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pmid:36437949
Integrative multiomics evaluation reveals the importance of pseudouridine synthases in hepatocellular carcinoma.
Zhipeng Jin · Mengying Song · Jianping Wang · Wenjing Zhu · Dongxu Sun · Huayuan Liu · Guangjun Shi
Frontiers in genetics · 2022 doi:10.3389/fgene.2022.944681
Paper
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Experiment
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Data
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Analysis
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Complete file
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Here, we assess the roles of PUSs in HCC. Methods: RNA sequencing data of TCGA-LIHC and LIRI-JP were downloaded from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), respectively. GSE36376 gene expression microarray was downloaded from the Gene Expression Omnibus (GEO). Proteomics data for an HBV-related HCC cohort was obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative mRNA expression of genes in clinical tissues and cell lines. Diagnostic efficiency was evaluated by the ROC curve. Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve. Copy number variation (CNV) was analyzed using the GSCA database. Functional analysis was carried out with GSEA, GSVA, and clusterProfiler package. The tumor microenvironment (TME) related analysis was performed using ssGSEA and the ESTIMATE algorithm. Results: We identified 7 PUSs that were significantly upregulated in HCC, and 5 of them (DKC1, PUS1, PUS7, PUSL1, and RPUSD3) were independent risk factors for patients' OS. Meanwhile, the protein expression of DKC1, PUS1, and PUS7 was also upregulated and related to poor survival. Both mRNA and protein of these PUSs were highly diagnostic of HCC. Moreover, the CNV of PUS1, PUS7, PUS7L, and RPUSD2 was also associated with prognosis. Further functional analysis revealed that PUSs were mainly involved in pathways such as genetic information processing, substance metabolism, cell cycle, and immune regulation. 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Methods: RNA sequencing data of TCGA-LIHC and LIRI-JP were downloade"], "order_basis": "paper_text_order:307", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["was obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative", "obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative", "PLEMENTARY TABLE S2Primer sequences used for RT-qPCR. SUPPLEMENTARY TABLE S3Results of differenti", "MENTARY TABLE S2Primer sequences used for RT-qPCR. SUPPLEMENTARY TABLE S3Results of differenti"], "order_basis": "paper_text_order:655", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["Cell Bank (Shanghai, China). The cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM; Hy"], "order_basis": "paper_text_order:2215", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}