scholarly journals Variation in gene encoding the co-inhibitory molecule BTLA is associated with survival in patients treated for clear cell renal carcinoma – results of a prospective cohort study

2021 ◽  
Author(s):  
Krzysztof Tupikowski ◽  
Anna Partyka ◽  
Edyta Pawlak ◽  
Kuba Ptaszkowski ◽  
Romuald Zdrojowy ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
T Cell Response ◽  
Disease Stage ◽  
Tumor Diameter ◽  
Gene Encoding ◽  
Cell Renal Cell Carcinoma

IntroductionThe successful introduction of immune checkpoint blockade approaches to renal-cell carcinoma (RCC) treatment indicates the importance of molecules regulating the T cell response to RCC risk and progression.Material and methodsIn this study, we evaluate the association of variations in the CTLA-4, BTLA and CD28 genes with overall survival (OS) of RCC patients and specifically clear cell RCC (ccRCC) patients. The following previously genotyped using RFLP method or TaqManSNP Genotyping Assays single nucleotide polymorphisms (SNPs) were analyzed: CTLA-4 gene: c.49A>G (rs231775), g.319C>T (rs5742909), g.*6230G>A (CT60; rs3087243), g.*10223G>T (Jo31; rs11571302); CD28 gene: c.17+3T>C (rs3116496), c.-1042G>A (rs3181098); BTLA gene: rs2705511, rs1982809, rs9288952, rs9288953, rs2705535 and rs1844089.ResultsDuring long term observation (6.5 years) we discovered that possessing of A allele at BTLA rs1844089 SNP, together with advanced disease (stage >3, tumor grade >3, tumor diameter ≥70mm), is an independent risk factor of death which increases the HR (hazard ratio) of death by more than two-fold (HR=2.21, 95%CI 1.28-3.83). Furthermore, the OS of patients bearing this allele is 6 months shorter than for homozygous [GG] patients (42.5 vs. 48.2 months).ConclusionsOur results indicate for the first time that genetic variation within the gene encoding the BTLA is significantly associated with overall survival in clear cell renal cell carcinoma patients.

Tumor diameter response in patients with metastatic clear cell renal cell carcinoma is associated with overall survival

2021 ◽  
Author(s):  
Alberto C. Pieretti ◽  
Daniel D. Shapiro ◽  
Mary E. Westerman ◽  
Hyunsoo Hwang ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Diameter ◽  
Cell Renal Cell Carcinoma

scholarly journals Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jazmine Arévalo ◽  
David Lorente ◽  
Enrique Trilla ◽  
María Teresa Salcedo ◽  
Juan Morote ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Independent Manner ◽  
Fuhrman Grade ◽  
Transcription 3 ◽  
Aggressive Subtype

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.

scholarly journals A united risk model of 11 immune‑related gene pairs and clinical stage for prediction of overall survival in clear cell renal cell carcinoma patients

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 4259-4277
Author(s):  
Zijia Tao ◽  
Enchong Zhang ◽  
Lei Li ◽  
Jianyi Zheng ◽  
Yiqiao Zhao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Risk Model ◽  
Clear Cell ◽  
Clinical Stage ◽  
Related Gene ◽  
Cell Renal Cell Carcinoma ◽  
Immune Related Gene

76P B7-H3 immune checkpoint protein expression is associated with immune exhaustion, overall survival and metastasis in clear cell renal cell carcinoma

2021 ◽  
Vol 32 ◽  
pp. S1368
Author(s):  
C.E. Nunes-Xavier ◽  
M. Emaldi ◽  
T. Øyjord ◽  
G. Larrinaga ◽  
P. Errarte ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Checkpoint Protein ◽  
Immune Exhaustion

Factors Influencing Overall Survival for Patients With Metastatic Clear-Cell Renal-Cell Carcinoma in Daily Practice

2018 ◽  
Vol 16 (2) ◽  
pp. e297-e305 ◽  
Author(s):  
Antoine Thiery-Vuillemin ◽  
Tiphaine Cholley ◽  
Fabien Calcagno ◽  
Marion Hugues ◽  
Tristan Maurina ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Daily Practice ◽  
Cell Renal Cell Carcinoma ◽  
Factors Influencing

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.

scholarly journals PD49-09 SPATIAL CLUSTERING OF CD68+ TUMOR ASSOCIATED MACROPHAGES WITH TUMOR CELLS IS ASSOCIATED WITH WORSE OVERALL SURVIVAL IN METASTATIC CLEAR CELL RENAL CELL CARCINOMA

2021 ◽  
Vol 206 (Supplement 3) ◽  
Author(s):  
Nicholas Chakiryan ◽  
Ali Hajiran ◽  
Youngchul Kim ◽  
Jad Chahoud ◽  
Philippe Spiess ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Spatial Clustering ◽  
Tumor Associated Macrophages ◽  
Cell Renal Cell Carcinoma

Tumor-infiltrating regulatory T lymphocytes orchestrate oncogenic PAK1-conferred immune evasion in clear-cell renal cell carcinoma

2019 ◽  
Author(s):  
Yang Qu ◽  
Jiajun Wang ◽  
Qi Bai ◽  
Yangyang Qi ◽  
Yifan Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
T Lymphocytes ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Regulatory T Lymphocytes ◽  
Tumor Tissues ◽  
Pak1 Expression

Abstract Background: Little is known about the associations between PAK1 and anti-tumor immunity in clear-cell renal cell carcinoma (ccRCC). This study aims to explore the prognostic value of PAK1 in ccRCC patients and investigated the molecular immune mechanism for its oncogenic role. Methods: We retrospectively enrolled 282 ccRCC patients undergoing nephrectomy between 2005 and 2007 in Zhongshan hospital. Immunohistochemistry evaluated PAK1, CCL22, FOXP3 and CD8 expression in clinical specimens. Fresh tumor tissues, para-tumor tissues and peripheral blood samples for RT-PCR, ELISA, flow cytometry analyses were collected from patients who underwent nephrectomy in Zhongshan Hospital from September 2017 to April 2018. We compared clinical outcomes by Kaplan-Meier survival analysis and Cox regression model. Bioinformatics analysis performed in TCGA KIRC cohort. Results: High PAK1 expression indicated poorer overall survival (OS) and recurrence free survival (RFS) (both p<0.001) in ccRCC patients. Multivariate analyses indicated PAK1 as an independent prognostic factor. In clinical samples, PAK1 clearly correlated with immunosuppressive microenvironment in ccRCC tissues. Significantly, PAK1 positively correlated with Tumor-infiltrating regulatory T lymphocytes (Tregs). Furthermore, IL-10+ and TGF-β+ tumor-infiltrating Tregs both increased in PAK1 high tumors. Additionally, CCL22 was highly secreted in PAK1 high tumors. After treated by IPA-3 (an PAK1 inhibitor), CCL22 secretion was clearly inhibited (p<0.001). Finally, we built a nomogram to predict overall survival for ccRCC patients with higher predictive accuracy. Conclusions: Increased PAK1 expression predicted dismal prognosis in ccRCC patients by inducing tumor immune escape. IL-10+ and TGF-β+ tumor-infiltrating Tregs recruited by CCL22 play dominant immunosuppressive roles in PAK1 high tumors.

scholarly journals Nomograms for predicting long-term overall survival and disease-specific survival of patients with clear cell renal cell carcinoma

2018 ◽  
Vol Volume 11 ◽  
pp. 5535-5544 ◽  
Author(s):  
Guanghao Zhang ◽  
Yun Wu ◽  
Jiashu Zhang ◽  
Zhiqing Fang ◽  
Zhaoxu Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Disease Specific Survival ◽  
Cell Renal Cell Carcinoma ◽  
Disease Specific

scholarly journals Identification of a Novel Signature and Construction of a Nomogram Predicting Overall Survival in Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiangkun Wu ◽  
Zhijian Zhao ◽  
Aisha Khan ◽  
Chao Cai ◽  
Daojun Lv ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma
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