scholarly journals Analyzing and Validating the Prognostic Value of a TNF-Related Signature in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenhao Zhang ◽  
Changjiu Li ◽  
Fanding Wu ◽  
Ning Li ◽  
Yuwei Wang ◽  
...  

Background: Kidney renal clear cell carcinoma (KIRC) has the highest incidence rate in renal cell carcinoma (RCC). Although bioinformatics is widely used in cancer, few reliable biomarkers of KIRC have been found. Therefore, continued efforts are required to elucidate the potential mechanism of the biogenesis and progression of KIRC.Methods: We evaluated the expression of tumor necrosis factor (TNF) family genes in KIRC, and constructed a prognostic signature. We validated the signature by another database and explored the relationship between the signature and progression of KIRC. We assessed the prognostic value, immune infiltration, and tumor mutation burden (TMB) of the signature in KIRC.Results: We selected four key genes (TNFSF14, TNFRSF19, TNFRSF21, and EDA) to construct the TNF-related signature. We divided the KIRC patients into high- and low-risk groups based on the signature. Patients with higher risk scores had shorter overall survival and worse prognosis. With another database, we validated the value of the signature. The signature was considered as an independent risk factor. A higher level of risk score was relevant to higher level of immune infiltration, especially T regulatory cells, CD8+ T cells, and macrophages. The signature was also associated with TMB scores, and it may have an effect on assessing the efficacy of immunotherapy.Conclusion: This is the first TNF-family-related signature of KIRC and we demonstrated its effectiveness. It played a significant role in predicting the prognosis of patients with KIRC. It also has the potential to become a powerful tool in guiding the immunotherapy of KIRC patients in clinical practice.

2021 ◽  
Vol 20 ◽  
pp. 153303382110362
Author(s):  
Chujie Chen ◽  
Yiyu Sheng

Kidney renal clear cell carcinoma (KIRC) is one of the most malignant diseases with poor survival rate over the world. The tumor microenvironment (TME) is highly related to the oncogenesis, development, and prognosis of KIRC. Thus, making the identification of KIRC biomarkers and immune infiltrates critically important. Microtubule Interacting and Trafficking Domain containing 1(MITD1) was reported to participate in cytokinesis of cell division. In the present study, multiple bioinformatics tools and databases were applied to investigate the expression level and clinical value of MITD1 in KIRC. We found that the expression of MITD1 was significantly increased in KIRC tissues. Further, the KIRC patients with high MITD1 levels showed a worse overall survival (OS) rate and disease free survival (DFS) rate. Otherwise, we found a significant correlation MITD1 expression and the abundance of CD8+ T cells. Functional enrichment analyses revealed that immune response and cytokine-cytokine receptor are very critical signaling pathways which associated with MITD1 in KIRC. In conclusion, our findings indicated that MITD1 may be a potential biomarker and associated with immune infiltration in KIRC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zhuolun Sun ◽  
Changying Jing ◽  
Xudong Guo ◽  
Mingxiao Zhang ◽  
Feng Kong ◽  
...  

Kidney renal clear cell carcinoma (KIRC) has long been identified as a highly immune-infiltrated tumor. However, the underlying role of pyroptosis in the tumor microenvironment (TME) of KIRC remains poorly described. Herein, we systematically analyzed the prognostic value, role in the TME, response to ICIs, and drug sensitivity of pyroptosis-related genes (PRGs) in KIRC patients based on The Cancer Genome Atlas (TCGA) database. Cluster 2, by consensus clustering for 24 PRGs, presented a poor prognosis, likely because malignancy-related hallmarks were remarkably enriched. Additionally, we constructed a prognostic prediction model that discriminated well between high- and low-risk patients and was further confirmed in external E-MTAB-1980 cohort and HSP cohort. By further analyzing the TME based on the risk model, higher immune cell infiltration and lower tumor purity were found in the high-risk group, which presented a poor prognosis. Patients with high risk scores also exhibited higher ICI expression, indicating that these patients may be more prone to profit from ICIs. The sensitivity to anticancer drugs that correlated with model-related genes was also identified. Collectively, the pyroptosis-related prognosis risk model may improve prognostic information and provide directions for current research investigations on immunotherapeutic strategies for KIRC patients.


2004 ◽  
Vol 171 (6 Part 1) ◽  
pp. 2461-2466 ◽  
Author(s):  
MATTHEW H.T. BUI ◽  
HARRI VISAPAA ◽  
DAVID SELIGSON ◽  
HYUNG KIM ◽  
KEN-RYU HAN ◽  
...  

2021 ◽  
Author(s):  
Axiu Zheng ◽  
Jianrong Bai ◽  
Yanping Ha ◽  
Bingshu Wang ◽  
Yuan Zou ◽  
...  

Abstract Background Stonin 1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the role of STON1 in kidney renal clear cell carcinoma (KIRC). Methods We undertook bioinformatics analyses of a series of public databases to determine the expression and clinical significance of STON1 in KIRC and focused on STON1-related immunomodulator and survival signatures. A nomogram model integrating clinicopathological characteristics and risk scores for KIRC was established and validated. Results Through TGCA and GEO databases, STON1 mRNA was found to be significantly downregulated in KIRC compared with normal controls, and decreased STON1 was related to grade, TNM stage, distant metastasis, and vital status of KIRC. Furthermore, OncoLnc, UALCAN, Kaplan–Meier, and GEPIA2 analyses supported that KIRC patients with high STON1 expression had better overall survival. STON1 was positively associated with mismatch proteins including MLH1, PMS2, MSH2, MSH6 and EpCAM, and was negatively correlated with tumor mutational burden. Interestingly, arm-level deletion of STON1 was clearly related to the abundance of immune cells and the infiltration abundance in the majority of 26 immune cell types that were positively related to STON1 mRNA level in the TIMER database. The TISIDB database revealed 21 immunostimulators and 10 immunoinhibitors that were obviously related to STON1 in KIRC. In univariate and multivariate Cox regression analyses, CTLA4 , KDR , LAG3 , PDCD1 , HHLA2 , TNFRSF25 , and TNFSF14 were screened to establish a risk score model, and the low-risk group had a better prognosis for KIRC. Furthermore, a nomogram integrating clinicopathological characteristics and risk score had better accuracy and practicability in predicating the survival of KIRC patients. Conclusions Decreased STON1 expression in KIRC leads to clinical progression and poor survival. Mechanically, loss of STON1 is associated with the aberrant immune microenvironment in KIRC. Integrated clinicopathological characteristics and risk score derived from STON1 -related immunomodulators can aid the prediction of KIRC survival.


2020 ◽  
Vol 19 ◽  
pp. 153303382093668
Author(s):  
Haoyuan Cao ◽  
Jiandong Zhang ◽  
Wei Wang

Background: Disabled homolog 2-interacting protein is a new member of the Ras GTPase superfamily involved in the regulation of cell proliferation, apoptosis, and metastasis. However, the expression of disabled homolog 2-interacting protein in renal cell carcinoma, its correlation with cancer prognosis, and tumor infiltrating lymphocytes remains unclear. Methods: The expression of disabled homolog 2-interacting protein was analyzed by UALCAN database, GEPIA database and the evaluation of disabled homolog 2-interacting protein effects on clinical prognosis. Prognostic factor analysis was used to identify the correlations between disabled homolog 2-interacting protein and cancer immune infiltration via the TIMER database. In addition, COXPRESdb database was used to analyze the enrichment of disabled homolog 2-interacting protein co-expression genes. Results: Compared to the normal tissues, the messenger RNA expression levels of DAB2IP are higher in 8 while lower in 15 types of tumor tissues. Furthermore, disabled homolog 2-interacting protein has high expression in kidney chromophobe and low expression in both kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. The messenger RNA expression levels of disabled homolog 2-interacting protein decrease gradually due to the increasing tumor staging which positively correlates with disease-free survival and overall survival in both kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. The expression levels of disabled homolog 2-interacting protein also positively correlate with the tumor purity of kidney chromophobe, kidney renal clear cell carcinoma, and kidney renal papillary cell carcinoma samples. Besides, the expression of disabled homolog 2-interacting protein in renal cell carcinoma has negative correlation with the immune infiltration, and the immune infiltration of B cells and CD8+ T cells affects the prognosis of kidney renal papillary cell carcinoma. Enrichment analysis of disabled homolog 2-interacting protein co-expressed genes suggested that its biological role was mainly in regulating GTPase activity. Conclusions: These findings suggest that disabled homolog 2-interacting protein functions as a tumor suppressor in the progression of renal cell carcinoma, and the expression of disabled homolog 2-interacting protein is related to the immune infiltrating cells and affects the survival of renal cell carcinoma. Disabled homolog 2-interacting protein can be a novel clinical biomarker for patients with renal cell carcinoma, which also provides new insights for the future treatments of renal cell carcinoma.


2004 ◽  
Vol 171 (4S) ◽  
pp. 200-200 ◽  
Author(s):  
Matthew H. Bui ◽  
David B. Seligson ◽  
Hyung L. Kim ◽  
Ken Han ◽  
Yunda Huang ◽  
...  

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