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pmid:34260294
HMGCS2 in metabolic pathways was associated with overall survival in hepatocellular carcinoma: A LASSO-derived study.
Rongrong Ding · Tianyou Chen · Yuan Zhang · Xiaorong Chen · Liping Zhuang · Zongguo Yang
Science progress · 2021 doi:10.1177/00368504211031749
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Experiment
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Complete file
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In the GSE14520, GSE101685, and The Cancer Genome Atlas (TCGA) datasets, differentially expressed genes (DEGs) were identified and functional pathways of common DEGs were enriched. The least absolute shrinkage and selection operator (LASSO) model was used to screen the potential parameters associated with overall survival (OS) in HCC patients. Metabolic pathways were the most significantly enriched functional pathways of common DEGs in these three datasets. After LASSO model analysis, HMGCS2, UGP2, BCLC staging and TNM staging were screened as potential prognostic candidates for OS in HCC patients in GSE14520. HMGCS2 in the metabolic pathway was significantly downregulated in tumor tissues and peripheral blood mononuclear cells in HCC patients (all p < 0.05). Cox regression model indicated that HMGCS2 might be associate with OS in HCC patients in GSE14520 and in the TCGA (p = 0.029 and p = 0.05, respectively). Kaplan-Meier analysis demonstrated that HMGCS2 downregulation in tumors contributed to an unfavorable OS in HCC patients, both in GSE14520 and in the TCGA (p = 0.0001 and p = 0.0002, respectively). Additionally, HMGCS2 was significantly downregulated in HCC patients with high alpha-fetoprotein (AFP), main tumor size >5 cm, multinodular, advanced tumor staging including BCLC, TNM and CLIP (all p < 0.05). 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The combined datasets were available from corresponding authors with reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data availability: Datasets of the current study are available from The Cancer Genome Atlas (https://portal.gdc.cancer.gov/) and the NCBI Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). 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Array"], ["GSE45436", "Hsieh(2013)", "Tissue", "97", "37", "Affymetrix Human Genome U133 Plus 2.0 Array"], ["GSE55092", "Melis et al.(2014)", "Tissue", "49", "91", "Affymetrix Human Genome U133 Plus 2.0 Array"], ["GSE60502", "Kao(2014)", "Tissue", "18", "18", "Affymetrix Human Genome U133A Array"], ["GSE84402", "Qin et al.(2016)", "Tissue", "14", "14", "Affymetrix Human Genome U133 Plus 2.0 Array"], ["GSE101685", "Sen-Yung(2017)", "Tissue", "24", "8", "Affymetrix Human Genome U133 Plus 2.0 Array"], ["GSE58208", "Hui(2014)", "PBMCs", "10", "17", "Affymetrix Human Genome U133 Plus 2.0 Array"], ["GSE49515", "Hui (2013)", "PBMCs", "10", "10", "Affymetrix Human Genome U133 Plus 2.0 Array"], ["TCGA-LIHC", "TCGA", "Tissue", "374", "50", "RNAseq Htseq"]], "row_count": 11, "column_count": 6, "numeric_cells": 47, "header_rows": 1, "locator": "section[4]/table-wrap[1]#table1-00368504211031749"}}, {"id": "asset:table:pmid:34260294:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3ceed7ad53d65801391d4ba2b0f501dac66fb388d33c7a28b7b0d747c87c2960", "bytes": 2841, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#table2-00368504211031749", "version": null, "note": "Significant genes enriched in the top 20 functional pathways.", "structure": {"pmcid": "PMC10358623", "section_index": 11, "section_title": "Common genes identification and enrichment", "row_count": 21, "column_count": 5}, "table": {"label": "Table 2.", "caption": "Significant genes enriched in the top 20 functional pathways.", "rows": [["ID", "Description", "p value", "Adj. p value", "Enriched genes"], ["hsa00280", "Valine, leucine andisoleucine degradation", "0.078", "0.235", "ABAT; EHHADH; ACAT1; ACAA1; AOX1; ECHS1; ALDH6A1; HMGCS2; ALDH2"], ["hsa00380", "Tryptophan metabolism", "0.065", "0.213", "ACAT1; CYP1A2; AOX1; ECHS1; CAT; ALDH8A1; TDO2; ALDH2"], ["hsa05322", "Systemic lupus erythematosus", "0.157", "0.377", "C8A; C8B; C9; C1R; C1S; C6"], ["hsa05150", "Staphylococcus aureus infection", "0.045", "0.196", "CFI; C1R; PLG; C1S"], ["hsa00830", "Retinol metabolism", "0.019", "0.196", "CYP4A11; RDH16; AOX1; CYP2A6; CYP3A4; ADH1C; ADH1A; CYP2C9; CYP2C8; ADH1B"], ["hsa03320", "PPAR signaling pathway", "0.047", "0.196", "ACAA1; CYP4A11; PCK2; ACSL1; HMGCS2; PCK1"], ["hsa05133", "Pertussis", "0.124", "0.33", "CD14; SERPING1; C1R; C1S"], ["hsa04080", "Neuroactiveligand-receptor interaction", "0.269", "0.517", "AGTR1; VIPR1; GHR; PLG"], ["hsa00980", "Metabolism of xenobioticsby cytochrome P450", "0.05", "0.196", "CYP2A6; CYP3A4; ADH1C; ADH1A; CYP2C9; ADH1B; CYP2E1"], ["hsa01100", "Metabolic pathways", "0.001", "0.048", "AGL; CA2; KMO; CYP2C18; GSTZ1; CYP2B6; PEMT; GLUD1; GNE; GBA3; ACSM5; CYP2J2; CYP4F2; EPHX2; ACADSB; GLYAT; GCH1; GLS2; NAT2; BDH2; RGN; ABAT; GNMT; ADH6; GYS2; UGP2; FTCD; EHHADH; HAO1; ALAS1; HAO2; ACAT1; DPYS; CYP1A2; ACAA1; CYP4A11; PCK2; GRHPR; RDH16; AOX1; CYP2A6; ECHS1; CAT; ALDH6A1; ACSL1; FBP1; ALDH8A1; HMGCS2; MAT1A; AKR1D1; NNMT; BHMT; TAT; CYP3A4; TDO2; ALDH2; ADH1C; ADH1A; CYP2C9; ALDOB; ASS1; CYP2C8; PCK1; ADH1B; CYP2E1"], ["hsa05167", "Kaposi sarcoma-associated herpesvirus infection", "0.254", "0.516", "GABARAPL1; RCAN1; FOS; CXCL2"], ["hsa00010", "Glycolysis/gluconeogenesis", "0.053", "0.196", "FBP1; ALDH2; ADH1C; ADH1A; ALDOB; PCK1; ADH1B"], ["hsa04068", "FoxO signaling pathway", "0.117", "0.33", "IGF1; PCK2; CAT; PCK1"], ["hsa00071", "Fatty acid degradation", "0.047", "0.196", "ADH6; EHHADH; ACAT1; ACAA1; CYP4A11; ECHS1; ACSL1; ALDH2; ADH1C; ADH1A; ADH1B"], ["hsa00982", "Drug metabolism—cytochrome P450", "0.025", "0.196", "FMO3; CYP1A2; AOX1; CYP2A6; CYP3A4; ADH1C; ADH1A; CYP2C9; CYP2C8; ADH1B; CYP2E1"], ["hsa03030", "DNA replication", "0.067", "0.213", "PCNA; MCM6; RFC4; MCM3; MCM2; MCM7; RNASEH2A; MCM5; PRIM1; POLE2"], ["hsa04610", "Complement and coagulation cascades", "0.003", "0.079", "C7; KLKB1; CFI; CPB2; C8A; C8B; C9; SERPING1; C1R; PLG; C1S; C6; FGA; F9"], ["hsa05204", "Chemical carcinogenesis", "0.031", "0.196", "ADH6; CYP1A2; CYP2A6; CYP3A4; ADH1C; ADH1A; CYP2C9; CYP2C8; ADH1B; CYP2E1"], ["hsa00650", "Butanoate metabolism", "0.212", "0.463", "BDH2; ABAT; EHHADH; ACAT1; ECHS1; HMGCS2"], ["hsa05146", "Amoebiasis", "0.051", "0.196", "C8A; C8B; C9; CXCL2"]], "row_count": 21, "column_count": 5, "numeric_cells": 67, "header_rows": 1, "locator": "section[11]/table-wrap[1]#table2-00368504211031749"}}, {"id": "asset:table:pmid:34260294:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9447956760cf3d3e28b3dcdfbc7df8d8d06b1f5583fb39bdebc629ff0301c541", "bytes": 1629, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#table3-00368504211031749", "version": null, "note": "Cox regression models for identification of parameters associated with OS in HCC patients in GSE14520 and in the TCGA.", "structure": {"pmcid": "PMC10358623", "section_index": 12, "section_title": "Identification of potential candidates for OS in HCC", "row_count": 25, "column_count": 5}, "table": {"label": "Table 3.", "caption": "Cox regression models for identification of parameters associated with OS in HCC patients in GSE14520 and in the TCGA.", "rows": [["Variables #", "Univariate", "Multivariate"], ["", "HR (95% CI)", "p value", "HR (95% CI)", "p value"], ["GSE14520 dataset"], ["HMGCS2, high versus low", "0.43 (0.27–0.667)", "<0.001", "0.57 (0.34–0.94)", "0.029"], ["UGP2, high versus low", "0.57 (0.37–0.89)", "0.013", "0.95 (0.58–1.56)", "0.844"], ["BCLC staging"], ["0–A", "Reference", "1.0", "Reference", "1.0"], ["B", "2.40 (1.28–4.53)", "0.007", "1.31 (0.61–2.80)", "0.493"], ["C", "4.60 (2.72–7.76)", "<0.001", "2.51 (1.12–5.62)", "0.025"], ["TNM staging"], ["I", "Reference", "1.0", "Reference", "1.0"], ["II", "2.08 (1.21–3.59)", "0.008", "1.87 (1.07–3.27)", "0.027"], ["III", "4.93 (2.82–8.60)", "<0.001", "2.37 (1.04–5.41)", "0.041"], ["TCGA-LIHC dataset*"], ["HMGCS2, high versus low", "0.49 (0.35–0.71)", "<0.001", "0.63 (0.39–1.0)", "0.05"], ["UGP2, high versus low", "0.62 (0.44–0.88)", "0.007", "0.77 (0.49–1.23)", "0.279"], ["AJCC staging"], ["I", "Reference", "1.0", "Reference", "1.0"], ["II", "1.49 (0.91–2.44)", "0.111", "1.27 (0.68–2.36)", "0.454"], ["III", "2.82 (1.85–4.28)", "<0.001", "2.12 (1.25–3.59)", "0.005"], ["IV", "2.64 (1.38–5.04)", "0.003", "2.65 (1.25–5.62)", "0.011"], ["Vascular invasion"], ["None", "Reference", "1.0", "Reference", "1.0"], ["Microvascular", "1.25 (0.80–1.97)", "0.327", "0.96 (0.57–1.60)", "0.873"], ["Macrovascular", "2.24 (1.06–4.72)", "0.034", "1.45 (0.66–3.19)", "0.361"]], "row_count": 25, "column_count": 5, "numeric_cells": 64, "header_rows": 2, "locator": "section[12]/table-wrap[1]#table3-00368504211031749"}}], "gaps": ["asset:data:geo:GSE101685 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