دورية أكاديمية
Deciphering Intratumoral Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma with a Radiogenomics Platform.
| العنوان: | Deciphering Intratumoral Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma with a Radiogenomics Platform. |
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| المؤلفون: | Udayakumar D; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas.; Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas.; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas., Zhang Z; Quantitative Biomedical Research Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas., Xi Y; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas.; Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas., Dwivedi DK; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., Fulkerson M; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., Haldeman S; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., McKenzie T; Department of Pathology, UT Southwestern Medical Center, Dallas, Texas., Yousuf Q; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas., Joyce A; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas., Hajibeigi A; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., Notgrass H; Department of Pathology, UT Southwestern Medical Center, Dallas, Texas., de Leon AD; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., Yuan Q; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., Lewis MA; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., Madhuranthakam AJ; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas.; Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas., Sibley RC; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., Elias R; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas., Guo J; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas., Christie A; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas., McKay RM; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas., Cadeddu JA; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas.; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Urology, UT Southwestern Medical Center, Dallas, Texas., Bagrodia A; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Urology, UT Southwestern Medical Center, Dallas, Texas., Margulis V; Department of Urology, UT Southwestern Medical Center, Dallas, Texas.; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia., Brugarolas J; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas., Wang T; Quantitative Biomedical Research Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas.; Center for the Genetics of Host Defense, UT Southwestern Medical Center, Dallas, Texas., Kapur P; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.; Department of Urology, UT Southwestern Medical Center, Dallas, Texas., Pedrosa I; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas. Ivan.Pedrosa@UTSouthwestern.edu.; Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas.; Kidney Cancer Program - Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.; Department of Urology, UT Southwestern Medical Center, Dallas, Texas. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Sep 01; Vol. 27 (17), pp. 4794-4806. Date of Electronic Publication: 2021 Jul 01. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Radiation Genomics* , Tumor Microenvironment*, Carcinoma, Renal Cell/*diagnostic imaging , Carcinoma, Renal Cell/*genetics , Carcinoma, Renal Cell/*pathology , Kidney Neoplasms/*diagnostic imaging , Kidney Neoplasms/*genetics , Kidney Neoplasms/*pathology , Magnetic Resonance Imaging/*methods, Adult ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use ; Carcinoma, Renal Cell/drug therapy ; Female ; Humans ; Kidney Neoplasms/drug therapy ; Male ; Middle Aged ; Prospective Studies |
| مستخلص: | Purpose: Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell carcinoma (ccRCC) and is a confounding factor for therapy selection. Most approaches to evaluate ITH are limited by two-dimensional ex vivo tissue analyses. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can noninvasively assess the spatial landscape of entire tumors in their natural milieu. To assess the potential of DCE-MRI, we developed a vertically integrated radiogenomics colocalization approach for multi-region tissue acquisition and analyses. We investigated the potential of spatial imaging features to predict molecular subtypes using histopathologic and transcriptome correlatives. Experimental Design: We report the results of a prospective study of 49 patients with ccRCC who underwent DCE-MRI prior to nephrectomy. Surgical specimens were sectioned to match the MRI acquisition plane. RNA sequencing data from multi-region tumor sampling (80 samples) were correlated with percent enhancement on DCE-MRI in spatially colocalized regions of the tumor. Independently, we evaluated clinical applicability of our findings in 19 patients with metastatic RCC (39 metastases) treated with first-line antiangiogenic drugs or checkpoint inhibitors. Results: DCE-MRI identified tumor features associated with angiogenesis and inflammation, which differed within and across tumors, and likely contribute to the efficacy of antiangiogenic drugs and immunotherapies. Our vertically integrated analyses show that angiogenesis and inflammation frequently coexist and spatially anti-correlate in the same tumor. Furthermore, MRI contrast enhancement identifies phenotypes with better response to antiangiogenic therapy among patients with metastatic RCC. Conclusions: These findings have important implications for decision models based on biopsy samples and highlight the potential of more comprehensive imaging-based approaches. (©2021 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | R01 CA154475 United States CA NCI NIH HHS; P30 CA142543 United States CA NCI NIH HHS; P50 CA196516 United States CA NCI NIH HHS; U01 CA207091 United States CA NCI NIH HHS; R01 CA258584 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Angiogenesis Inhibitors) |
| تواريخ الأحداث: | Date Created: 20210702 Date Completed: 20220404 Latest Revision: 20220404 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8493519 |
| DOI: | 10.1158/1078-0432.CCR-21-0706 |
| PMID: | 34210685 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
|---|---|
| DOI: | 10.1158/1078-0432.CCR-21-0706 |