scholarly journals The effect of a novel glycolysis-related gene signature on progression, prognosis and immune microenvironment of renal cell carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fangshi Xu ◽  
Yibing Guan ◽  
Li Xue ◽  
Shanlong Huang ◽  
Ke Gao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
Gene Signature ◽  
Related Gene ◽  
Immune Microenvironment ◽  
Risk Genes ◽  
Gene Sets

Abstract Background Glycolysis is a central metabolic pathway for tumor cells. However, the potential roles of glycolysis-related genes in renal cell carcinoma (RCC) have not been investigated. Methods Seven glycolysis-related gene sets were selected from MSigDB and were analyzed through GSEA. Using TCGA database, the glycolysis-related gene signature was constructed. Prognostic analyses were based on the Kaplan–Meier method. The cBioPortal database was employed to perform the mutation analyses. The CIBERSORT algorithm and TIMER database were used to determine the immunological effect of glycolytic gene signature. The expressions in protein level of eight glycolytic risk genes were determined by HPA database. Finally, qPCR, MTT and Transwell invasion assays were conducted to validate the roles of core glycolytic risk genes (CD44, PLOD1 and PLOD2) in RCC. Results Four glycolysis-related gene sets were significantly enriched in RCC samples. The glycolytic risk signature was constructed (including CD44, PLOD2, KIF20A, IDUA, PLOD1, HMMR, DEPDC1 and ANKZF1) and identified as an independent RCC prognostic factor (HR = 1.204). Moreover, genetic alterations of glycolytic risk genes were uncommon in RCC (10.5%) and glycolytic risk signature can partially affect immune microenvironment of RCC. Six glycolytic risk genes (except for IDUA and HMMR) were over-expression in A498 and 786-O renal cancer cells through qPCR test. MTT and Transwell assays revealed that silencing of CD44, PLOD1 and PLOD2 suppressed the proliferation and invasion of renal cancer cells. Conclusions The glycolysis-related risk signature is closely associated with RCC prognosis, progression and immune microenvironment. CD44, PLOD1 and PLOD2 may serve as RCC oncogenes.

Effect of host immunity on metastatic potential in renal cell carcinoma: the assessment of optimal in vivo models to study metastatic behavior of renal cancer cells

Tumor Biology ◽  
2012 ◽  
Vol 33 (2) ◽  
pp. 551-559 ◽  
Author(s):  
Minoru Kobayashi ◽  
Tatsuo Morita ◽  
Nicole A. L. Chun ◽  
Aya Matsui ◽  
Masafumi Takahashi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
Metastatic Potential ◽  
Host Immunity ◽  
In Vivo Models ◽  
Metastatic Behavior

scholarly journals Circular RNA circMTO1 Suppresses RCC Cancer Cell Progression via miR9/LMX1A Axis

2020 ◽  
Vol 19 ◽  
pp. 153303382091428
Author(s):  
Kecheng Li ◽  
Cheng-Liang Wan ◽  
Yan Guo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
Target Genes ◽  
Cell Function ◽  
Circular Rnas ◽  
Promoting Effect

Renal cell carcinoma is one of the most common kidney cancer, which accounts almost 90% of the adult renal malignancies worldwide. In recent years, a new class of endogenous noncoding RNAs, circular RNAs, exert important roles in cell function and certain types of pathological responses, especially in cancers, generally by acting as a microRNA sponge. Circular RNAs could act as sponge to regulate the microRNA and the target genes. However, the knowledge about circular RNAs in renal cell carcinoma remains unclear so far. In the research, we selected a highly expressed novel circular RNAs named circMTO1 in renal cell carcinomas. We investigated the roles of circMTO1 and found that circMTO1 overexpression could suppress cell proliferation and metastases in both A497 and 786-O renal cancer cells, while silencing of circMTO1 could promote the progression in SN12C and OS-RC-2 renal cancer cells. The study showed that circMTO1 acted as miR9 and miR223 sponge and inhibited their levels. Furthermore, silencing of circMTO1 in renal cell carcinoma could downregulate LMX1A, the target of miR-9, resulting in the promotion of renal cell carcinoma cell proliferation and invasion. In addition, LMX1A expression suppression induced by transfection of miR9 mimics confirmed that miR9 exerted its function in renal cell carcinoma by regulating LMX1A expression. What’s more, miR9 inhibitor and LMX1A overexpression could block the tumor-promoting effect of circMTO1 silencing. In conclusion, circMTO1 suppresses renal cell carcinoma progression by circMTO1/miR9/ LMX1A, indicating that circMTO1 may be a potential target in renal cell carcinoma therapy.

scholarly journals Embelin Enhances the Sensitivity of Renal Cancer Cells To Axitinib by Inhibiting HIF-1α Signaling Pathway

2021 ◽  
Author(s):  
Qiong Fang ◽  
Zhiying Li ◽  
Ye Xue ◽  
Xin Zong ◽  
Wenshuang Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
High Recurrence Rate ◽  
Urinary System ◽  
Regulatory Pathways ◽  
Targeted Drug ◽  
Clinical Drugs

Abstract Background Renal cell carcinoma (RCC) is a common malignant tumor of urinary system with high recurrence rate and easy metastasis. Current clinical drugs for renal cell carcinoma include immunotherapy and targeted drugs. Axitinib is a clinical targeted drug for the treatment of renal cell carcinoma, which has some shortcomings such as unstable efficacy and easy drug resistance. The aim of this study was to determine whether embelin can enhance the sensitivity of renal cancer cells to axitinib and explore its regulatory pathways. Results Embelin enhanced the sensitivity of renal cancer cells to axitinib in the following aspects: enhancing the inhibition of cell proliferation by axitinib, the ability to kill cancer cells, and the induction of cell apoptosis. HIF-1α was a potential pathway of Embelin action. After IOX2 regulated the HIF-1α pathway, the enhancing effect of embelin on axitinib was weakened. Conclusions Embelin enhanced the sensitivity of both A498 and 786-O renal cancer cells to axitinib by inhibiting the HIF-1α pathway.

Robustness of the 16-gene signature for prediction of recurrence-free interval in localized clear cell renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 455-455
Author(s):  
Bernard J. Escudier ◽  
Serge Koscielny ◽  
Tara Maddala ◽  
Christer Svedman ◽  
Virginie Verkarre ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Signature ◽  
Stage I ◽  
Rt Pcr ◽  
Cell Renal Cell Carcinoma ◽  
Risk Of Recurrence

455 Background: The Renal Cancer assay is a clinically validated RT-PCR assay developed to estimate the risk of recurrence in stage I-III clear cell renal cell carcinoma (ccRCC) patients (pts) treated with nephrectomy. The assay measures expression of 16 genes that are combined to calculate the Recurrence Score result (RS). The RS is associated with recurrence, renal cancer-specific survival and overall survival (all p<0.001) (Escudier, ASCO 2014). The performance of the RS in clinically relevant subgroups, compared to the Leibovich score, and its within-patient variability was examined. Methods: The algorithm, endpoints, methods, and analysis plan were pre-specified prior to merging clinical and molecular data. RT-PCR of RNA from fixed paraffin-embedded ccRCC tissue was performed without knowledge of clinical data. Recurrence-free internval (RFI) was analyzed using Cox regression stratified by stage with data censored at 5 years, and Kaplan-Meier methods. Multivariable models incorporating the Leibovich score were used to assess the additional contribution of the RS to prediction of recurrence. Within- and between-tumor block reproducibility was assessed in an independent study using two separate tumor blocks from 8 pts, where each block was analyzed at 3 depths. Results: RS was generated in 626/645 pts (97%): 398 stage I, 54 stage II, 174 stage III. Median follow up was 5.5 yrs. The RS was significantly associated with risk of recurrence after adjustment for the Leibovich score (HR=4.20, p<0.001). Additionally, the performance of RS was similar across age groups (<60, 60-70 or ≥70), gender, nephrectomy type, tumor size (≤4, 4-7 or >7cm), grade, and presence/absence of invasion (all interaction p>0.29). Within-patient variability in the score (std. dev. of 1.73 and 4.74 RS units for within- and between-tumor block, respectively) was lower than patient-to-patient variability (std. dev. of 15.6 in validation study). Conclusions: The 16-gene signature remains strongly associated with risk of recurrence after adjustment for the Leibovich score and performs consistently across clinically relevant subgroups. Examination of within-patient and between-patient variability indicates that the score is robust to tumor heterogeneity.

scholarly journals GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism

2019 ◽  
Vol 27 (9) ◽  
pp. 726-738 ◽  
Author(s):  
Qianqian Shi ◽  
Renfang Xu ◽  
Guanglai Song ◽  
Hao Lu ◽  
Dong Xue ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Normal Fibroblast ◽  
Cell Renal Cell Carcinoma ◽  
Renal Cancer Cell

AbstractTumorigenesis and metastasis depend on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. It is, however, unclear regarding the molecular mechanisms underlying the progress and metastasis of human clear-cell renal cell carcinoma in the microenvironment with fibroblasts. In this work, we investigated the effect of normal fibroblasts on the metastasis of renal cancer and the relevant signaling pathways. We isolated normal fibroblasts from normal renal tissues and used normal fibroblast-conditioned medium culture renal cancer cells. The CCK-8 and transwell assays showed that normal fibroblasts conditioned medium significantly enhanced ccRCC cell migration. IL6 mediated the cross talk between normal fibroblasts and the cancer cells, and promoted tumor cell migration through the STAT3 pathway. In contrast, GATA3 was downregulated at both mRNA and protein levels in the normal fibroblast-conditioned medium treated with renal cancer cells, but upregulated in adjacent normal tissues. GATA3 overexpression significantly reduced STAT3 phosphorylation and attenuated the migration in both renal cancer cell and IL6-stimulated renal cancer cell. Taken together, our findings suggest that the IL6/STAT3 pathway plays a crucial role in the normal fibroblast-enhanced clear-cell renal cell carcinoma metastasis, while GATA3 may mitigate this effect by inhibiting IL6/STAT3 signaling.

scholarly journals Identification of a Novel Glycolysis-Related Gene Signature Correlates With the Prognosis and Therapeutic Responses in Patients With Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhengtong Lv ◽  
Lin Qi ◽  
Xiheng Hu ◽  
Miao Mo ◽  
Huichuan Jiang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Gene Signature ◽  
Human Protein ◽  
Related Gene ◽  
Cell Renal Cell Carcinoma ◽  
Human Protein Atlas

BackgroundAccumulating evidences indicate significant alterations in the aerobic glycolysis in clear cell renal cell carcinoma (ccRCC). We aim to develop and validate a glycolysis-related genes signature for predicting the clinical outcomes of patients with ccRCC.MethodsmRNA expression profiling of ccRCC was obtained from The Cancer Genome Atlas database. Univariate Cox regression analysis and lasso Cox regression model were performed to identify and construct the prognostic gene signature. The protein expression levels of the core genes were obtained from the Human Protein Atlas database. We used four external independent data sets to verify the predictive power of the model for prognosis, tyrosine kinase inhibitor (TKI) therapy, and immunotherapy responses, respectively. Finally, we explored the potential mechanism of this signature through gene set enrichment analysis (GSEA).ResultsThrough the GSEA, glycolysis-related gene sets were significantly different between ccRCC tissues and normal tissues. Next, we identified and constructed a seven-mRNA signature (GALM, TGFA, RBCK1, CD44, HK3, KIF20A, and IDUA), which was significantly correlated with worse survival outcome and was an independent prognostic indicator for ccRCC patients. Furthermore, the expression levels of hub genes were validated based on the Human Protein Atlas databases. More importantly, the model can predict patients’ response to TKI therapy and immunotherapy. These findings were successfully validated in the external independent ccRCC cohorts. The mechanism exploration showed that the model may influence the prognosis by influencing tumor proliferation, base mismatch repair system and immune status of patients.ConclusionsOur study has built up a robust glycolysis-based molecular signature that predicts the prognosis and TKI therapy and immunotherapy responses of patients with ccRCC with high accuracy, which might provide important guidance for clinical assessment. Also, clinical investigations in large ccRCC cohorts are greatly needed to validate our findings.

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