scholarly journals Prognostic Impact of MITD1 and Associates With Immune Infiltration in Kidney Renal Clear Cell Carcinoma

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 2021 ◽  
pp. 1-18
Author(s):  
Ya Li ◽  
Chong Wang ◽  
Yang Gao ◽  
Liang Zhou

Background. Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy. The therapeutic strategies for advanced KIRC are very few, with only sunitinib being widely approved. Mutations in the PIK3CA gene can affect tumor cell proliferation, metastasis, and patients’ survival. Methods. Bioinformatics analysis was performed to explore the expression and clinical significance of PIK3CA in KIRC. Moreover, qRT-PCR was conducted to verify the result. Results. Subgroup analyses of KIRC tissue based on gender, tumor grade, and cancer stage indicated downregulation of PIK3CA mRNA expression. The KIRC patients with high PIK3CA expression indicated a better overall survival, progression-free survival, and disease-free survival. A predictive nomogram was constructed and demonstrated that the calibration plots for the 3-year and 5-year OS rates were predicted relatively well compared with an ideal model in the TCGA KIRC cohort. The validation study revealed that downregulation of PIK3CA in KIRC tissues and low PIK3CA expression had a poor overall survival with an AUC of 0.775 in the ROC curve. Moreover, Cox regression analysis revealed that PIK3CA expression and clinical stage were independent factors affecting the prognosis of KIRC patients. PIK3CA expression was found to be significantly associated with the abundance of immune cells and immune biomarker sets. PIK3CA and associated genes were found to be mainly associated with immune response and the JAK-STAT signaling pathway. Conclusion. We identified PIK3CA as a potential biomarker for prognosis correlated with immune infiltrates in KIRC. Further studies should focus on the functions of PIK3CA in KIRC carcinogenesis.


2021 ◽  
Author(s):  
Rongjiong Zheng ◽  
Yaosen SHao ◽  
Mingming Wang ◽  
Yeli Tang ◽  
Meiling Hu

Abstract BackgroundTumor microenvironment has been implicated in the development and progression of cancers. However, the prognostic significance of tumor microenvironment-related genes in kidney renal clear cell carcinoma (KIRC) remains unclear. MethodsIn this study, we obtained and analyzed gene expression profiles from The Cancer Genome Atlas database. Stromal and immune scores were calculated based on the ESTIMATE algorithm. ResultsIn the discovery series of 537 patients, we identified a list of differentially expressed genes which was significantly associated with prognosis in KIRC patients. Protein-protein interaction networks and functional enrichment analysis were both performed, indicating that these identified genes were related to the immune response. ConclusionsThe tumor microenvironment-related genes could serve as the potential biomarkers for KIRC.


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.


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.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lishan He ◽  
Huiming Jiang ◽  
Zhenqiang Lai ◽  
Zhixiong Zhong ◽  
Zhanqin Huang

Abstract Background Syntaxin4 (STX4) gene encodes the protein STX4, a member of soluble N-ethylmaleimide-sensitive factor attachment protein receptors protein, playing a vital role in cell invadopodium formation and invasion, which is associated with the malignant progression of various human cancers. However, the expression and prognostic significance of STX4 in kidney renal clear cell carcinoma (KIRC) remain to be investigated. Methods In this study, we collected the mRNA expression of STX4 in 535 KIRC patients from The Cancer Genome Atlasthrough the University of California Santa Cruz Xena database platform. Then we explored the expression of STX4 in KIRC, and the relationship with clinicopathological characteristics and prognostic value. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes function enrichment analyses were used to explore the potential mechanism of STX4 in KIRC. qRT-PCR analysis was performed toverify the above results with real world tissue specimens. Results The results indicated that STX4 was up-expressed in KIRC, and were associated with higher histological grade, advanced stage, and poorer prognosis. Moreover, elevated STX4 expression is an independent risk factor for KIRC. qRT-PCR analysis showed that STX4 was significantly elevated in 10 paired of KIRC samples compared to normal samples. Functional enrichment analysis indicated that endo/exocytosis, autophagy, mTOR signaling pathway, and NOD-like receptor signaling pathway were enriched. Conclusions In summary, STX4 is constantly up-expressed in KIRC tissues, associated with a poor prognosis. We suggest that it can be an effective biomarker for the prognosis of KIRC and may be a novel therapeutic target in KIRC.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yonghui Gui ◽  
Xueni Liu ◽  
Chao Wang ◽  
Peng Yang

Abstract Background Pituitary tumor transforming genes (PTTG1, PTTG2, and PTTG3P) play key roles in the pathogenesis and development of human cancers. The studies show that overexpression of the PTTG genes is associated with tumor progression and migration. However, the function of the PTTG genes in the prognostic value of kidney renal clear cell carcinoma is rarely known by people. Methods The expression of PTTG family genes was analyzed by the ONCOMINE, Human Protein Atlas, GEPIA2, and UALCAN database. The relationship between PTTG family genes expression level and clinical indicators including prognostic data in kidney renal clear cell carcinoma was analyzed by GEPIA2, TCGA portal, and UALCAN. cBioPortal database was used to analyze the genetic mutations of differentially expressed PTTG family members. Similar genes of the PTTG family (90 in total) obtained from GEPIA2 and Metascape were used for GO enrichment to explore the interaction among similar genes. The online tools of Metascape and STRING were used for functional and pathway enrichment analysis. Results PTTG1, 2, and 3P mRNA and protein expression upregulated in kidney renal clear cell carcinoma kidney renal clear cell carcinoma patients compared with normal tissues. And higher expression level of PTTG family genes was associated with shorter overall survival (OS) and disease-free survival (DFS). Furthermore, overexpression of the PTTG family genes had been found correlated with individual cancer stages and pathological tumor grades. In addition, 18% of mutations in the PTTG family genes were associated with short-term survival in kidney renal clear cell carcinoma patients. Conclusions A single PTTG gene or PTTG family genes as a whole may be a potential prognostic biomarker for kidney renal clear cell carcinoma.


2021 ◽  
Vol 11 (4) ◽  
pp. 263
Author(s):  
Hyo Jae Shin ◽  
Kyung Jin Lee ◽  
Minchan Gil

Cereblon (CRBN) is a component of the E3 ubiquitin ligase complex that plays crucial roles in various cellular processes. However, no systematic studies on the expression and functions of CRBN in solid tumors have been conducted to date. Here, we analyzed CRBN expression and its clinical value using several bioinformatic databases. CRBN mRNA expression was downregulated in various cancer types compared to normal cells. Survival analysis demonstrated that overall survival was significantly positively correlated with CRBN expression in some cancer types including lung adenocarcinoma (LUAD), kidney renal clear cell carcinoma (KIRC), and skin cutaneous melanoma (SKCM). CRBN expression was downregulated regardless of clinicopathological characteristics in LUAD and KIRC. Analysis of genes that are commonly correlated with CRBN expression among KIRC, LUAD, and SKCM samples elucidated the potential CRBN-associated mechanisms of cancer progression. Overall, this study revealed the prognostic value of CRBN and its potential associated mechanisms, which may facilitate the development of anti-cancer therapeutic agents.


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