A CT-Based Radiomics Approach for the Differential Diagnosis of Sarcomatoid and Clear Cell Renal Cell Carcinoma

This study was aimed at building a computed tomography- (CT-) based radiomics approach for the differentiation of sarcomatoid renal cell carcinoma (SRCC) and clear cell renal cell carcinoma (CCRCC). It involved 29 SRCC and 99 CCRCC patient cases, and to each case, 1029 features were collected from each of the corticomedullary phase (CMP) and nephrographic phase (NP) image. Then, features were selected by using the least absolute shrinkage and selection operator regression method and the selected features of the two phases were explored to build three radiomics approaches for SRCC and CCRCC classification. Meanwhile, subjective CT findings were filtered by univariate analysis to construct a radiomics model and further selected by Akaike information criterion for integrating with the selected image features to build the fifth model. Finally, the radiomics models utilized the multivariate logistic regression method for classification and the performance was assessed with receiver operating characteristic curve (ROC) and DeLong test. The radiomics models based on the CMP, the NP, the CMP and NP, the subjective findings, and the combined features achieved the AUC (area under the curve) value of 0.772, 0.938, 0.966, 0.792, and 0.974, respectively. Significant difference was found in AUC values between each of the CMP radiomics model (0.0001≤p≤0.0051) and the subjective findings model (0.0006≤p≤0.0079) and each of the NP radiomics model, the CMP and NP radiomics model, and the combined model. Sarcomatoid change is a common pathway of dedifferentiation likely occurring in all subtypes of renal cell carcinoma, and the CT-based radiomics approaches in this study show the potential for SRCC from CCRCC differentiation.

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A Risk Assessment Model of Immune-Associated lncRNA to Predict the Prognosis and Immune Landscape of Renal Clear Cell Carcinoma

10.21203/rs.3.rs-944336/v1 ◽

2021 ◽

Author(s):

Tiantian Ma ◽

Cuiwen Zhu ◽

Yiping Duan ◽

Lingyue Chen ◽

Jiacui Liu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Characteristic Curve ◽

Univariate Analysis ◽

Risk Groups ◽

Renal Clear Cell Carcinoma ◽

Assessment Model ◽

Cell Renal Cell Carcinoma

Abstract Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary system, accounting for 3% of adult malignancies. Long non-coding RNA (lncRNA) is abnormally regulated in many cancers and can be used as a molecular marker for early diagnosis and prognosis of RCC. Here, original lncRNA datas were retrieved from TCGA, differential co-expression analysis was performed to classify immune-related lncRNA (irlncRNA) with differential expression, and the improved 0 or 1 matrix cyclic single pairing method was used to verify lncRNA pairs. Then, we performed a univariate analysis in combination with an improved Lasso penalty regression that included cross-validation, multiple repetitions, and random stimulus procedures to determine different expression irlncRNA (DEirlncRNA) pairs. AUC values under Receiver Operating Characteristic curve (ROC) were calculated to obtain the optimal model, and AIC values of each point on AUC were calculated to obtain the optimal cut-off point to distinguish the high and low risk groups of Clear-cell renal cell carcinoma (ccRCC) patients. Finally, we evaluated the new model in a variety of clinical settings including survival, clinicopathological features, tumor-infiltrating immune cells, chemotherapy, and checkpoint related biomarkers, all showing promising clinical application.

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Integrative analysis of cross-modal features for the prognosis prediction of clear cell renal cell carcinoma

Bioinformatics ◽

10.1093/bioinformatics/btaa056 ◽

2020 ◽

Vol 36 (9) ◽

pp. 2888-2895 ◽

Cited By ~ 1

Author(s):

Zhenyuan Ning ◽

Weihao Pan ◽

Yuting Chen ◽

Qing Xiao ◽

Xinsen Zhang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Genomic Data ◽

Image Features ◽

Cell Renal Cell Carcinoma ◽

Multimodal Data ◽

Integrative Framework ◽

Deep Image

Abstract Motivation As a highly heterogeneous disease, clear cell renal cell carcinoma (ccRCC) has quite variable clinical behaviors. The prognostic biomarkers play a crucial role in stratifying patients suffering from ccRCC to avoid over- and under-treatment. Researches based on hand-crafted features and single-modal data have been widely conducted to predict the prognosis of ccRCC. However, these experience-dependent methods, neglecting the synergy among multimodal data, have limited capacity to perform accurate prediction. Inspired by complementary information among multimodal data and the successful application of convolutional neural networks (CNNs) in medical image analysis, a novel framework was proposed to improve prediction performance. Results We proposed a cross-modal feature-based integrative framework, in which deep features extracted from computed tomography/histopathological images by using CNNs were combined with eigengenes generated from functional genomic data, to construct a prognostic model for ccRCC. Results showed that our proposed model can stratify high- and low-risk subgroups with significant difference (P-value < 0.05) and outperform the predictive performance of those models based on single-modality features in the independent testing cohort [C-index, 0.808 (0.728–0.888)]. In addition, we also explored the relationship between deep image features and eigengenes, and make an attempt to explain deep image features from the view of genomic data. Notably, the integrative framework is available to the task of prognosis prediction of other cancer with matched multimodal data. Availability and implementation https://github.com/zhang-de-lab/zhang-lab? from=singlemessage Supplementary information Supplementary data are available at Bioinformatics online.

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Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma

PeerJ ◽

10.7717/peerj.11901 ◽

2021 ◽

Vol 9 ◽

pp. e11901

Author(s):

Na Li ◽

Jie Chen ◽

Qiang Liu ◽

Hongyi Qu ◽

Xiaoqing Yang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Univariate Analysis ◽

Prognostic Significance ◽

Clinical Role ◽

Cell Renal Cell Carcinoma ◽

Cancer Specific Survival ◽

Immune Infiltration

Mammalian target of rapamycin (mTOR), a serine/threonine kinase involved in cell proliferation, survival, metabolism and immunity, was reportedly activated in various cancers. However, the clinical role of mTOR in renal cell carcinoma (RCC) is controversial. Here we detected the expression and prognosis of total mTOR and phosphorylated mTOR (p-mTOR) in clear cell RCC (ccRCC) patients, and explored the interactions between mTOR and immune infiltrates in ccRCC. The protein level of mTOR and p-mTOR was determined by western blotting (WB), and their expression was evaluated in 145 ccRCC and 13 non-tumor specimens by immunohistochemistry (IHC). The relationship to immune infiltration of mTOR was further investigated using TIMER and TISIDB databases, respectively. WB demonstrated the ratio of p-mTOR to mTOR was higher in ccRCC than adjacent specimens (n = 3), and IHC analysis elucidated that p-mTOR expression was positively correlated with tumor size, stage and metastasis status, and negatively correlated with cancer-specific survival (CSS). In univariate analysis, high grade, large tumor, advanced stage, metastasis, and high p-mTOR expression were recognized as prognostic factors of poorer CSS, and multivariate survival analysis elucidated that tumor stage, p-mTOR and metastasis were of prognostic value for CSS in ccRCC patients. Further TIMER and TISIDB analyses uncovered that mTOR gene expression was significantly associated with numerous immune cells and immunoinhibitors in patients with ccRCC. Collectively, these findings revealed p-mTOR was identified as an independent predictor of poor survival, and mTOR was associated with tumor immune infiltrates in ccRCC patients, which validated mTOR could be implicated in the initiation and progression of ccRCC.

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Genomic Analysis Reveals Novel Specific Metastatic Mutations in Chinese Clear Cell Renal Cell Carcinoma

BioMed Research International ◽

10.1155/2020/2495157 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Hui Meng ◽

Xuewen Jiang ◽

Jianfeng Cui ◽

Gang Yin ◽

Benkang Shi ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Genomic Analysis ◽

Renal Clear Cell Carcinoma ◽

Genomic Feature ◽

Cell Renal Cell Carcinoma ◽

Hybridization Capture ◽

Significant Difference

Clear cell renal cell carcinoma (ccRCC) accounts for more than 75% of renal cell carcinoma. Nearly 25% of ccRCC patients were diagnosed with metastasis. Though the genomic profile of ccRCC has been widely studied, the difference between localized and metastatic ccRCC was not clarified. Primary tumor samples and matched whole blood were collected from 106 sporadic patients diagnosed with renal clear cell carcinoma at Qilu Hospital of Shandong University from January 2017 to November 2019, and 17 of them were diagnosed with metastasis. A hybridization capture-based next-generation sequencing of 618 cancer-related genes was performed to investigate the somatic and germline variants, tumor mutation burden (TMB), and microsatellite instability (MSI). Five genes with significantly different prevalence were identified in the metastatic group, especially TOP1 (17.65% vs. 0%) and SNCAIP (17.65% vs. 0%). The altered frequency of PBRM1 (0% vs. 27%) and BAP1 (24% vs. 10%) differed between the metastatic and nonmetastatic groups, which may relate to the prognosis. Of these 106 patients, 42 patients (39.62%) had at least one alteration in DNA damage repair (DDR) genes, including 58.82% of metastatic ccRCC patients and 35.96% of ccRCC patients without metastasis. Ten pathogenic or likely pathogenic (P/LP) variants were identified in 11 sporadic clear cell renal cell carcinoma patients (10.38%), including rarely reported ATM (n=1), MUTYH (n=1), NBN (n=1), RAD51D (n=1), and BRCA2 (n=1). No significant difference in the ratio of P/LP variant carriers or TMB was identified between the metastatic and nonmetastatic groups. We found a unique genomic feature of Chinese metastatic ccRCC patients with a higher prevalence of alterations in DDR, TOP1, and SNCAIP. Further investigated studies and drug development are needed in the future.

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Visceral Adiposity as a Significant Predictor of Sunitinib-Induced Dose-Limiting Toxicities and Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma

Cancers ◽

10.3390/cancers12123602 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3602

Author(s):

Jee Soo Park ◽

Kyo Chul Koo ◽

Doo Yong Chung ◽

Sun Il Kim ◽

Jeongho Kim ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Body Composition ◽

Adipose Tissue ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Univariate Analysis ◽

Progression Free Survival ◽

Visceral Adiposity ◽

Cell Renal Cell Carcinoma

Sunitinib is a first-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about the predictive factors of sunitinib-induced dose-limiting toxicity (DLT) in Asian populations. We investigated whether body composition predicts sunitinib-induced DLT. We retrospectively reviewed sunitinib-treated Korean patients with clear cell mRCC from eight institutions. Body composition was measured using computed tomography. DLT was defined as any adverse event leading to dose reduction or treatment discontinuation. Univariate analysis was used to compare body composition indices, and logistic regression analyses were performed for factors predicting early DLT. Overall, 111/311 (32.5%) of patients experienced DLT. Significant differences were observed in the subcutaneous adipose tissue index (SATI; p = 0.001) and visceral adipose tissue index (VATI; p < 0.001) between patients with and without DLT. Multivariate analyses revealed that VATI (odds ratio: 1.013; p = 0.029) was significantly associated with early DLT. Additionally, 20% of patients who had a body mass index (BMI) greater than 23 kg/m2 and a low VATI experienced DLT, whereas 34.3% of the remaining groups had DLT (p = 0.034). Significant differences were observed for median progression-free survival (13.0 vs. 26.0 months, respectively; p = 0.006) between patients with low and high VATI. Visceral adiposity was a significant predictor of sunitinib-associated DLT and survival. Patients with a low VATI and a BMI greater than 23 kg/m2 experienced lower DLTs.

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Subcutaneous Adipose Tissue Reduction in Patients with Clear Cell Renal Cell Carcinoma and Peritumoral Collateral Vessels: A Retrospective Observational Study

Applied Sciences ◽

10.3390/app11136076 ◽

2021 ◽

Vol 11 (13) ◽

pp. 6076

Author(s):

Federico Greco ◽

Luigi Giuseppe Quarta ◽

Aldo Carnevale ◽

Melchiore Giganti ◽

Rosario Francesco Grasso ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Adipose Tissue ◽

Cell Carcinoma ◽

Renal Cell ◽

Subcutaneous Adipose Tissue ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Significant Difference ◽

Collateral Vessels ◽

Subcutaneous Adipose

Background: peritumoral collateral vessels adjacent to renal cell carcinoma (RCC) can be encountered in clinical practice. Cancer cachexia is defined as a decrease of adipose and skeletal muscle tissues. In this study we evaluated, using a quantitative CT imaging-based approach, the distribution of abdominal adipose tissue in clear cell RCC (ccRCC) male patients with and without collateral vessels. Methods: between November 2019 and February 2020, in this retrospective study we enrolled 106 ccRCC male Caucasian patients divided into two groups: a ccRCCa group without collateral vessels (n = 48) and a ccRCCp group with collateral vessels (n = 58). The total adipose tissue (TAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured in both groups. Moreover, the VAT/SAT ratio was calculated for each subject. Results: a statistically significant difference between the two groups was found in the SAT area (p < 0.05), while no significant differences were found in the TAT area, VAT area and VAT/SAT ratio. Conclusion: this study demonstrates a reduction of SAT in ccRCC patients with peritumoral collateral vessels.

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Analyzing and validating the prognostic value and immune microenvironment of clear cell renal cell carcinoma

10.21203/rs.3.rs-274762/v1 ◽

2021 ◽

Author(s):

Jingwei Ke ◽

Jie Chen ◽

Xin Liu

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clinical Characteristics ◽

Cox Regression ◽

Clear Cell ◽

Gene Set Enrichment Analysis ◽

Hub Genes ◽

Cell Renal Cell Carcinoma ◽

Significant Difference

Abstract Background: There is still controversy regarding immunotherapy biomarkers. Therefore, we aimed to identify prognostic biomarkers related to immunotherapy for clear cell renal cell carcinoma (ccRCC).Methods: Fragments Per Kilobase Million (FPKM) data and clinical characteristics for ccRCC patients from The Cancer Genome Atlas (TCGA) database were downloaded. Unsupervised consensus clustering analysis was performed to divide patients into different immune subgroups according to their single-sample gene set enrichment analysis (ssGSEA) scores. Then, we validated the differences in immune cell infiltration, prognosis, clinical characteristics and expression levels of HLA and immune checkpoint genes between different immune subgroups. Weighted gene coexpression network analysis (WGCNA) was used to identify the significant modules and hub genes that were related to the immune subgroups. A nomogram was established to predict the overall survival (OS) outcomes after independent prognostic factors were identified by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses.Results: Five clusters (immune subgroups) were identified. There was no significant difference in age, sex or N stage. And there were significant differences in race, T stage, M stage, grade, prognosis and tumor microenvironment. HLA gene families and CTLA4 showed significant differences between the five clusters, while PD1 and PDL1 did not. The red module was significant, and 14 hub genes were obtained. In addition, the nomogram containing LAG3 and GZMK accurately predicted OS outcomes of ccRCC patients.Conclusion: LAG3 and GZMK are strongly related to immunity and may provide suggestions for ccRCC immunotherapy.

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Prospective assessment of circulating endothelial cells (CECs) as early markers of clear cell renal cell carcinoma (CCRCC) progression in first-line setting: The Circles study (SOGUG 2011-01).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.436 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 436-436

Author(s):

Victor Oyarvides ◽

Daniel Castellano ◽

Luis Leon Mateos ◽

Emilio Esteban ◽

Laura Basterretxea ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Endothelial Cells ◽

Tumor Progression ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Circulating Endothelial Cells ◽

First Line ◽

Cell Renal Cell Carcinoma ◽

Significant Difference

436 Background: Angiogenesis inhibitors have become a cornerstone in the management of clear cell renal cell carcinoma (CCRCC). Since circulating endothelial cells (CECs) counts have been proposed as surrogate biomarkers of angiogenesis, they could potentially be used to assess the activity of such drugs. Methods: An observational prospective study is being performed in 11 institutions members of the SOGUG group. Patients with confirmed CCRCC on first-line treatment who have not progressed after 3 months of therapy are considered eligible. CECs (CD 105+,CD 45-, DAPI + cells assessed by the Cell Search system), are determined every 6 weeks for 15 months or radiological tumor progression. Results: Up to 64 of the 75 scheduled patients have already been recruited. Mean age was 64 years, 73% were men and 27% women. Distribution upon MSKCC risk cathegories was: good 30%, intermediate 58%, poor 3% and not available (N/A) 9%. 57 (90%) patients received sunitinib, 3 (5%) pazopanib, 1 (2%) temsirolimus and was N/A in 3 (5%). The CECs counts were determined in 60 patients. At baseline median was 47 cells/4 ml (range 4-480). When comparing patients who experienced tumor progression while on study (11 cases) with patients who did not (28 CECs/4 ml vs. 73 CECs/4ml respectively), a significant difference was found (p = 0.002, t-student). Several exploratory analysis regarding concomitant conditions and patients and tumor characteristics showed that cases with heavily treated hypertension (8 in 60 patients) had lower baseline CECs counts, though without statistical significance (p = 0.068, t-student). Conclusions: Our data point to a different behaviour of CECs counts among CCRCC patients tretated with anitangiogenic drugs that could lead to identify specific subpopulations. Mature results will be presented at the meeting.

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Metastasis-associated mutations in clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.600 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 600-600

Author(s):

Banumathy Gowrishankar ◽

Manickam Janakiraman ◽

Chung-Han Lee ◽

Venkata Jaganmohan Thodima ◽

Ana M. Molina ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Stage I ◽

Cell Renal Cell Carcinoma ◽

Initial Finding ◽

Therapeutic Implications ◽

Synonymous Mutations ◽

Significant Difference

600 Background: Over 30% of patients with clear cell renal cell carcinoma (ccRCC) exhibit metastasis at the time of diagnosis and exhibit poor outcome. About 20-50% of patients with localized disease eventually develop metastasis after nephrectomy. The goal of the current study was to identify target gene mutations associated with ccRCC metastasis. Methods: In this IRB approved study, genomic DNA from 128 ccRCC resected specimens (128 unique patients) were profiled using a custom targeted next-generation sequencing (NGS) panel comprising 70 frequently mutated genes and prognostic SNPs in renal cancer. The specimen cohort consisted of 78 primary (29 stage I-III, 30 stage IV, 19 unknown) and 50 metastatic (10 lung, 9 bone, 25 other sites, 6 unknown) lesions. Following hybrid capture, sequencing was performed (MiSeq, Illumina) and variants identified using CLCbio (Qiagen). Chi-square test was used to test for significance. Results: The median specimen had 4 non-synonymous mutations (123/128 samples had at least one mutation). 66 genes showed a non-synonymous mutation in at least one specimen. There was no significant difference between total mutation count between primary and metastatic specimens (Mann-Whitney test). TSC1 mutation was significantly enriched in metastatic (8/50) compared with primary lesions (3/78). No TSC1 mutation was found in the 29 localized (stage I-III) primary lesions. Interestingly, TSC1 maps to 9q34 and our prior copy number studies indicated that loss of 9q is also enriched in metastatic lesions. Of the 11 specimens bearing TSC1 mutation in this cohort, 5 also had loss of 9q. In 44 specimens with known sites of resection, SETD2 and TSC1 mutations were not found in metastases to the lung but found in 30-40% of lesions at other sites, KDM5C and TSC1 mutations were not found in metastases to the bone while 25-30% of lesions at other sites exhibited these mutations. Due to the limited sample size, significance could not be determined for these associations. Conclusions: Preliminary results of this study implicated TSC1 in the metastasis of ccRCC. Since TSC1 mutation is known to confer sensitivity to mTOR inhibitors, our initial finding of absence of TSC1 mutation in lung and bone sites of metastasis may have therapeutic implications.

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Preoperative Butyrylcholinesterase Level as an Independent Predictor of Overall Survival in Clear Cell Renal Cell Carcinoma Patients Treated with Nephrectomy

The Scientific World JOURNAL ◽

10.1155/2014/948305 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Takuya Koie ◽

Chikara Ohyama ◽

Jotaro Mikami ◽

Hiromichi Iwamura ◽

Naoki Fujita ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Distant Metastasis ◽

Renal Cell ◽

Clear Cell ◽

Independent Predictor ◽

Univariate Analysis ◽

Prognostic Significance ◽

Cell Renal Cell Carcinoma

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168–470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%,P=0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients.

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