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      Radiogenomics in Clear Cell Renal Cell Carcinoma: Correlations Between Advanced CT Imaging (Texture Analysis) and MicroRNAs Expression

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          Abstract

          Purpose:

          A relevant challenge for the improvement of clear cell renal cell carcinoma management could derive from the identification of novel molecular biomarkers that could greatly improve the diagnosis, prognosis, and treatment choice of these neoplasms. In this study, we investigate whether quantitative parameters obtained from computed tomography texture analysis may correlate with the expression of selected oncogenic microRNAs.

          Methods:

          In a retrospective single-center study, multiphasic computed tomography examination (with arterial, portal, and urographic phases) was performed on 20 patients with clear cell renal cell carcinoma and computed tomography texture analysis parameters such as entropy, kurtosis, skewness, mean, and standard deviation of pixel distribution were measured using multiple filter settings. These quantitative data were correlated with the expression of selected microRNAs (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both the evaluations (microRNAs and computed tomography texture analysis) were performed on matched tumor and normal corticomedullar tissues of the same patients cohort.

          Results:

          In this pilot study, we evidenced that computed tomography texture analysis has robust parameters (eg, entropy, mean, standard deviation) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression was evidenced in tumor versus normal tissue. Interestingly, entropy and miR-21-5p show promising correlation in clear cell renal cell carcinoma opening to a radiogenomic strategy to improve clear cell renal cell carcinoma management.

          Conclusion:

          In this pilot study, a promising correlation between microRNAs and computed tomography texture analysis has been found in clear cell renal cell carcinoma. A clear cell renal cell carcinoma can benefit from noninvasive evaluation of texture parameters in adjunction to biopsy results. In particular, a promising correlation between entropy and miR-21-5p was found.

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          Most cited references20

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          CT Radiogenomic Characterization of EGFR, K-RAS, and ALK Mutations in Non-Small Cell Lung Cancer.

          To assess the association between CT features and EGFR, ALK, KRAS mutations in non-small cell lung cancer.
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            Outcome prediction in patients with glioblastoma by using imaging, clinical, and genomic biomarkers: focus on the nonenhancing component of the tumor.

            To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material-enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49-1.79 years). Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features.
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              Radiogenomics of clear cell renal cell carcinoma: associations between CT imaging features and mutations.

              To investigate associations between computed tomographic (CT) features of clear cell renal cell carcinoma (RCC) and mutations in VHL, PBRM1, SETD2, KDM5C, or BAP1 genes.
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                Author and article information

                Journal
                Technol Cancer Res Treat
                Technol. Cancer Res. Treat
                TCT
                sptct
                Technology in Cancer Research & Treatment
                SAGE Publications (Sage CA: Los Angeles, CA )
                1533-0346
                1533-0338
                29 September 2019
                2019
                : 18
                : 1533033819878458
                Affiliations
                [1 ]Department of Radiological, Oncological and Pathological Sciences, University of Rome “Sapienza”—Polo Pontino, ICOT Hospital, Latina, Italy
                [2 ]Department of Radiological, Oncology and Pathology Sciences, “Sapienza” University of Rome, Italy Radiology Unit, Sant’Andrea University Hospital, Rome, Italy
                [3 ]Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, “Sapienza” University of Rome, Laboratory Affiliated With Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, Italy
                [4 ]Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Section of Anatomy, Electron Microscopy Unit, Laboratory “Pietro M. Motta,” “Sapienza” University of Rome, Rome, Italy
                [5 ]Department of Medical-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Urology Unit ICOT, Latina, Italy
                Author notes
                [*]Chiara Marigliano, Department of Radiological, Oncological and Pathological Sciences, University of Rome “Sapienza”—Polo Pontino, ICOT Hospital, Via Franco Faggiana 1668, Latina 04100, Italy. Email: chiara.marigliano@ 123456uniroma1.it
                Author information
                https://orcid.org/0000-0002-3592-4073
                https://orcid.org/0000-0001-9087-5692
                Article
                10.1177_1533033819878458
                10.1177/1533033819878458
                6767738
                31564221
                fc4cdfe4-cdb2-40e4-9dbd-8a603c8c4b4f
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 30 November 2018
                : 26 June 2019
                : 15 August 2019
                Categories
                Original Article
                Custom metadata
                January-December 2019

                texture analysis,microrna,renal cell carcinoma,radiogenomics

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