scholarly journals Integrative Analysis of Immune-Related Genes in the Tumor Microenvironment of Renal Clear Cell Carcinoma and Renal Papillary Cell Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Zheng ◽  
Fang Xie ◽  
Fajuan Cheng ◽  
Jianwei Wang ◽  
Zhongshun Yao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Cell Cancer ◽  
Cancer Genome ◽  
Immune Related Genes

Kidney cancer encompasses a range of primary cancers, such as clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Our knowledge about the tumor microenvironment (TME) of kidney cancer is still limited. Therefore, we comprehensively assessed the TME of kidney cancers (including ccRCC and pRCC) using the ESTIAMTE, and CIBERSORT algorithms, and conducted distinct functional and correlation analyses with data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Connectivity map and CellMiner database. Next, we identified two immune-related hub genes, IGLL5 and IL2RA, which play essential roles in the TME as well as on survival in ccRCC and pRCC. Furthermore, ccRCC and pRCC samples from our medical center were collected to verify the clinical application value of these two immune-related genes. A specific enrichment analysis of immune cells related to IGLL5 and IL2RA was also conducted in two types of renal cell cancer. Based on selected genes, we predicted the drug response and uncovered novel drug candidate for RCC treatment. Considering the unfavorable outcomes of kidney cancer and emerging interest in TME-targeted treatments, our results may offer insights into immune-related molecular mechanisms and possible targets to control the kidney cancer.

scholarly journals Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary renal cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Meng ◽  
Luojin Zhang ◽  
Mingjun Zhang ◽  
Kaiqin Ye ◽  
Wei Guo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Functional Enrichment ◽  
Cancer Tissue ◽  
Down Regulation

Abstract Background BCL2L13 belongs to the BCL2 super family, with its protein product exhibits capacity of apoptosis-mediating in diversified cell lines. Previous studies have shown that BCL2L13 has functional consequence in several tumor types, including ALL and GBM, however, its function in kidney cancer remains as yet unclearly. Methods Multiple web-based portals were employed to analyze the effect of BCL2L13 in kidney cancer using the data from TCGA database. Functional enrichment analysis and hubs of BCL2L13 co-expressed genes in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were carried out on Cytoscape. Evaluation of BCL2L13 protein level was accomplished through immunohistochemistry on paraffin embedded renal cancer tissue sections. Western blotting and flow cytometry were implemented to further analyze the pro-apoptotic function of BCL2L13 in ccRCC cell line 786-0. Results BCL2L13 expression is significantly decreased in ccRCC and pRCC patients, however, mutations and copy number alterations are rarely observed. The poor prognosis of ccRCC that derived from down-regulated BCL2L13 is independent of patients’ gender or tumor grade. Furthermore, BCL2L13 only weakly correlates with the genes that mutated in kidney cancer or the genes that associated with inherited kidney cancer predisposing syndrome, while actively correlates with SLC25A4. As a downstream effector of BCL2L13 in its pro-apoptotic pathway, SLC25A4 is found as one of the hub genes that involved in the physiological function of BCL2L13 in kidney cancer tissues. Conclusions Down-regulation of BCL2L13 renders poor prognosis in ccRCC and pRCC. This disadvantageous factor is independent of any well-known kidney cancer related genes, so BCL2L13 can be used as an effective indicator for prognostic evaluation of renal cell carcinoma.

scholarly journals Metastatic renal cell carcinoma of unknown primary site. Clinical follow-up

2020 ◽  
Vol 22 (3) ◽  
pp. 149-153
Author(s):  
N. A. Ognerubov ◽  
T. S. Antipova ◽  
G. E. Gumareva
Keyword(s):  
Computed Tomography ◽  
Renal Cell Carcinoma ◽  
Adrenal Gland ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Primary Site ◽  
The Right

Renal cell cancer metastases without evidence of a primary tumor are extremely rare. These variants are usually showed as a spontaneous description of single clinical cases. Aim.This contribution is a clinical follow-up of synchronous renal cell cancer metastases of unknown primary site. Results.A 52-year-old patient U. with a history of increased blood pressure, up to 170/100 mmHg for the last 5 years, who had undergone many instrumental examinations, including ultrasound examination, because of this disease. The computed tomography of the abdomen showed a 4975 mm heterogeneous tumor in the right adrenal gland in October 2017. The combined positron emission and X-ray computed tomography showed a 795441 mm mass in the right adrenal gland, associated with elevated fluorodeoxyglucose metabolic activity SUVmax 7.25. Focal accumulation of the radiopharmaceutical SUVmax 4.31 in a 171124 mm mass was detected in the space of bifurcation in the mediastinum. The lytic lesion (1015 mm) was found in right superior L3 articular process. The patient underwent retroperitoneoscopic adrenalectomy and thoracoscopic removal of mediastinal tumor in November 2017 because of the oligometastatic nature of the process. The histological study identified clear-cell carcinoma with areas of papillary structure in the right adrenal gland. The immunohistochemical study showed carcinoma cells intensively expressing CD10, and some other cells RCC. The immune phenotype of the tumor was identified as clear-cell renal cell carcinoma. The immunohistological and immunohistochemical analysis reviled the metastases of the same variant of renal cell carcinoma in one of 9 lymph nodes. The patient was treated with pazopanib. The primary renal tumor was not detected during the dynamic observation, including the application of annual combined positron emission and X-ray computed tomography. The patient is alive without disease progression with a follow-up of 32 months. Conclusion.Metastases of clear-cell renal cell carcinoma, including adrenal gland, without evidence of a primary site are extremely rare. The main method of treatment is a combination of surgery and targeted therapy, providing long-term local control of the course of the disease.

scholarly journals Prognostic value of immune-related genes in clear cell renal cell carcinoma

Aging ◽  
2019 ◽  
Vol 11 (23) ◽  
pp. 11474-11489 ◽  
Author(s):  
Bangbei Wan ◽  
Bo Liu ◽  
Yuan Huang ◽  
Gang Yu ◽  
Cai Lv
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Immune Related Genes

scholarly journals Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8096 ◽  
Author(s):  
Haiping Zhang ◽  
Jian Zou ◽  
Ying Yin ◽  
Bo Zhang ◽  
Yaling Hu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Clinical Stage ◽  
Stage I ◽  
Differentially Expressed ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.

Malignant ascites as a manifestation of advanced papillary renal cell cancer (pRCC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 465-465 ◽  
Author(s):  
Julia C. Friend ◽  
Daniel Su ◽  
Rashmi Thimmapuram ◽  
James Peterson ◽  
Geri Hawks ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Clinical Characteristics ◽  
Clear Cell ◽  
Cell Cancer ◽  
Malignant Ascites ◽  
Urologic Oncology ◽  
True Incidence

465 Background: Peritoneal carcinomatosis and ascites are frequent and clinically challenging complications associated with several malignancies such as ovarian cancer. Although ascites is rarely reported in patients with advanced renal cell carcinoma (RCC), its true incidence, particularly in non-clear cell variants, remains poorly defined. Here, we describe the incidence of and clinical characteristics associated with ascites in patients with pRCC. Methods: Patients with metastatic renal cell carcinoma (RCC) seen at the NCI Urologic Oncology Branch were identified in a review of our clinical database. The incidence of radiologically and/or cytologically evident ascites, relevant associated clinical characteristics, and survival were evaluated as was the incidence of ascites in a contemporaneous clear cell RCC (ccRCC) cohort. Results: 241 patients with metastatic RCC were seen between 2002 and 2014, including 109 with pRCC and 125 with ccRCC. Seventeen patients with metastatic pRCC (17/109,15.5%) had evidence of malignant ascites, while only 1/125 pts (0.8%) with ccRCC developed this complication. Median age of PRCC patients with ascites was 45.8 years (range: 26.1 to 76.6 years). Ascites was seen in both patients with type 1 (15.6%, 10/64) and those with type 2 pRCC (15.5%, 7/45). Median time to development of ascites from initial diagnosis of metastatic disease was 16 months (95% CI 7-23 months). Median survival from diagnosis of metastatic disease was 25 months (95% CI 13-41months) in patients with ascites, compared to 20 (95% CI 14-31 months) in those without this complication. (p = 0.59). Conclusions: To our knowledge, this is the largest series evaluating the incidence of and outcome associated with ascites in RCC. Although rare in ccRCC, malignant ascites is a fairly common manifestation of metastatic pRCC. In our cohort, patients with ascites appeared to have outcomes comparable to patients with metastatic pRCC without ascites.

Single center validation of neutrophil-to-lymphocyte ratio in localized and metastatic clear cell renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 696-696
Author(s):  
Kevin Richard Melnick ◽  
Dattatraya H Patil ◽  
Amir Ishaq Khan ◽  
Frances Y Kim ◽  
Mersiha Torlak ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Renal Cell ◽  
Validation Cohort ◽  
Clear Cell ◽  
Independent Predictor ◽  
Prognostic Scores ◽  
Clinicopathologic Features

696 Background: The neutrophil-to-lymphocyte ratio (NLR) has been evaluated as a serum marker of inflammation and oncologic prognosis. In renal cell carcinoma (RCC), a higher preoperative NLR is associated with aggressive clinicopathologic features and is an independent predictor of poor survival. This study builds upon our institution’s prior work with the NLR in metastatic RCC and examines a larger validation cohort that includes localized disease. It also compares the predictive power of the NLR to established kidney cancer prognostic scores. Methods: Our kidney cancer database provided patients with clear cell RCC who underwent nephrectomy from January 2001 to June 2017 and had a documented preoperative NLR within 15 days prior to surgery. The optimal threshold of NLR was determined using receiver operating characteristic (ROC) curve and sensitivity-specificity trade-off analysis. Kaplan-Meier curves and logistic regression analysis were performed to assess the significance and independence of preoperative NLR in predicting OS. Finally, the prognostic ability of NLR was compared to current prognostic scores through chi-square analysis of their respective c-indices. Results: The 441 patient cohort was comprised of 361 patients with localized and/or regional disease and 80 patients with distant metastases. NLR values among all participants ranged from 0.4 to 74.0 (median 3.1). ROC analysis defined an optimal preoperative NLR threshold of 3.5. On multivariate analysis, after adjusting for clinicopathologic features and distant metastatic disease, a NLR ≥ 3.5 was found to be a significant and independent predictor of overall survival (HR = 1.41, 95% CI 1.05-1.91 & p value = 0.024). Our data also revealed no statistically significant difference between the c-indices of NLR and the UISS, SSIGN, or Leibovich scores in predicting survival. Conclusions: In our validation cohort of patients with both metastatic and non-metastatic clear cell RCC, our data show that a preoperative NLR ≥ 3.5 is a significant and independent predictor of overall survival in patients undergoing nephrectomy and is comparable to other established prognostic tools in RCC.

scholarly journals Targeting POLE2 Creates a Novel Vulnerability in Renal Cell Carcinoma via Modulating Stanniocalcin 1

2021 ◽  
Vol 9 ◽  
Author(s):  
Chuanjie Zhang ◽  
Yan Shen ◽  
Lili Gao ◽  
Xiaojing Wang ◽  
Da Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Cancer Genome ◽  
Clinicopathological Parameters ◽  
Expression Levels

ObjectiveThe aim of this study is to investigate the biological functions and the underlying mechanisms of DNA polymerase epsilon subunit 2 (POLE2) in renal cell carcinoma (RCC).MethodsThe datasets of POLE2 expression in The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) and International Cancer Genome Consortium (ICGC) databases was selected and the correlation between POLE2 and various clinicopathological parameters was analyzed. The POLE2 expression in RCC tissues was examined by immunohistochemistry. The POLE2 knockdown cell lines were constructed. In vitro and in vivo experiments were carried out to investigate the function of POLE2 on cellular biology of RCC, including cell viability assay, clone formation assay, flow cytometry, wound-healing assay, Transwell assay, qRT-PCR, Western blot, etc. Besides, microarray, co-immunoprecipitation, rescue experiment, and Western blot were used to investigate the molecular mechanisms underlying the functions of POLE2.ResultsPOLE2 was overexpressed in RCC tissues, and high expression of POLE2 was correlated with poor prognosis of RCC. Furthermore, knockdown of POLE2 significantly inhibited cell proliferation, migration, and facilitated apoptosis in vitro. In vivo experiments revealed that POLE2 attenuated RCC tumorigenesis and tumor growth. we also illuminated that stanniocalcin 1 (STC1) was a downstream gene of POLE2, which promoted the occurrence and development of RCC. Besides, knockdown of POLE2 significantly upregulated the expression levels of Bad and p21 while the expression levels of HSP70, IGF-I, IGF-II, survivin, and sTNF-R1 were significantly downregulated. Western blot analysis also showed that knockdown of POLE2 inhibited the expression levels of Cancer-related pathway proteins including p-Akt, CCND1, MAPK9, and PIK3CA.ConclusionKnockdown of POLE2 attenuates RCC cells proliferation and migration by regulating STC1, suggesting that POLE2-STC1 may become a potential target for RCC therapy.

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