastatic Renal Cell Carcinoma Patients Treated with Antiangiogenic Therapy
- Source :
- Cancers, Cancers, Vol 13, Iss 2849, p 2849 (2021), Volume 13, Issue 11
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
Abstract
- Sunitinib and pazopanib are standard first-line treatments for patients with metastatic renal cell carcinoma (mRCC). Nonetheless, as the number of treatment options increases, there is a need to identify biomarkers that can predict drug efficacy and toxicity. In this prospective study we evaluated a set of biomarkers that had been previously identified within a secretory signature in mRCC patients. This set includes tumor expression of c-Met and serum levels of HGF, IL-6, IL-8, CXCL9, CXCL10 and CXCL11. Our cohort included 60 patients with mRCC from 10 different Spanish hospitals who received sunitinib (n = 51), pazopanib (n = 4) or both (n = 5). Levels of biomarkers were studied in relation to response rate, progression-free survival (PFS) and overall survival (OS). High tumor expression of c-Met and high basal serum levels of HGF, IL-6, CXCL11 and CXCL10 were significantly associated with reduced PFS and/or OS. In multivariable Cox regression analysis, CXCL11 was identified as an independent biomarker predictive of shorter PFS and OS, and HGF was an independent predictor of reduced PFS. Correlation analyses using our cohort of patients and patients from TCGA showed that HGF levels were significantly correlated with those of IL-6, CXCL11 and CXCL10. Bioinformatic protein–protein network analysis revealed a significant interaction between these proteins, all this suggesting a coordinated expression and secretion. We also developed a prognostic index that considers this group of biomarkers, where high values in mRCC patients can predict higher risk of relapse (HR 5.28 [2.32–12.0], p &lt<br />0.0001). In conclusion, high plasma HGF, CXCL11, CXCL10 and IL-6 levels are associated with worse outcome in mRCC patients treated with sunitinib or pazopanib. Our findings also suggest that these factors may constitute a secretory cluster that acts coordinately to promote tumor growth and resistance to antiangiogenic therapy.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
renal cell carcinoma
chemokines
urologic and male genital diseases
Article
Efficacy
Pazopanib
03 medical and health sciences
Basal (phylogenetics)
0302 clinical medicine
Renal cell carcinoma
Internal medicine
Medicine
Prospective cohort study
RC254-282
business.industry
Sunitinib
Proportional hazards model
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
biomarkers
medicine.disease
cytokines
030104 developmental biology
antiangiogenic therapy
030220 oncology & carcinogenesis
Biomarker (medicine)
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 13
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....a15921d4a2e3a539e5b4b581d4e35908