Identification of the Prognostic Value Among Suppressor Of Cytokine Signaling Family Members in Kidney Renal Clear Cell Carcinoma

Background: Kidney renal clear cell carcinoma (KIRC) has become one of the most prevalent malignancies worldwide and remains a crucial cause of cancer-related morbidity and mortality. Aberrant activation of the JAK/STAT pathway acts as an important role in KIRC. The suppressor of cytokine signaling (SOCS) family members are the key negative regulators of the JAK/STAT pathway. SOCS family members have been verified to act as significant roles in regulating cellular responses to many cytokines and growth factors. However, whether the expression levels of SOCS affect the prognosis of patients with KIRC is still elusive.Methods: We first evaluated the expression of SOCS family genes in KIRC and determined the correlation between SOCS expression and different clinicopathological features. Then, we analyzed the genetic alterations, potential functions, transcription factor targets, and immune infiltration of SOCS family members based on the information available on public databases. Finally, we assessed the prognostic value of differentially expressed SOCS family members.Results: The expression levels of SOCS2, SOCS4, SOCS6, SOCS7, and CISH were downregulated in KIRC, and all SOCS genes were associated with clinicopathological features of patients with KIRC. SOCS family members have been predominantly related to protein binding, signaling adaptor activity, and JAK/STAT cascade. We found that STAT3, STAT6, and IRF1 are the key transcription factors that may be participated in the regulation of SOCS. We also found an association between the expression levels of SOCS and the immune infiltrates of KIRC. Finally, we have illuminated that SOCS1 and SOCS3 are risky genes, whereas SOCS2, SOCS4, SOCS6, SOCS7, and CISH are some of the protective genes for patients with KIRC; based on these, we have created a KIRC prognostic index for predicting the prognosis of patients of KIRC.Conclusion: Our study may contribute to further understanding the functions of SOCS genes in KIRC, which may help clinicians in selecting the appropriate drugs and predicting the outcomes for patients with KIRC.

Download Full-text

Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

Cancer Medicine ◽

10.1002/cam4.3472 ◽

2020 ◽

Vol 9 (22) ◽

pp. 8624-8638 ◽

Cited By ~ 1

Author(s):

Shitong Lin ◽

Lingling Zheng ◽

Yuchao Lu ◽

Qidong Xia ◽

Peng Zhou ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Comprehensive Analysis ◽

Expression Levels

Download Full-text

Comprehensive Analysis of ATP6V1s Family Members in Renal Clear Cell Carcinoma With Prognostic Values

Frontiers in Oncology ◽

10.3389/fonc.2020.567970 ◽

2020 ◽

Vol 10 ◽

Author(s):

Xiaojuan Li ◽

Hao Li ◽

Caihong Yang ◽

Liu Liu ◽

Sisi Deng ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Family Members ◽

Renal Clear Cell Carcinoma ◽

Comprehensive Analysis

Download Full-text

PROGNOSTIC VALUE OF CARBONIC ANHYDRASE IX AND KI67 AS PREDICTORS OF SURVIVAL FOR RENAL CLEAR CELL CARCINOMA

The Journal of Urology ◽

10.1097/01.ju.0000116444.08690.e2 ◽

2004 ◽

Vol 171 (6 Part 1) ◽

pp. 2461-2466 ◽

Cited By ~ 116

Author(s):

MATTHEW H.T. BUI ◽

HARRI VISAPAA ◽

DAVID SELIGSON ◽

HYUNG KIM ◽

KEN-RYU HAN ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Cell Carcinoma ◽

Prognostic Value ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Carbonic Anhydrase Ix

Download Full-text

Identification of the Prognosis Value and Potential Mechanism of Immune Checkpoints in Renal Clear Cell Carcinoma Microenvironment

Frontiers in Oncology ◽

10.3389/fonc.2021.720125 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guodong Liao ◽

Ping Wang ◽

Yuyong Wang

Keyword(s):

Immune Checkpoint ◽

Prognostic Value ◽

Immune Cell ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Immune Checkpoints ◽

Immune Cell Infiltration ◽

Free Survival ◽

Checkpoint Genes

BackgroundKidney Renal Clear Cell Carcinoma (KIRC) is one of the most prevalent types of cancer worldwide. KIRC has a poor prognosis and, to date, immunotherapy based on immune checkpoints is the most promising treatment. However, the role of immune checkpoints in KIRC remains ambiguous.MethodsBioinformatics analyses and qRT-PCR were performed to explore and further confirm the prognostic value of immune checkpoint genes and their correlation with immune infiltration in KIRC samples.ResultsThe expression of the immune checkpoint genes CD274, PDCD1LG2, HAVCR2, CTLA4, TIGFT, LAG3, and PDCD1 was upregulated in KIRC tissues. These genes were involved in the activation of the apoptosis pathway in KIRC. Low expression of CD274 and HAVCR2 and high expression of CTLA4 were associated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of KIRC patients. The univariate and multivariate analyses revealed that CTLA4, HAVCR2, age, pTNM stage, and tumor grade were independent factors affecting the prognosis of KIRC patients. A predictive nomogram demonstrated that the calibration plots for the 3‐year and 5‐year OS probabilities showed good agreement compared to the actual OS of KIRC patients. The expression of CTLA4 and HAVCR2 were positively associated with immune cell infiltration, immune biomarkers, chemokines, and chemokine receptors. Moreover, miR-20b-5p was identified as a potential miRNA target of CTLA4 in KIRC.ConclusionOur study clarified the prognostic value of several immune checkpoint regulators in KIRC, revealing a CTLA4/miR-20b-5p axis in the control of immune cell infiltration in the tumor microenvironment.

Download Full-text

The prognostic value and immunological role of the small mother against decapentaplegic proteins in kidney renal clear cell carcinoma

Translational Cancer Research ◽

10.21037/tcr-21-178 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Siyue Zhang ◽

Zhuang Liu ◽

Mingming Xiao ◽

Hong Liu

Keyword(s):

Cell Carcinoma ◽

Prognostic Value ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma

Download Full-text

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

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.689037 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wenhao Zhang ◽

Changjiu Li ◽

Fanding Wu ◽

Ning Li ◽

Yuwei Wang ◽

...

Keyword(s):

Cell Carcinoma ◽

Prognostic Value ◽

T Regulatory Cells ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Risk Groups ◽

Renal Clear Cell Carcinoma ◽

Risk Scores ◽

Immune Infiltration ◽

Mutation Burden

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.

Download Full-text

DAB2IP Plays Important Clinical Significance and Correlates With Immune Infiltration in Renal Cell Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820936682 ◽

2020 ◽

Vol 19 ◽

pp. 153303382093668

Author(s):

Haoyuan Cao ◽

Jiandong Zhang ◽

Wei Wang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Messenger Rna ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Interacting Protein ◽

Expression Levels ◽

Immune Infiltration

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.

Download Full-text