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pmid:33154194

Three-gene risk model in papillary renal cell carcinoma: a robust likelihood-based survival analysis.

Yutao Wang · Kexin Yan · Jiaxing Lin · Jianfeng Wang · Zhenhua Zheng · Xinxin Li · Zhixiong Hua · Yuepeng Bu · Jianxiu Shi · Siqing Sun · Xuejie Li · Yang Liu · Jianbin Bi

Aging · 2020 doi:10.18632/aging.104001

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33154194
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title
Three-gene risk model in papillary renal cell carcinoma: a robust likelihood-based survival analysis.
doi
10.18632/aging.104001
pmid
33154194
authors array · 13 items
[0]
Yutao Wang
[1]
Kexin Yan
[2]
Jiaxing Lin
[3]
Jianfeng Wang
[4]
Zhenhua Zheng
[5]
Xinxin Li
[6]
Zhixiong Hua
[7]
Yuepeng Bu
[8]
Jianxiu Shi
[9]
Siqing Sun
[10]
Xuejie Li
[11]
Yang Liu
[12]
Jianbin Bi
journal
Aging
year
2020
abstract
BACKGROUND: Papillary renal cell carcinoma (PRCC) accounts for 15% of all renal cell carcinomas. The molecular mechanisms of renal papillary cell carcinoma remain unclear, and treatments for advanced disease are limited. RESULT: We built the computing model as follows: Risk score = 1.806 * TPX2 - 0.355 * TXNRD2 - 0.805 * SLC6A20. The 3-year AUC of overall survival was 0.917 in the training set (147 PRCC samples) and 0.760 in the test set (142 PRCC samples). Based on the robust model, M2 macrophages showed positive correlation with risk score, while M1 macrophages were the opposite. PRCC patients with low risk score showed higher tumor mutation burden. TPX2 is a risk factor, and co-expression factors were enriched in cell proliferation and cancer-related pathways. Finally, the proliferation and invasion of PRCC cell line were decreased in the TPX2 reduced group, and the differential expression was identified. TPX2 is a potential risk biomarker which involved in cell proliferation in PRCC. CONCLUSION: We conducted a study to develop a three gene model for predicting prognosis in patients with papillary renal cell carcinoma. Our findings may provide candidate biomarkers for prognosis that have important implications for understanding the therapeutic targets of papillary renal cell carcinoma. METHOD: Gene expression matrix and clinical data were obtained from TCGA (The Cancer Genome Atlas), GSE26574, GSE2048, and GSE7023. Prognostic factors were identified using "survival" and "rbsurv" packages, and a risk score was constructed using Multivariate Cox regression analysis. The co-expression networks of the factors in model were constructed using the "WGCNA" package. The co-expression genes of factors were enriched and displayed the biological process. Based on this robust risk model, immune cells infiltration proportions and tumor mutation burdens were compared between risk groups. Subsequently, using the PRCC cell line, the role of TPX2 was determined by Cell proliferation assay, 5-Ethynyl-20-deoxyuridine assay and Transwell assay.
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The expression matrix and clinical information of renal papillary cell carcinoma were obtained from TCGA (http://cancergenome.nih.gov/). We obtained the expression matrix and platform comment information of GSE26574 [27], GSE7023 [28], GSE 2748 [29] from the GEO Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/). The “Survival” package [30] was used to obtain prognostic factors.
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The expression matrix and clinical information of renal papillary cell carcinoma were obtained from TCGA (http://cancergenome.nih.gov/).
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We obtained the expression matrix and platform comment information of GSE26574 [27], GSE7023 [28], GSE 2748 [29] from the GEO Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/).
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The “Survival” package [30] was used to obtain prognostic factors.
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The expression matrix and clinical information of renal papillary cell carcinoma were obtained from TCGA (http://cancergenome.nih.gov/).
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Robust prognostic gene selection
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Univariate regression analyses of prognostic factors for overall survival.
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Robust prognostic gene selection
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quote
The expression matrix and clinical information of renal papillary cell carcinoma were obtained from TCGA (http://cancergenome.nih.gov/). We obtained the expression matrix and platform comment information of GSE26574 [27], GSE7023 [28], GSE 2748 [29] from the GEO Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/). The “Survival” package [30] was used to obtain prognostic factors.
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cancer in 33 cancer types. Cell culture and siRNA-PTEN construction The SKRC39 cells were cult
[1]
ed at 37 °C, with 5% CO2. The TPX2 (H) - 951 siRNA sequences were as follows: 5’-CCUGUAAUCAUCGA
[2]
UUCAUCGAUGAUUACAGGTT-3’. The TPX2 (H) - 2046 siRNA sequences were: 5’-GCUCAACCUGUGCCACAUUTT-3’
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The expression matrix and clinical information of renal papillary cell carcinoma were obtained from TCGA (http://cancergenome.nih.gov/). We obtained the expression matrix and platform comment information of GSE26574 [27], GSE7023 [28], GSE 2748 [29] from the GEO Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/). The “Survival” package [30] was used to obtain prognostic factors.
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Complete file
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The molecular mechanisms of renal papillary cell carcinoma remain unclear, and treatments for advanced disease are limited.\nRESULT: We built the computing model as follows: Risk score = 1.806 * TPX2 - 0.355 * TXNRD2 - 0.805 * SLC6A20. The 3-year AUC of overall survival was 0.917 in the training set (147 PRCC samples) and 0.760 in the test set (142 PRCC samples). Based on the robust model, M2 macrophages showed positive correlation with risk score, while M1 macrophages were the opposite. PRCC patients with low risk score showed higher tumor mutation burden. TPX2 is a risk factor, and co-expression factors were enriched in cell proliferation and cancer-related pathways. Finally, the proliferation and invasion of PRCC cell line were decreased in the TPX2 reduced group, and the differential expression was identified. TPX2 is a potential risk biomarker which involved in cell proliferation in PRCC.\nCONCLUSION: We conducted a study to develop a three gene model for predicting prognosis in patients with papillary renal cell carcinoma. Our findings may provide candidate biomarkers for prognosis that have important implications for understanding the therapeutic targets of papillary renal cell carcinoma.\nMETHOD: Gene expression matrix and clinical data were obtained from TCGA (The Cancer Genome Atlas), GSE26574, GSE2048, and GSE7023. Prognostic factors were identified using \"survival\" and \"rbsurv\" packages, and a risk score was constructed using Multivariate Cox regression analysis. The co-expression networks of the factors in model were constructed using the \"WGCNA\" package. The co-expression genes of factors were enriched and displayed the biological process. Based on this robust risk model, immune cells infiltration proportions and tumor mutation burdens were compared between risk groups. Subsequently, using the PRCC cell line, the role of TPX2 was determined by Cell proliferation assay, 5-Ethynyl-20-deoxyuridine assay and Transwell assay.", "claims": [{"id": "claim-method", "statement": "The expression matrix and clinical information of renal papillary cell carcinoma were obtained from TCGA (http://cancergenome.nih.gov/). We obtained the expression matrix and platform comment information of GSE26574 [27], GSE7023 [28], GSE 2748 [29] from the GEO Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/). 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE26574"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE26574"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33154194", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.104001", "sha256": 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The “Survival” package [30] was used to obtain prognostic factors."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Cell culture and siRNA-PTEN construction The SKRC39 cells were cult", "ed at 37 °C, with 5% CO2. The TPX2 (H) - 951 siRNA sequences were as follows: 5’-CCUGUAAUCAUCGA", "UUCAUCGAUGAUUACAGGTT-3’. The TPX2 (H) - 2046 siRNA sequences were: 5’-GCUCAACCUGUGCCACAUUTT-3’"], "order_basis": "paper_text_order:2415", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The expression matrix and clinical information of renal papillary cell carcinoma were obtained from TCGA (http://cancergenome.nih.gov/). We obtained the expression matrix and platform comment information of GSE26574 [27], GSE7023 [28], GSE 2748 [29] from the GEO Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/). The “Survival” package [30] was used to obtain prognostic factors."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}