Abstract 1397: Quantitative MR imaging measures predict intratumoral molecular heterogeneity in clear cell renal cell carcinoma

2019 ◽  
Author(s):  
Durga Udayakumar ◽  
Ze Zhang ◽  
Durgesh Dwivedi ◽  
Yin Xi ◽  
Tao Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mr Imaging ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Molecular Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Quantitative Mr Imaging ◽  
Quantitative Mr

Intratumoural heterogeneity may hinder precision medicine strategies in patients with clear cell renal cell carcinoma

2018 ◽  
Vol 71 (5) ◽  
pp. 467-471 ◽  
Author(s):  
Maria Rosaria Raspollini ◽  
Ilaria Montagnani ◽  
Rodolfo Montironi ◽  
Francesca Castiglione ◽  
Guido Martignoni ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Precision Medicine ◽  
Renal Cell ◽  
Clear Cell ◽  
Molecular Heterogeneity ◽  
Precision Oncology ◽  
Cell Renal Cell Carcinoma ◽  
Renal Sinus ◽  
The Moment

Clear cell renal cell carcinoma (ccRCC) is an heterogeneous tumour at architectural, cellular and molecular level, a reason why the 2014 International Society of Urological Pathology consensus recommended wide sampling of RCC masses to include at least 1 block/cm of tumour together with perpendicular sections of the tumour/perinephric fat interface and the tumour/renal sinus interface. Intratumoural molecular heterogeneity may be a limitation at the moment of defining precision medicine strategies based on gene mutation status. This study analyses the presence of any mutation of KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR genes in 20 tissue blocks from a case of ccRCC and its metastasis. We observed the presence of the mutation at pH1047R of PIK3CA gene in five samples of the tumour, while the remaining 15 samples did not show any mutation at PIK3CA or any other investigated gene. There is a great need to develop novel RCC sampling strategies to overcome tumour heterogeneity prior to define precision oncology strategies.

Dynamic contrast-enhanced MRI to predict intratumoral molecular heterogeneity in clear cell renal cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4580-4580
Author(s):  
Durga Udayakumar ◽  
Ze Zhang ◽  
Durgesh Dwivedi ◽  
Yin Xi ◽  
Tao Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Molecular Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Post Contrast ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

4580 Background: Mutation/inactivation of VHL in clear cell renal cell carcinoma (ccRCC) leads to upregulation of hypoxia inducible factors ( HIFs) and angiogenesis. However, ccRCC is characterized by high intra-tumor heterogeneity (ITH). Random small samples such as those in percutaneous biopsies are likely limited for characterization of molecular alterations in heterogeneous ccRCCs. We hypothesize that whole-tumor dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is useful to noninvasively identify ITH in ccRCC. Methods: This IRB-approved, prospective, HIPAA-compliant study, included 62 ccRCCs. 3T DCE MRI was obtained prior to nephrectomy. Surgical specimens were sectioned to match MRI acquisition plane. 182 snap frozen samples (49 tumors) and adjacent uninvolved renal parenchyma (URP) were collected. RNA isolations, cDNA library preparation and mRNA sequencing were performed using standard protocols. RNA expression in 81 tumor samples were correlated (Spearman ranked) with % enhancement in a region of interest (ROI) drawn in the same location of the tumor on pre- and 3 different post-contrast DCE MRI phases. Gene function overrepresentation (OR) analyses were done on top positively and negatively correlated genes. False discovery rate (FDR) < 0.1 was considered statistically significant. Results: Principal component analysis of > 20,000 genes indicated distinct gene expression in tumors from URP. Unsupervised clustering showed enrichment of ccA samples (better prognosis) compared to ccB samples (worse prognosis). Importantly, ccA and ccB samples coexisted in 25% of tumors. DCE-MRI % enhancement correlated with expression of > 300 genes (p < 0.003, FDR < 0.1). OR analyses placed angiogenic pathway gene processes and the immune/inflammatory response processes within the top 5 positively- and negatively-correlated gene functions, respectively. HIF2 target genes correlated positively with % enhancement. Conclusions: DCE MRI detects specific molecular signatures and may help overcome the challenges of ITH in ccRCC. Further research is needed to explore the potential role of DCE MRI to assess response to antiangiogenic and immune-based therapies.

scholarly journals Deciphering Intratumoral Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma with a Radiogenomics Platform

2021 ◽  
pp. clincanres.0706.2021
Author(s):  
Durga Udayakumar ◽  
Ze Zhang ◽  
Yin Xi ◽  
Durgesh K. Dwivedi ◽  
Michael Fulkerson ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Molecular Heterogeneity ◽  
Cell Renal Cell Carcinoma

Metastatic adrenal tumor from clear-cell renal cell carcinoma: a pitfall of chemical shift MR imaging

2001 ◽  
Vol 26 (4) ◽  
pp. 439-442 ◽  
Author(s):  
K. Shinozaki ◽  
K. Yoshimitsu ◽  
H. Honda ◽  
T. Kuroiwa ◽  
H. Irie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Chemical Shift ◽  
Mr Imaging ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Adrenal Tumor ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Establishment of a prognosis Prediction Model Based on Pyroptosis-Related Signatures Associated With the Immune Microenvironment and Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Aimin Jiang ◽  
Jialin Meng ◽  
Yewei Bao ◽  
Anbang Wang ◽  
Wenliang Gong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prediction Model ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Molecular Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Prognosis Prediction ◽  
Model Based ◽  
Prognosis Prediction Model

BackgroundPyroptosis is essential for tumorigenesis and progression of neoplasm. However, the heterogeneity of pyroptosis and its relationship with the tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC) remain unclear. The purpose of the present study was to identify pyroptosis-related subtypes and construct a prognosis prediction model based on pyroptosis signatures.MethodsFirst, heterogenous pyroptosis subgroups were explored based on 33 pyroptosis-related genes and ccRCC samples from TCGA, and the model established by LASSO regression was verified by the ICGC database. Then, the clinical significance, functional status, immune infiltration, cell–cell communication, genomic alteration, and drug sensitivity of different subgroups were further analyzed. Finally, the LASSO-Cox algorithm was applied to narrow down the candidate genes to develop a robust and concise prognostic model.ResultsTwo heterogenous pyroptosis subgroups were identified: pyroptosis-low immunity-low C1 subtype and pyroptosis-high immunity-high C2 subtype. Compared with C1, C2 was associated with a higher clinical stage or grade and a worse prognosis. More immune cell infiltration was observed in C2 than that in C1, while the response rate in the C2 subgroup was lower than that in the C1 subgroup. Pyroptosis-related genes were mainly expressed in myeloid cells, and T cells and epithelial cells might influence other cell clusters via the pyroptosis-related pathway. In addition, C1 was characterized by MTOR and ATM mutation, while the characteristics of C2 were alterations in SPEN and ROS1 mutation. Finally, a robust and promising pyroptosis-related prediction model for ccRCC was constructed and validated.ConclusionTwo heterogeneous pyroptosis subtypes were identified and compared in multiple omics levels, and five pyroptosis-related signatures were applied to establish a prognosis prediction model. Our findings may help better understand the role of pyroptosis in ccRCC progression and provide a new perspective in the management of ccRCC patients.

scholarly journals Characterization of Molecular Heterogeneity Associated With Tumor Microenvironment in Clear Cell Renal Cell Carcinoma to Aid Immunotherapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Weimin Zhong ◽  
Yinan Li ◽  
Yichu Yuan ◽  
Hongbin Zhong ◽  
Chaoqun Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Personalized Treatment ◽  
Validation Dataset ◽  
Molecular Heterogeneity ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and has strong immunogenicity. A systematically investigation of the tumor microenvironment (TME) in ccRCC could contribute to help clinicians develop personalized treatment and facilitate clinical decision-making. In this study, we analyzed the immune-related subtype of ccRCC on the basis of immune-related gene expression data in The Cancer Genome Atlas (TCGA, N = 512) and E-MTAB-1980 (N = 101) dataset, respectively. As a result, two subtypes (C1 and C2) were identified by performing non-negative matrix factorization clustering. Subtype C1 was characterized by increased advance ccRCC cases and immune-related pathways. A higher immune score, stromal score, TMB value, Tumor Immune Dysfunction and Exclusion (TIDE) prediction score, and immune checkpoint genes expression level were also observed in C1. In addition, the C1 subtype might benefit from chemotherapy and immunotherapy. The patients in subtype C2 had more metabolism-related pathways, higher tumor purity, and a better prognosis. Moreover, some small molecular compounds for the treatment of ccRCC were identified between the two subtypes by using the Connectivity Map (CMap) database. Finally, we constructed and validated an immune-related (IR) score to evaluate immune modification individually. A high IR score corresponded to a favorable prognosis compared to a low IR score, while more advanced tumor stage and grade cases were enriched in the low IR score group. The two IR score groups also showed a distinct divergence among immune status, TME, and chemotherapy. The external validation dataset (E-MTAB-1980) and another immunotherapy cohort (IMvigor 210) demonstrated that patients in the high IR score group had a significantly prolonged survival time and clinical benefits compared to the low IR score group. Together, characterization of molecular heterogeneity and IR signature may help develop new insights into the TME of ccRCC and provide new strategies for personalized treatment.

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