1.Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma.
Wanting HOU ; Qiulin TANG ; Feng BI
Journal of Biomedical Engineering 2019;36(2):267-273
To evaluate the differential expression profiles of the lncRNAs, miRNAs, mRNAs and ceRNAs, and their implication in the prognosis in clear cell renal cell carcinoma (CCRCC), the large sample genomics analysis technologies were used in this study. The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas (TCGA) database, and R software was used for gene expression analysis and survival analysis. Cytoscape software was used to construct the ceRNA network. The results showed that a total of 1 570 lncRNAs, 54 miRNAs, and 17 mRNAs were differentially expressed in CCRCC, and most of their expression levels were up-regulated (false discovery rate < 0.01 and absolute log fold change > 2). The ceRNA regulatory network showed the interaction between 89 differentially expressed lncRNAs and 9 differentially expressed miRNAs. Further survival analysis revealed that 38 lncRNAs (including COL18A1-AS1, TCL6, LINC00475, UCA1, WT1-AS, HOTTIP, PVT1, etc.) and 2 miRNAs (including miR-21 and miR-155) were correlated with the overall survival time of CCRCC ( < 0.05). Together, this study provided us several new evidences for the targeted therapy and prognosis assessment of CCRCC.
Carcinoma, Renal Cell
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genetics
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Humans
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Kidney Neoplasms
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genetics
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MicroRNAs
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genetics
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RNA, Long Noncoding
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genetics
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Transcriptome
4.Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma.
Jin-Shuai GUO ; Hao DING ; Peng-Yu WU ; Zi-Yi XIN ; Jian-Xin LI ; Hyon-Su JO ; Zhen-Hai MA
Chinese Medical Sciences Journal 2023;38(3):191-205
Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.
Humans
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Carcinoma, Renal Cell/genetics*
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Immunotherapy
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Kidney
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Kidney Neoplasms/genetics*
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Prognosis
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Copper
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Apoptosis
5.Establishment of a mutation prediction model for evaluating the efficacy of immunotherapy in renal carcinoma.
Cai Peng QIN ; Yu Xuan SONG ; Meng Ting DING ; Fei WANG ; Jia Xing LIN ; Wen Bo YANG ; Yi Qing DU ; Qing LI ; Shi Jun LIU ; Tao XU
Journal of Peking University(Health Sciences) 2022;54(4):663-668
OBJECTIVE:
To establish a mutation prediction model for efficacy assessment, the genomic sequencing data of renal cancer patients from the MSKCC (Memorial Sloan Kettering Cancer Center) pan-cancer immunotherapy cohort was used.
METHODS:
The genomic sequencing data of 121 clear cell renal cell carcinoma patients treated with immune checkpoint inhibitors (ICI) in the MSKCC pan-cancer immunotherapy cohort were obtained from cBioPortal database (http://www.cbioportal.org/) and they were analyzed by univariate and multivariate Cox regression analysis to identify mutated genes associated with ICI treatment efficacy, and we constructed a comprehensive prediction model for drug efficacy of ICI based on mutated genes using nomogram. Survival analysis and time-dependent receiver operator characteristic curves were performed to assess the prognostic value of the model. Transcriptome and genomic sequencing data of 538 renal cell carcinoma patients were obtained from the TCGA database (https://portal.gdc.cancer.gov/). Gene set enrichment analysis was used to identify the potential functions of the mutated genes enrolled in the nomogram.
RESULTS:
We used multivariate Cox regression analysis and identified mutations in PBRM1 and ARID1A were associated with treatment outcomes in the patients with renal cancer in the MSKCC pan-cancer immunotherapy cohort. Based on this, we established an efficacy prediction model including age, gender, treatment type, tumor mutational burden (TMB), PBRM1 and ARID1A mutation status (HR=4.33, 95%CI: 1.42-13.23, P=0.01, 1-year survival AUC=0.700, 2-year survival AUC=0.825, 3-year survival AUC=0.776). The validation (HR=2.72, 95%CI: 1.12-6.64, P=0.027, 1-year survival AUC=0.694, 2-year survival AUC=0.709, 3-year survival AUC=0.609) and combination (HR=2.20, 95%CI: 1.14-4.26, P=0.019, 1-year survival AUC=0.613, 2-year survival AUC=0.687, 3-year survival AUC=0.526) sets confirmed these results. Gene set enrichment analysis indicated that PBRM1 was involved in positive regulation of epithelial cell differentiation, regulation of the T cell differentiation and regulation of humoral immune response. In addition, ARID1A was involved in regulation of the T cell activation, positive regulation of T cell mediated cyto-toxicity and positive regulation of immune effector process.
CONCLUSION
PBRM1 and ARID1A mutations can be used as potential biomarkers for the evaluation of renal cancer immunotherapy efficacy. The efficacy prediction model established based on the mutation status of the above two genes can be used to screen renal cancer patients who are more suitable for ICI immunotherapy.
Biomarkers, Tumor/genetics*
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Carcinoma, Renal Cell/therapy*
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Humans
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Immunotherapy/methods*
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Kidney Neoplasms/therapy*
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Mutation
6.Consensus on clinical diagnosis and treatment of fumarate hydratase-deficient renal cell carcinoma.
Chinese Journal of Surgery 2022;60(11):961-968
Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is an independent pathological subtype of renal cell carcinoma with a clear driver gene and a high degree of malignancy. Recent studies have found that patients with somatic FH mutations have similar clinico-biological behavior and poor prognosis to patients with germline FH mutations. FH-RCC has the characteristics of early age of onset, atypical imaging manifestations, variable pathological patterns, difficult clinical diagnosis and poor effect on traditional drug treatment, thus greatly endangering the life and health of patients. Under the organization of the Rare Kidney Cancer Collaborative Group, Genitourinary Cancer Committee, China Anti-Cancer Association, this guideline was developed based on basic research, clinical cohort and evidence-based medicine evidence, including imaging manifestations, pathological diagnosis, genetic testing, surgical and systemic treatment options, and provided recommendations and references for the diagnosis and treatment norms.
Humans
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Carcinoma, Renal Cell/therapy*
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Fumarate Hydratase/genetics*
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Consensus
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Kidney Neoplasms/therapy*
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Immunohistochemistry
8.MiR-744-5p inhibits the proliferation, invasion, and migration of clear-cell renal cell carcinoma cells by targeting CCND1.
Kun Yang LEI ; Wen Jie XIE ; Ting SUN ; Yi Fu LIU ; Xu WANG
Journal of Southern Medical University 2022;42(5):712-717
OBJECTIVE:
To explore the role of miR-744-5p/CCND1 axis in clear-cell renal cell carcinoma (ccRCC).
METHODS:
We examined the expression levels of miR-744-5p in 65 pairs of ccRCC and adjacent tissue specimens and in 5 ccRCC cell lines and human renal tubular epithelial (HK2) cells using qRT-PCR. The ccRCC cell lines 786-O and OSRC2 were transfected with miR-744-5p mimic, CCND1 mimic, or their negative control mimics, and the changes in cell proliferation, migration, and invasion were evaluated with CCK-8, wound healing, and Transwell assays. The downstream target molecules of miR-744-5p were predicted by bioinformatics analysis, and the expression level of CCND1 in ccRCC cells was verified by qRT-PCR and Western blotting. The relationship between miR-744-5p and CCND1 was further validated by dual luciferase reporter assay, and the role of the miR-744-5p/CCND1 axis in ccRCC was explored by rescue experiments.
RESULTS:
MiR-744-5p was significantly downregulated in ccRCC tissues and cell lines (all P < 0.05), and its overexpression inhibited the proliferation, migration, and invasion of ccRCC cells (all P < 0.05). Bioinformatics analysis and dual luciferase reporter assay showed that CCND1 was a downstream target of miR-744-5p. The results of rescue experiments showed that upregulation of CCND1 could partially reverse the inhibitory effect of miR-744-5p overexpression on ccRCC cell proliferation, migration, and invasion (all P < 0.05).
CONCLUSION
MiR-744-5p inhibits the malignant phenotype of ccRCC cells by targeting CCND1, and the miR-744-5p/CCND1 axis may be a novel target for diagnosis and treatment of ccRCC.
Carcinoma, Renal Cell/metabolism*
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Cell Line, Tumor
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Cell Movement/genetics*
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Cell Proliferation/genetics*
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Cyclin D1/genetics*
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Humans
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Kidney Neoplasms/metabolism*
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MicroRNAs/metabolism*
9.Pathologic diagnosis of renal neoplasm.
Chinese Journal of Pathology 2008;37(11):775-779
10.Clinical analysis in diagnosis and treatment of 11 patients with hereditary renal cell carcinoma.
Da-xin GONG ; Xia WANG ; Ze-liang LI ; Yuan-jun JIANG ; Zhi-xi SUN ; Chui-ze KONG
Chinese Journal of Surgery 2006;44(14):963-965
OBJECTIVETo evaluate the diagnosis and treatment of hereditary renal cell carcinoma.
METHODSClinical data of 11 patients with hereditary renal cell carcinoma were analyzed retrospectively. Eight patients were male and 3 were female, age ranged from 32 to 67 (mean: age 48 years). Four cases were bilateral renal cell carcinoma, and 4 were multiple renal cell carcinoma. Two cases were diagnosed as Von Hippel-Lindau syndrome, 6 as familial clear cell renal cell cancer, and 3 as hereditary papillary renal carcinoma.
RESULTSTen patients performed nephron-sparing surgery and/or radical nephrectomy and 1 had no operation. The patients were followed up from 12 to 114 months. Tumor recurrence was observed in 4 patients, 1 patient died of tumor metastasis, and 2 died of other causes. Four patients survived free of tumor.
CONCLUSIONSHereditary renal carcinoma appears in the youth, and it is predominantly multiple and bilateral. Nephron-sparing surgery is the standard method of treatment for the patients.
Adult ; Aged ; Carcinoma, Renal Cell ; diagnosis ; genetics ; surgery ; Female ; Humans ; Kidney Neoplasms ; diagnosis ; genetics ; surgery ; Male ; Middle Aged ; Retrospective Studies