scholarly journals Overexpression of Spondin-2 Is Associated with Recurrence-Free Survival in Patients with Localized Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Hui-Min Ma ◽  
Meng Yu ◽  
Cong Wu ◽  
Hou-Bao Huang ◽  
Ya-Wei Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Recurrence Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Invasion And Migration ◽  
And Migration

Background. The spondin-2 (SPON2) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in clear cell renal cell carcinoma (ccRCC) are still unclear. Methods. SPON2 expression in ccRCC was evaluated using expression data from TCGA and GEO databases, then confirmed by local patient population (94 patients). The clinical significance of SPON2 expression was evaluated. Downregulation of SPON2 was performed using small-interfering RNA (siRNA). The effects of SPON2 silencing on cell proliferation, apoptosis, invasion, and migration in vitro were investigated. Results. SPON2 was overexpressed in the majority of the ccRCC at both mRNA and protein levels. SPON2 expression was significantly correlated with stage, grade, and recurrence (all P<0.05) in patients with localized ccRCC. The receiver operating characteristic (ROC) curve showed that SPON2 expression could serve as a predictor of recurrence. SPON2 expression was significantly associated with recurrence-free survival (RFS) in patients with localized ccRCC. Knocking down SPON2 resulted in suppressed cell invasion and migration in vitro. Conclusion. SPON2 expression might function as a prognostic biomarker in patients with localized ccRCC.

A validated 34-gene signature for assessing risk of recurrence in clear cell renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4522-4522
Author(s):  
Kimryn Rathmell ◽  
Samira A Brooks ◽  
Angela Rose Brannon ◽  
Joel S Parker ◽  
Jennifer C Fisher ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Biology ◽  
Clear Cell ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Recurrence Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

4522 Background: The objective of this study is to create a molecular tool that can be applied widely to clinical specimens using existing transcript signatures for use in clinical risk prediction of clear cell Renal Cell Carcinoma (ccRCC) to improve personalized disease management. Methods: We developed a 34-gene subtype predictor to classify clear cell tumors according to two subtypes, clear cell A (ccA) or B (ccB). The training set consisted of 72 ccRCC microarray-analyzed tumor samples that had previously been classified by unsupervised clustering and logical analysis of data (LAD). The predictor was developed from a panel of genes significantly expressed in ccA and ccB tumors and associated with prognosis. The prognostic value of the algorithm was corroborated in RNA-sequencing data from 379 ccRCC samples from The Cancer Genome Atlas (TCGA) and further validated using the NanoString platform with a cohort of 163 archival fixed samples collected at the University of North Carolina. Results: Risk associated molecular subtypes, ccA and ccB, were classified in TCGA and NanoString cohorts. Subtype classification showed significant prognostic outcomes for overall survival (p<.001), cancer-specific survival (p=.003), and recurrence-free survival (p<.05) and remained significant in multivariate analyses that included age at diagnosis, gender, ethnicity, pathologic stage, and histologic grade. A prognostic model was built for overall and recurrence-free survival for non-metastatic ccRCC patients within the context of subtype and clinical characteristics. Conclusions: The ccA and ccB subtypes significantly added prognostic information to clinical parameters, particularly for non-metastatic ccRCC patients.The subtypes can be used for future analyses involving risk for developing metastatic disease and cancer-specific outcomes. This research was supported with a grant from the American Association for Cancer Research, and the UNC Lineberger Comprehensive Cancer Center Cancer Cell Biology Training Grant.

Effect of EH domain containing protein 2 on the biological behavior of clear cell renal cell carcinoma

2019 ◽  
Vol 38 (8) ◽  
pp. 927-937 ◽  
Author(s):  
C Liu ◽  
S Liu ◽  
L Wang ◽  
Y Wang ◽  
Y Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Control Group ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
Eh Domain ◽  
And Migration

To investigate the effects of EH domain containing protein 2 (EHD2) on clear cell renal cell carcinoma (ccRCC) and provide new insights for the clinical treatment of rental cancer. Forty patients (26 males and 14 females, 62.4 ± 5.7 years old) with ccRCC were selected from January 2015 to December 2016 to serve as research subjects in this study. The EHD2 protein expression in the tumor tissues and adjacent healthy tissues of ccRCC patients were detected by Western Blot assay. The cells of ccRCC cell lines RLC-310 and 786-O were divided into normal control group (control), no-load control group (pLV), EHD2 overexpression group (pLV-EHD2), and EHD2 interference group (pLV-siEHD2). The expression levels of EHD2 protein in each group of cells were detected by western blot. The cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. Wound healing assay was performed to check the cell migration ability. Transwell invasion assay was used to detect the cell invasion ability. Cell apoptosis was detected by flow cytometry. The expression level of EHD2 was significantly increased in pLV-EHD2 group and decreased in pLV-siEHD2 group compared with control group and pLV-siEHD2 group, indicating the successfully established EHD2 overexpression cell line and EHD2 RNA interference cell line. EHD2 overexpression enhanced the proliferation, invasion, and migration but inhibited the apoptosis of ccRCC cells, while EHD2 interference showed opposite functions. EHD2 interference can inhibit the development of ccRCC by inhibiting the proliferation, invasion, and migration, and EHD2 can potentially serve as a molecular target for the clinical treatment of ccRCC.

scholarly journals Downregulation of miR-335 exhibited an oncogenic effect via promoting KDM3A/YAP1 networks in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Wenqiang Zhang ◽  
Ruiyu Liu ◽  
Lin Zhang ◽  
Chao Wang ◽  
Ziyan Dong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Survival Rate ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
Downstream Target ◽  
Localized Disease ◽  
And Migration

AbstractClear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer affecting many people worldwide. Although the 5-year survival rate is 65% in localized disease, after metastasis, the survival rate is <10%. Emerging evidence has shown that microRNAs (miRNAs) play a crucial regulatory role in the progression of ccRCC. Here, we show that miR-335, an anti-onco-miRNA, is downregulation in tumor tissue and inhibited ccRCC cell proliferation, invasion, and migration. Our studies further identify the H3K9me1/2 histone demethylase KDM3A as a new miR-335-regulated gene. We show that KDM3A is overexpressed in ccRCC, and its upregulation contributes to the carcinogenesis and metastasis of ccRCC. Moreover, with the overexpression of KDM3A, YAP1 was increased and identified as a direct downstream target of KDM3A. Enrichment of KDM3A demethylase on YAP1 promoter was confirmed by CHIP-qPCR and YAP1 was also found involved in the cell growth and metastasis inhibitory of miR-335. Together, our study establishes a new miR-335/KDM3A/YAP1 regulation axis, which provided new insight and potential targeting of the metastasized ccRCC.

scholarly journals mTORC2 mediate FLCN-induced HIF2α nuclear import and proliferation of clear cell renal cell carcinoma

2020 ◽  
Author(s):  
Xuyang Zhao ◽  
Yadong Ma ◽  
Jie Cui ◽  
Haiyang Zhao ◽  
Lei Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Molecular Mechanism ◽  
Renal Cancer ◽  
Cancer Progression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
And Migration

AbstractClear cell renal cell carcinoma (ccRCC), as the most important type of renal carcinoma, has a high incidence and easy metastasis. Folliculin (FLCN) was identified as a tumor suppressor gene. Its deletions and mutations are associated with a potential risk of kidney cancer. At present, the specific molecular mechanism of FLCN-induced proliferation, invasion and migration in clear cell renal cell carcinoma remains elusive.In this study, we demonstrated that FLCN controled cell proliferation, invasion and migration through PI3K/mTORC2 pathway. FLCN combined with HIF2α in various normal and cancerous renal cells, and mTORC2 mediate FLCN effectively alleviated the deterioration of renal cancer cells by degrading HIF2α. Silencing of FLCN showed promotion of HIF2α protein expression, which in turn led to an increase in downstream target genes Cyclin D1 and MMP9. Moreover, when interfering with siFLCN, HIF2α degradation rate was delayed, and the time of entry into the nucleus was advanced. Taken together, our study illustrated that mTORC2 promoted the specific molecular mechanism of HIF2α by down-regulated FLCN, and might be a new therapeutic target against renal cancer progression.

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