Inflammation and Immunity Gene Expression Patterns and Machine Learning Approaches in Association with Response to Immune-Checkpoint Inhibitors-Based Treatments in Clear-Cell Renal Carcinoma

Author:

Dovrolis Nikolas1ORCID,Katifelis Hector1ORCID,Grammatikaki Stamatiki1,Zakopoulou Roubini2ORCID,Bamias Aristotelis2ORCID,Karamouzis Michalis V.3ORCID,Souliotis Kyriakos45,Gazouli Maria1ORCID

Affiliation:

1. Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, 11527 Athens, Greece

2. 2nd Propaedeutic Department of Internal Medicine, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece

3. Molecular Oncology Unit, Department of Biological Chemistry, National and Kapodistrian University of Athens, 11527 Athens, Greece

4. School of Social and Education Policy, University of Peloponnese, 22100 Corinth, Greece

5. Health Policy Institute, 15123 Athens, Greece

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Despite the rapid evolution of targeted therapies, immunotherapy with checkpoint inhibition (ICI) as well as combination therapies, the cure of metastatic ccRCC (mccRCC) is infrequent, while the optimal use of the various novel agents has not been fully clarified. With the different treatment options, there is an essential need to identify biomarkers to predict therapeutic efficacy and thus optimize therapeutic approaches. This study seeks to explore the diversity in mRNA expression profiles of inflammation and immunity-related circulating genes for the development of biomarkers that could predict the effectiveness of immunotherapy-based treatments using ICIs for individuals with mccRCC. Gene mRNA expression was tested by the RT2 profiler PCR Array on a human cancer inflammation and immunity crosstalk kit and analyzed for differential gene expression along with a machine learning approach for sample classification. A number of mRNAs were found to be differentially expressed in mccRCC with a clinical benefit from treatment compared to those who progressed. Our results indicate that gene expression can classify these samples with high accuracy and specificity.

Funder

European Union’s Horizon 2020 research and innovation program

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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