scholarly journals Abnormal Expression and Prognosis Value of COG Complex Members in Kidney Renal Clear Cell Carcinoma (KIRC)

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Yanjun Zhang ◽  
Hui Lai ◽  
Bin Tang

Kidney renal clear cell carcinoma (KIRC) is the most aggressive subtype of kidney tumours with poor prognosis as well as the increasing incidence rate in worldwide. The conserved oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein that controls membrane trafficking and protein glycosylation and plays vital roles in human disease including cancers. Therefore, to uncover the prognostic value of COG complex in KIRC, a series of databases, including UALCAN database, GEPIA database, and Kaplan-Meier plotter, were used to analyse the mRNA expression of COG complex subunits and their prognostic values in patients with KIRC in this study. Compared with normal counterparts, mRNA expression of six COG complex subunits was significantly downregulated in KIRC tissue in UALCAN database, while COG4 mRNA expression was significantly upregulated in KIRC tissue. Moreover, the survival analysis indicated that all members of COG complex subunits were closely related with the prognosis of KIRC patients, while COG1 and COG4 were significantly associated with unfavourable overall survival (OS), the rest of COG complex subunits were importantly correlated with favourable OS. Simultaneously, higher mRNA expression of COG3, COG6, and COG8 exhibits better progression-free survival (PFS) and disease-free survival (DFS) in KIRC patients. These results identified that COG complex subunits, especially COG3, COG6, and COG8, are potential prognostic biomarkers of KIRC patients and may offer effective and new strategies for more accurately diagnosing the patients with KIRC in advance.

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 ◽  
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 18 (6) ◽  
pp. 8559-8576
Author(s):  
Xiuxian Zhu ◽  
◽  
Xianxiong Ma ◽  
Chuanqing Wu

<abstract> <sec><title>Background</title><p>Various studies have suggested that the DNA methylation signatures were promising to identify novel hallmarks for predicting prognosis of cancer. However, few studies have explored the capacity of DNA methylation for prognostic prediction in patients with kidney renal clear cell carcinoma (KIRC). It's very promising to develop a methylomics-related signature for predicting prognosis of KIRC.</p> </sec> <sec><title>Methods</title><p>The 282 patients with complete DNA methylation data and corresponding clinical information were selected to construct the prognostic model. The 282 patients were grouped into a training set (70%, n = 198 samples) to determine a prognostic predictor by univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. The internal validation set (30%, n = 84) and an external validation set (E-MTAB-3274) were used to validate the predictive value of the predictor by receiver operating characteristic (ROC) analysis and Kaplan–Meier survival analysis.</p> </sec> <sec><title>Results</title><p>We successfully identified a 9-DNA methylation signature for recurrence free survival (RFS) of KIRC patients. We proved the strong robustness of the 9-DNA methylation signature for predicting RFS through ROC analysis (AUC at 1, 3, 5 years in internal dataset (0.859, 0.840, 0.817, respectively), external validation dataset (0.674, 0.739, 0.793, respectively), entire TCGA dataset (0.834, 0.862, 0.842, respectively)). In addition, a nomogram combining methylation risk score with the conventional clinic-related covariates was constructed to improve the prognostic predicted ability for KIRC patients. The result implied a good performance of the nomogram.</p> </sec> <sec><title>Conclusions</title><p>we successfully identified a DNA methylation-associated nomogram, which was helpful in improving the prognostic predictive ability of KIRC patients.</p> </sec> </abstract>


2013 ◽  
Vol 66 (7) ◽  
pp. 613-619 ◽  
Author(s):  
Naoki Kanomata ◽  
Yasufumi Sato ◽  
Yoshiyuki Miyaji ◽  
Atsushi Nagai ◽  
Takuya Moriya

BackgroundVasohibin-1 (VASH1) is an endothelium-produced angiogenesis inhibitor. Renal cell carcinoma is highly vascularised, but the significance of endogenous VASH1 in renal cell carcinoma has not been defined.AimsTo identify VASH1 expression and its possible relationship with various clinicopathological factors and prognosis in renal cell carcinoma.MethodsA retrospective analysis of 122 tumours obtained from 118 consecutive patients with renal cell carcinoma was performed. The expression patterns of VASH1, CD31, vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2) were examined immunohistochemically and their relationships with clinicopathological factors were analysed.ResultsMicrovessel density, VASH1 and VEGFR2 expression were significantly higher in clear cell carcinoma than in other subtypes. The VEGF expression pattern differed significantly between clear cell carcinoma and other histological subtypes. VASH1, pT factor and TNM stage were significantly associated with disease-free survival (p=0.030, p = 0.0012 and p = 0.0018, respectively). Cox models of multivariable disease-free survival analyses indicated that VASH1 and stage are independent prognostic factors (p=0.019 and p = 0.024).ConclusionsVASH1 expression may be useful for estimating the prognosis of renal cell carcinoma. Further studies of the role of VASH1 in renal cell carcinoma involving larger sample sizes are warranted.


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.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Qian Wang ◽  
Hao Zhang ◽  
Quanbing Chen ◽  
Zhenghua Wan ◽  
Xiaoyong Gao ◽  
...  

The kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of the renal cell carcinoma, accounting for 80–90% of patients. Currently, the N6-methyladenosine (m6A) epitranscriptional modification draws much attention. The m6A RNA modification, the most plentiful internal modification of mRNAs and noncoding RNAs in the majority of eukaryotes, regulates mRNAs at different levels and is involved in disease occurrence and progression. The GTExPortal and TCGAportal were applied to investigate the METTL14 mRNA expression in different tissues and KIRC stages. The Human Protein Atlas was used to verify the location of METTL14 in KIRC tissues. The main microRNAs (miRNAs) related to KIRC were analyzed using OncoLnc and starBase, while corresponding circular RNAs (circRNAs) interacting with miRNAs were predicted via circBank; then, the METTL14-miRNA-circRNA interaction network was established. The level of methyltransferase-like 14 (METTL14) mRNA was significantly lower in KIRC tissues compared with normal kidney tissues, which was relative to clinical and pathological stages. circRNAs may regulate METTL14 mRNA as miRNAs sponge to affect the KIRC progression. METTL14 mRNA is likely to regulate PTEN mRNA expression via changing its m6A RNA modification level. METTL14 mRNA expression negatively correlated with the KIRC stages and positively correlated with KIRC patients’ overall survival, which has great potential to serve as a clinical biomarker in KIRC.


Author(s):  
Yan Liu ◽  
Changzhen Huang ◽  
Ran Chu ◽  
Xingsheng Yang ◽  
Beihua Kong ◽  
...  

Background: The treatment strategies for ovarian clear cell carcinoma (OCCC) are the same as those for epithelial ovarian cancer. Due to the rarity of OCCC, no prospective studies of its surgery have been reported. Therefore, the therapeutic significance of lymphadenectomy for OCCC needs to be further clarified. Objectives: To assess the effectiveness of lymphadenectomy in patients with ovarian clear cell carcinoma by a meta-analysis. Search Strategy: The Web of Science, Scopus, PubMed, and other sources (e.g. Google Scholar) were searched from each database’s earliest inception to June 2021. Selection Criteria: English-language publications of observational studies that investigated the role of lymphadenectomy in patients with OCCC were included. Data Collection and Analysis: The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated. Main Results: The analysis demonstrated that lymphadenectomy is associated with significantly improved disease-specific survival (DSS) (HR=0.76; 95%CI=0.60-0.95; P=0.02; I2= 0.0%) and disease-free survival (DFS) (HR=0.58; 95%CI=0.33-1.00; P=0.05; I2=61%), but not for overall survival (OS) (HR=0.80; 95%CI=0.60-1.06; P=0.12; I2= 19%) and progression-free survival (PFS) (HR=0.95; 95%CI=0.64-1.42; P=0.79; I2= 0.0%). But it is worth noting that several single studies indicated a tendency of improved OS, PFS, DFS, DSS with lymphadenectomy. Conclusions: Lymphadenectomy could not significantly improve OS and PFS for OCCC, but is associated with improved DFS and DSS. Gynecologic oncologists should tailor treatment to patients to achieve optimal outcomes. And further studies are necessary to validate the impact of lymphadenectomy on OCCC. Keywords: ovarian clear cell carcinoma, lymphadenectomy, survival, systematic review, meta- analysis


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xinwei Ma ◽  
Xiaoqi Wang ◽  
Qian Dong ◽  
Hongquan Pang ◽  
Jianming Xu ◽  
...  

Abstract Background Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, whose incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, although there is yet no report on its expression in ccRCC. Methods The expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP databases. In addition, GEPIA database predicted the relationship between IRF6 and KIF20A expressions and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP assays. The specific effects of IRF6 on ccRCC cell proliferation, invasion and apoptosis were subsequently examined at both cellular level and animal level. Results The database predicted down-regulated IRF6 expression in renal carcinoma tissues and its correlation with poor prognosis. IRF6 overexpression inhibited cRCC cell proliferation, invasion and migration. In addition, up-regulated KIF20A expression in renal carcinoma tissues and its association with prognosis were also predicted. Interference with KIF20A inhibited the proliferation, invasion, and migration of ccRCC cells. Finally, we confirmed that KIF20A is a functional target of IRF6 and can partially reverse the effects of IRF6 on the proliferation, invasion and migration of ccRCC cells. Conclusion: Inhibition of KIF20A by transcription factor IRF6 affects cell proliferation, invasion and migration in renal clear cell carcinoma.


2013 ◽  
Vol 13 (2) ◽  
pp. 79-80
Author(s):  
Zane Simtniece ◽  
Gatis Kirsakmens ◽  
Ilze Strumfa ◽  
Andrejs Vanags ◽  
Maris Pavars ◽  
...  

Abstract Here, we report surgical treatment of a patient presenting with pancreatic metastasis (MTS) of renal clear cell carcinoma (RCC) 11 years after nephrectomy. RCC is one of few cancers that metastasise in pancreas. Jaundice, abdominal pain or gastrointestinal bleeding can develop; however, asymptomatic MTS can be discovered by follow-up after removal of the primary tumour. The patient, 67-year-old female was radiologically diagnosed with a clinically silent mass in the pancreatic body and underwent distal pancreatic resection. The postoperative period was smooth. Four months after the surgery, there were no signs of disease progression.


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