scholarly journals Prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC)

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiu Zhengqi ◽  
Guo Zezhi ◽  
Jiang Lei ◽  
Qiu He ◽  
Pan Jinyao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cox Regression ◽  
Clear Cell ◽  
Regression Analyses ◽  
Prognostic Role ◽  
Pyruvate Metabolism ◽  
Cell Renal Cell Carcinoma ◽  
Pathologic Features

AbstractThis study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analyzed by univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene–gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e−19). Kaplan–Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e−05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p = 0.025), high stage (StageIII & IV, p = 5.604e−05), and high level of stage_T (T3-4, p = 4.373e−05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p < 0.05). Nomogram including clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway, and renin–angiotensin system were differentially enriched in PHYH high-expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p < 0.05). We suspect that elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism, and RAS might be the key pathways regulated by PHYH in CCRC.

scholarly journals Prognostic role of PHYH for Overall Survival (OS) in clear cell Renal Cell Carcinoma (ccRCC)

2020 ◽  
Author(s):  
Zhengqi Qiu ◽  
Guo Zezhi ◽  
Jiang Lei ◽  
Qiu He ◽  
Pan Jinyao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cox Regression ◽  
Clear Cell ◽  
Regression Analyses ◽  
Prognostic Role ◽  
Pyruvate Metabolism ◽  
Cell Renal Cell Carcinoma ◽  
Pathologic Features

Abstract This study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analysed by Univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene-gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e-19). Kaplan-Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e-05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p=0.025), high stage (StageIII & IV, p=5.604e-05), High level of stage_T (T3-4, p=4.373e-05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p<0.05). Nomogram including Clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway and Renin angiotensin system were differentially enriched in PHYH high expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p<0.05). We suspect that Elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism and RAS might be the key pathways regulated by PHYH in CCRC.

scholarly journals A novel 10 glycolysis-related genes signature could predict overall survival for clear cell renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qianwei Xing ◽  
Tengyue Zeng ◽  
Shouyong Liu ◽  
Hong Cheng ◽  
Limin Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract Background The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Methods Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. Results Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. Conclusions A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival.

1999 PROGNOSTIC ROLE OF TUMOR NECROSIS IN CLEAR CELL RENAL CELL CARCINOMA: RESULTS OF THE SATURN PROJECT

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
C. Valotto ◽  
G. Novara ◽  
A. Antonelli ◽  
G. Carmignani ◽  
S. Cosciani Cunico ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Necrosis ◽  
Clear Cell ◽  
Prognostic Role ◽  
Cell Renal Cell Carcinoma

scholarly journals Prognostic role of preoperative albumin to globulin ratio in predicting survival of clear cell renal cell carcinoma

2018 ◽  
Vol 44 (5) ◽  
pp. 933-946 ◽  
Author(s):  
Murat Yavuz Koparal ◽  
Fazlı Polat ◽  
Serhat Çetin ◽  
Ender Cem Bulut ◽  
Tevfik Sinan Sözen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Prognostic Role ◽  
Cell Renal Cell Carcinoma ◽  
Preoperative Albumin ◽  
Albumin To Globulin Ratio

scholarly journals Prognostic role of S100A9 expression in patients with clear cell renal cell carcinoma

Medicine ◽  
2019 ◽  
Vol 98 (40) ◽  
pp. e17188
Author(s):  
Hyun Min Koh ◽  
Hyo Jung An ◽  
Gyung Hyuck Ko ◽  
Jeong Hee Lee ◽  
Jong Sil Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Prognostic Role ◽  
Cell Renal Cell Carcinoma ◽  
S100a9 Expression

scholarly journals Bim Expression in Peritumoral Lymphocytes is Associated with Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma

Kidney Cancer ◽  
2021 ◽  
pp. 1-7
Author(s):  
Bimal Bhindi ◽  
Elizabeth Bearrick ◽  
John C. Cheville ◽  
Christine M. Lohse ◽  
Ross J. Mason ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Immunohistochemistry Staining ◽  
Multivariable Adjustment

Background: Bim (BCL-2-interacting mediator of cell death) is a downstream pro-apoptotic signaling molecule activated by the PD-1 pathway. Objective: We sought to determine if Bim expression in peritumoral T-lymphocytes (PTLs) is associated with survival in patients with metastatic clear cell renal cell carcinoma (ccRCC). Methods: Immunohistochemistry staining for Bim was performed on paraffin-embedded tumor tissue blocks from patients with metastatic ccRCC who underwent nephrectomy between 1990-2004. Associations of Bim expression with cancer-specific survival (CSS) and overall survival (OS) from date of metastasis were evaluated using multivariable Cox regression models, adjusting for age, sex, and metastases-score. Results: 525 patients with metastatic ccRCC, of whom 169 (32%) had metastases at time of nephrectomy were studied. After multivariable adjustment, high Bim expression remained associated with worse CSS (HR = 1.31; 95%CI 1.07–1.59; p = 0.008) and OS (HR = 1.28; 95%CI 1.06–1.55; p = 0.01). The interaction between Bim and PD-L1 was not statistically significant for CSS (p = 0.68) or OS (p = 0.57), suggesting that the associations between Bim and survival outcomes were not significantly different based on tumor PD-L1 expression. Conclusion: High Bim expression in PTLs at nephrectomy is prognostic of worse CSS and OS in patients with metastatic ccRCC, irrespective of tumor PD-L1 expression. The role of earlier PD-1/PD-L1-directed therapy warrants evaluation in these patients.

scholarly journals Geospatial Cellular Distribution of Cancer-Associated Fibroblasts Significantly Impacts Clinical Outcomes in Metastatic Clear Cell Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3743
Author(s):  
Nicholas H. Chakiryan ◽  
Gregory J. Kimmel ◽  
Youngchul Kim ◽  
Joseph O. Johnson ◽  
Noel Clark ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Caspase 3 ◽  
Cox Regression ◽  
Clear Cell ◽  
Cancer Associated Fibroblasts ◽  
Tumor Cell Proliferation ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma ◽  
Ki 67

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point patterns were generated, which were then used to perform spatial analyses using a normalized Ripley’s K function at a radius of 25 μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups. Multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) <6 months, and therapy response was defined as PFS >9 months. CAFs exhibited higher cellular clustering with Ki-67+ cells than with caspase-3+ cells (nK(25): Ki-67 1.19; caspase-3 1.05; p = 0.04). The median nearest neighbor (NN) distance from CAFs to Ki-67+ cells was shorter compared to caspase-3+ cells (15 μm vs. 37 μm, respectively; p < 0.001). Multivariable Cox regression analyses demonstrated that both high Ki-67+ density and H-score were associated with worse OS, OS-IT, and OS-TT. Regarding αSMA+CAFs, only a high H-score was associated with worse OS, OS-IT, and OS-TT. For caspase-3+, high H-score and density were associated with worse OS and OS-TT. Patients whose tumors were resistant to targeted therapy (TT) had higher Ki-67 density and H-scores than those who had TT responses. Overall, this ex vivo geospatial analysis of CAF distribution suggests that close proximity clustering of tumor cells and CAFs potentiates tumor cell proliferation, resulting in worse OS and resistance to TT in metastatic ccRCC.

scholarly journals High Expression of CDCA7 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma and Its Associations With Immunity

2021 ◽  
Author(s):  
Shouyong Liu ◽  
Yi Wang ◽  
Chenkui Miao ◽  
Qianwei Xing ◽  
Zengjun Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Independent Prognostic Factor ◽  
Gene Set Enrichment Analysis ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract BackgroundCell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive role of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasis on immunity.MethodsThe RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated.ResultsOur results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P<0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P<0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. As for immunity, CDCA7 was significantly associated with tumor mutational burden (TMB), immune checkpoint molecules, tumor microenvironment and immune infiltration.ConclusionsCDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to immunity

scholarly journals Profiles of overall survival-related gene expression-based risk signature and their prognostic implications in clear cell renal cell carcinoma

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Zihao He ◽  
Tuo Deng ◽  
Xiaolu Duan ◽  
Guohua Zeng
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Family Member ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Training Set ◽  
Cell Renal Cell Carcinoma ◽  
Validation Set

Abstract The present work aimed to evaluate the prognostic value of overall survival (OS)-related genes in clear cell renal cell carcinoma (ccRCC) and to develop a nomogram for clinical use. Transcriptome data from The Cancer Genome Atlas (TCGA) were collected to screen differentially expressed genes (DEGs) between ccRCC patients with OS &gt; 5 years (149 patients) and those with &lt;1 year (52 patients). In TCGA training set (265 patients), seven DEGs (cytochrome P450 family 3 subfamily A member 7 (CYP3A7), contactin-associated protein family member 5 (CNTNAP5), adenylate cyclase 2 (ADCY2), TOX high mobility group box family member 3 (TOX3), plasminogen (PLG), enamelin (ENAM), and collagen type VII α 1 chain (COL7A1)) were further selected to build a prognostic risk signature by the least absolute shrinkage and selection operator (LASSO) Cox regression model. Survival analysis confirmed that the OS in the high-risk group was dramatically shorter than their low-risk counterparts. Next, univariate and multivariate Cox regression revealed the seven genes-based risk score, age, and Tumor, lymph Node, and Metastasis staging system (TNM) stage were independent prognostic factors to OS, based on which a novel nomogram was constructed and validated in both TCGA validation set (265 patients) and the International Cancer Genome Consortium cohort (ICGC, 84 patients). A decent predictive performance of the nomogram was observed, the C-indices and corresponding 95% confidence intervals of TCGA training set, validation set, and ICGC cohort were 0.78 (0.74–0.82), 0.75 (0.70–0.80), and 0.70 (0.60–0.80), respectively. Moreover, the calibration plots of 3- and 5 years survival probability indicated favorable curve-fitting performance in the above three groups. In conclusion, the proposed seven genes signature-based nomogram is a promising and robust tool for predicting the OS of ccRCC, which may help tailor individualized therapeutic strategies.

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