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pmid:29138825
Utility of miR‑133a‑3p as a diagnostic indicator for hepatocellular carcinoma: An investigation combined with GEO, TCGA, meta‑analysis and bioinformatics.
Hai-Wei Liang · Xia Yang · Dong-Yue Wen · Li Gao · Xiang-Yu Zhang · Zhi-Hua Ye · Jie Luo · Zu-Yun Li · Yun He · Yu-Yan Pang · Gang Chen
Molecular medicine reports · 2018 doi:10.3892/mmr.2017.8040
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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In the present study, the diagnostic role of miR‑133a‑3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA). Published studies reporting the association between miR‑133a‑3p expression and HCC were reviewed from multiple databases. By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR‑133a‑3p expression and clinicopathological features of HCC. Eventually, putative targets of miR‑133a‑3p in HCC were selected for further bioinformatics prediction. A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR‑133a‑3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=‑0.54; 95% confidence interval (CI), ‑0.74 to ‑0.35; P<0.001]. Consistently, the level of miR‑133a‑1 in HCC was reduced markedly compared to normal tissues (P<0.001) based on TCGA data, and the AUC value of low miR‑133a‑1 expression for HCC diagnosis was 0.670 (P<0.001). Furthermore, the combined SMD of all datasets (GEO, TCGA and literature) suggested that significant difference was observed between the HCC group and the normal control group, and lower miR‑133a‑3p expression in HCC group was noted (SMD=‑0.69; 95% CI, ‑1.10 to ‑0.29; P=0.001). In addition, the authors discovered five key genes of the calcium signaling pathway (NOS1, ADRA1A, ADRA1B, ADRA1D and TBXA2R) that may probably be targeted by miR‑133a‑3p in HCC. The study reveals that miR‑133a‑3p may function as a tumor suppressor in HCC. The prospective novel pathways and key genes of miR‑133a‑3p could offer potential biomarkers for HCC; however, the predictions require further confirmation.", "claims": [{"id": "claim-method", "statement": "Student's t-test was applied to verify the difference between two corresponding groups of various clinical features.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29138825", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "Student's t-test was applied to verify the difference between two corresponding groups of various clinical features."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors first searched GEO datasets to assess the expression of miR-133a-3p between HCC and non-cancer tissues. miR-133a-3p levels in eight datasets GSE57555 (Japan), GSE69580 (Taiwan), GSE54751 (USA), GSE41874 (Japan), GSE40744 (USA), GSE21362 (Japan), GSE22058 (USA) and GSE12717 (USA) which included 217 HCC and 219 normal tissues are presented in Fig. 3.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29138825", "locator": "sections[16] \"Signatures of GEO datasets and meta-analysis\" paragraph 2", "quote": "The authors first searched GEO datasets to assess the expression of miR-133a-3p between HCC and non-cancer tissues. miR-133a-3p levels in eight datasets GSE57555 (Japan), GSE69580 (Taiwan), GSE54751 (USA), GSE41874 (Japan), GSE40744 (USA), GSE21362 (Japan), GSE22058 (USA) and GSE12717 (USA) which included 217 HCC and 219 normal tissues are presented in Fig. 3."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A meta-analysis combining GEO microarray, TCGA, and published-study data found that miR-133a-3p expression was lower in HCC tissues than in normal tissues (SMD = −0.54; 95% CI, −0.74 to −0.35; P<0.001).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR-133a-3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=−0.54; 95% confidence interval (CI), −0.74 to −0.35; P<0.001]."}, "evidence": [{"asset": "source:pmid:29138825", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR-133a-3p expression and clinicopathological features of HCC."}, {"asset": "source:pmid:29138825", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR-133a-3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=−0.54; 95% confidence interval (CI), −0.74 to −0.35; P<0.001]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A meta-analysis combining GEO microarray, TCGA, and published-study data found that miR-133a-3p expression was lower in HCC tissues than in normal tissues (SMD = −0.54; 95% CI, −0.74 to −0.35; P<0.001).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:29138825"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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(publication)", "Country", "<60", "≥60", "Male", "Female", "HCC", "Normal control", "HCC", "Normal"], ["GSE57555", "2015", "Japan", "6", "15", "18", "3", "5", "16", "−0.042±0.006", "−0.053±0.018"], ["GSE69580", "2015", "Taiwan", "–", "–", "–", "–", "5", "5", "1.854±1.106", "1.697±0.937"], ["GSE54751", "2014", "USA", "6", "14", "10", "10", "13", "7", "0.001±0.001", "0.005±0.009"], ["GSE41874", "2013", "Japan", "9", "0", "6", "3", "6", "4", "1.032±0.206", "1.043±0.346"], ["GSE40744", "2013", "USA", "16", "5", "15", "6", "9", "12", "1.741±0.171", "1.862±0.247"], ["GSE21362", "2011", "Japan", "–", "–", "–", "–", "73", "73", "2.632±1.514", "3.316±1.571"], ["GSE22058", "2010", "USA", "–", "–", "–", "–", "96", "96", "−0.746±0.369", "−0.530±0.216"], ["GSE12717", "2008", "USA", "16", "0", "4", "12", "10", "6", "6.475±1.395", "7.997±0.219"], ["Zhang et al", "2015", "China", "–", "–", "24", "16", "40", "40", "0.510±0.110", "1.050±0.240"], ["PCR", "2016", "China", "–", "–", "75", "20", "95", "95", "3.285±2.379", "4.497±2.195"], ["TCGA", "–", "–", "172", "204", "255", "122", "367", "50", "3.484±1.928", "4.444±1.116"]], "row_count": 14, "column_count": 11, "numeric_cells": 92, "header_rows": 3, "locator": "section[18]/table-wrap[1]#tI-mmr-17-01-1469"}}, {"id": "asset:table:pmid:29138825:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b1c0db4a01dc2067c5d47a236416466f4b7d70785e834110d440e5e37f53c149", "bytes": 5138, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[21]/table-wrap[1]#tII-mmr-17-01-1469", "version": null, "note": "GO functional annotation for most significantly related targets of miR133a-3p.", "structure": {"pmcid": "PMC5780086", "section_index": 21, "section_title": "Targets prediction and functional enrichment", "row_count": 34, "column_count": 7}, "table": {"label": "Table II.", "caption": "GO functional annotation for most significantly related targets of miR133a-3p.", "rows": [["GO ID", "GO term", "Count (%)", "P-value", "Benjamini", "FDR", "Genesa"], ["Biological process"], ["GO:0007267", "Cell-cell signaling", "70 (0.9)", "2.24×10−12", "6.42E-09", "4.02E-09", "SYT1, PDGFA, SLC6A2, SLC6A4, EFNA3, LPAR3, ILDR2, GABBR2, ENPEP, GJA5"], ["GO:0007268", "Synaptic transmission", "40 (0.5)", "4.78×10−9", "6.83E-06", "8.56E-06", "PPFIA3, SYT1, RAB3A, SLC6A2, OPRK1, SLC6A4, LPAR3, OXTR, GABBR2, DFNB31"], ["GO:0019226", "Transmission of nerve", "43 (0.6)", "1.63×10−8", "1.55E-05", "2.91E-05", "PPFIA3, SYT1, RAB3A, SLC6A2, OPRK1, SLC6A4, LPAR3, OXTR, GABBR2, DFNB31"], ["GO:0048666", "Neuron development", "41 (0.6)", "5.71×10−8", "4.08E-05", "1.02E-04", "RAB3A, CDK5R1, PAX2, CXCL12, EPHB1, EPHB2, TGFB2, DFNB31, LINGO1, BDNF"], ["GO:0030182", "Neuron differentiation", "47 (0.6)", "1.99×10−7", "1.14E-04", "3.57E-04", "RAB3A, CDK5R1, NNAT, BRSK1, PAX2, CXCL12, EPHB1, TGFB2, EPHB2, DFNB31"], ["GO:0000902", "Cell morphogenesis", "41 (0.6)", "2.17×10−7", "1.04E-04", "3.90E-04", "RAB3A, CDK5R1, TFCP2L1, BRSK1, SOX6, SOX9, PAX2, CXCL12, EPHB1, EPHB2"], ["GO:0031175", "Neuron projection", "33 (0.4)", "3.37×10−7", "1.38E-04", "6.04E-04", "RAB3A, CDK5R1, PAX2, CXCL12, EPHB1, EPHB2, LINGO1, BDNF, PVRL1, ANK3"], ["GO:0000904", "Cell morphogenesis", "32 (0.4)", "3.62×10−7", "1.29E-04", "6.48E-04", "RAB3A, CDK5R1, SOX9, PAX2, CXCL12, EPHB1, EPHB2, TGFB2, BDNF, PVRL1"], ["GO:0030030", "Cell projection", "41 (0.6)", "5.20×10−7", "1.65E-04", "9.32E-04", "RAB3A, CDK5R1, CROCC, PDGFA, LPAR3, PAX2, CXCL12, EPHB1, EPHB2, DFNB31"], ["GO:0048667", "Cell morphogenesis involved", "28 (0.4)", "1.48×10−6", "4.23E-04", "0.002647", "RAB3A, CDK5R1, PAX2, CXCL12, EPHB1, EPHB2, BDNF, PVRL1, ANK3, BAI1"], ["Cellular component"], ["GO:0044459", "Plasma membrane part", "176 (2.4)", "1.74×10−13", "6.66E-11", "2.42E-10", "SYT1, ENAH, ADORA3, SGMS2, SLC6A20, SLC6A2, SYT2, EFNA3, SYT3, SLC6A4"], ["GO:0005887", "Integral to plasma", "108 (1.5)", "2.56×10−11", "4.88E-09", "3.54E-08", "ADORA3, SGMS2, SLC6A20, SLC6A2, SLC6A4, EFNA3, SLC7A8, CSPG4, LPAR3, ENPEP"], ["GO:0031226", "Intrinsic to plasma", "109 (1.5)", "4.46×10−11", "5.68E-09", "6.18E-08", "ADORA3, SGMS2, SLC6A20, SLC6A2, SLC6A4, EFNA3, SLC7A8, CSPG4, LPAR3, ENPEP"], ["GO:0005886", "Plasma membrane", "239 (3.2)", "7.37×10−8", "7.04E-06", "1.02E-04", "SYT1, ADORA3, GLDN, SGMS2, SYT2, EFNA3, SYT3, LPAR3, SYT9, SYP"], ["GO:0045202", "Synapse", "40 (0.5)", "7.75×10−7", "5.92E-05", "0.001073", "RAB3A, SYT1, CDK5R1, ENAH, RAB3B, LZTS1, RAB3C, SYT2, SYT3, SYT9"], ["GO:0016021", "Integral to membrane", "299 (4.0)", "3.61×10−5", "0.002295", "0.049989", "CYP3A4, SYT1, ADORA3, SGMS2, GLDN, SYT2, SLC9A2, EFNA3, SYT3, SYT9"], ["GO:0034702", "Ion channel complex", "25 (0.3)", "3.75×10−5", "0.002043", "0.051895", "KCNA3, CACNB3, KCNJ14, KCNJ13, TTYH3, KCNQ4, BEST1, TTYH2, KCNE1, CHRFAM7A"], ["GO:0031224", "Intrinsic to membrane", "307 (4.1)", "5.18×10−5", "0.002469", "0.071712", "CYP3A4, SYT1, ADORA3, SGMS2, GLDN, SYT2, SLC9A2, SYT3, EFNA3, SYT9"], ["GO:0030054", "Cell junction", "46 (0.6)", "5.59×10−5", "0.002369", "0.077386", "SYT1, ENAH, LZTS1, SYT2, SYT3, FERMT1, SYT9, OXTR, BRSK1, GABBR2"], ["GO:0043005", "Neuron projection", "34 (0.5)", "7.87×10−5", "0.003003", "0.109018", "SYT1, CDK5R1, LZTS1, TACR1, GABBR2, KLC2, TGFB2, DFNB31, PCSK1, KCNQ4"], ["Molecular function"], ["GO:0005509", "Calcium ion binding", "73 (1.0)", "9.04×10−6", "0.007564", "0.013963", "SYT1, LDLR, MASP1, SYT2, MMP9, SYT3, SYT9, ENPEP, PCDHGA4, MMP3"], ["GO:0004935", "Adrenoceptor activity", "6 (0.1)", "4.55×10−5", "0.018938", "0.070301", "ADRB1, HTR4, ADRA1B, ADRA1A, ADRA2B, ADRA1D"], ["GO:0005003", "Ephrin receptor activity", "7 (0.1)", "8.10×10−5", "0.022426", "0.125062", "EPHA7, EFNB3, EFNA3, EPHA10, EFNA4, EPHB1, EPHB2"], ["GO:0022832", "Voltage-gated channel activity", "23 (0.3)", "1.16×10−4", "0.024163", "0.179776", "HCN2, KCND3, CACNA1I, CACNG4, KCNA3, KCNJ10, CACNB3, KCNK13, KCNJ14, KCTD7"], ["GO:0005244", "Voltage-gatedion channel activity", "23 (0.3)", "1.16×10−4", "0.024163", "0.179776", "HCN2, KCND3, CACNA1I, CACNG4, KCNA3, KCNJ10, CACNB3, KCNK13, KCNJ14, KCTD7"], ["GO:0022843", "Voltage-gatedcation channel activity", "19 (0.3)", "1.71×10−4", "0.02837", "0.264299", "HCN2, KCND3, CACNA1I, CACNG4, KCNA3, KCNJ10, CACNB3, KCNJ14, KCTD7, KCNJ13"], ["GO:0005261", "Cation channel activity", "28 (0.4)", "2.23×10−4", "0.030778", "0.344365", "KCNA3, KCNJ10, CACNB3, KCNK13, KCNJ14, KCNK10, KCNJ13, KCNQ4, GPM6A, KCNE"], ["GO:0015267", "Channel activity", "37 (0.5)", "2.31×10−4", "0.027299", "0.355692", "KCNA3, KCNJ10, CACNB3, KCNK13, GJA5, KCNJ14, KCNK10, KCNJ13, MIP, TTYH3"], ["GO:0022803", "Passive transmembrane transporter activity", "37 (0.5)", "2.41×10−4", "0.024983", "0.371552", "KCNA3, KCNJ10, CACNB3, KCNK13, GJA5, KCNJ14, KCNK10, KCNJ13, MIP, TTYH3"], ["GO:0022838", "Substrate specific channel activity", "36 (0.5)", "2.48×10−4", "0.022846", "0.3818", "KCNA3, KCNJ10, CACNB3, KCNK13, KCNJ14, KCNK10, KCNJ13, MIP, TTYH3, KCNQ4"]], "row_count": 34, "column_count": 7, "numeric_cells": 172, "header_rows": 1, "locator": "section[21]/table-wrap[1]#tII-mmr-17-01-1469"}}, {"id": "asset:table:pmid:29138825:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:036e02d3335dbff9940a5f30e1d55bbd1a4896478bf73d4bc058d0222d573a0e", "bytes": 3166, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[21]/table-wrap[2]#tIII-mmr-17-01-1469", "version": null, "note": "KEGG and PANTHER functional annotation for most significantly related targets of miR133a-3p.", "structure": {"pmcid": "PMC5780086", "section_index": 21, "section_title": "Targets prediction and functional enrichment", "row_count": 20, "column_count": 7}, "table": {"label": "Table III.", "caption": "KEGG and PANTHER functional annotation for most significantly related targets of miR133a-3p.", "rows": [["KEGG ID", "KEGG term", "Count (%)", "P-value", "Benjamini", "FDR", "Genesa"], ["hsa04020", "Calcium signaling pathway", "21 (0.3)", "2.94E-04", "0.044902", "0.353432", "PTGER3, NOS1, TACR1, CACNA1I, HTR4, OXTR, PTGFR, PRKCB, ADRB1, CAMK4"], ["hsa04080", "Neuroactive ligand-receptor interaction", "25 (0.3)", "0.001306", "0.096932", "1.559243", "AVPR2, ADORA3, TACR1, OPRK1, PTH1R, LPAR3, OXTR, GABBR2, GALR2,ADRA2B"], ["hsa04340", "Hedgehog signaling pathway", "9 (0.1)", "0.005185", "0.236846", "6.058102", "WNT10B, WNT4, WNT7B, HHIP, LRP2, BMP7, BMP8B, ZIC2, WNT2B"], ["hsa04010", "MAPK signaling pathway", "23 (0.3)", "0.009768", "0.318076", "11.13201", "PDGFA, MAP2K3, CACNA1I, FGF23, CACNG4, CACNB3, ACVR1C, TGFB2, CDC25B, PRKCB"], ["hsa04360", "Axon guidance", "13 (0.2)", "0.022042", "0.501133", "23.50711", "EPHA7, SEMA6C, EFNB3, LIMK2, PAK3, LIMK1, EFNA3, NFATC4, EFNA4, CXCL12"], ["hsa05200", "Pathways in cancer", "25 (0.3)", "0.027097", "0.51044", "28.12737", "E2F1, APC2, PDGFA, MMP9, ARNT2, FOXO1, TGFB2, ACVR1C, WNT4, CDKN2B"], ["hsa00071", "Fatty acid metabolism", "6 (0.1)", "0.042643", "0.621365", "40.78121", "ACADSB, ACADS, ALDH1B1, ADH6, ADH1B, ACSL6"], ["hsa05217", "Basal cell carcinoma", "7 (0.1)", "0.048982", "0.624439", "45.32723", "DVL2, WNT10B, WNT4, WNT7B, APC2, HHIP, WNT2B"], ["hsa05410", "Hypertrophic cardiomyopathy (HCM)", "9 (0.1)", "0.052995", "0.610863", "48.03755", "ACE, CACNG4, ITGA10, CACNB3, ITGA3, PRKAA2, TPM2, CACNA1C, TGFB2"], ["hsa00280", "Valine, leucine and isoleucine degradation", "6 (0.1)", "0.060294", "0.620966", "52.65274", "BCAT1, ALDH6A1, ACADSB, ACADS, ALDH1B1, AOX1"], ["hsa04310", "Wnt signaling pathway", "13 (0.2)", "0.06213", "0.597346", "53.75325", "DVL2, WNT10B, WNT4, WNT7B, NKD1, SFRP1, APC2, SFRP4, CAMK2B, NFATC4"], ["hsa00982", "Drug metabolism", "7 (0.1)", "0.078798", "0.655957", "62.7222", "CYP3A4, GSTM2, FMO2, AOX1, ADH6, ADH1B, UGT2B10"], ["P05734", "Synaptic vesicle trafficking", "12 (0.2)", "4.32E-05", "0.004006", "0.047245", "SYP, RAB3A, SYT1, RAB3B, STX1A, RAB3C, SYT2, SYT3, VAMP1, SNAP25"], ["P00004", "Alzheimer disease-presenilin pathway", "19 (0.3)", "0.001606", "0.072016", "1.744225", "DVL2, WNT10B, TRPC3, LDLR, MMP9, CDH3, MMP14, CTNNA3, WNT2B, PCSK"], ["P00003", "Alzheimer disease-amyloid secretase pathway", "11 (0.1)", "0.015543", "0.384681", "15.75932", "MAPK12, CHRM3, MAPK13, BACE2, CACNB3, KLC2, CHRFAM7A, CACNA1C, PCSK5, PRKCB"], ["P00012", "Cadherin signaling pathway", "18 (0.2)", "0.021774", "0.4006", "21.41572", "WNT10B, PCDHGC5, PCDH9, CDH3, PCDH17, PCDHGA4, PCDHGB2, PCDHGA2, CTNNA3"], ["P00040", "Metabotropic glutamate receptor group II pathway", "8 (0.1)", "0.046646", "0.588732", "40.72335", "BDNF, GNAO1, CACNA1E, CACNB3, VAMP1, SNAP25, CACNA1A"], ["P00050", "Plasminogen activating cascade", "5 (0.1)", "0.048863", "0.539986", "42.2145", "MMP9, SERPINE1, MMP3, PLG"], ["P00037", "Ionotropic glutamate receptor pathway", "8 (0.1)", "0.065277", "0.592151", "52.24159", "CACNG4, CACNA1E, CAMK2B, VAMP1, CAMK2A, SNAP25, CACNA1A"]], "row_count": 20, "column_count": 7, "numeric_cells": 108, "header_rows": 1, "locator": "section[21]/table-wrap[2]#tIII-mmr-17-01-1469"}}, {"id": "asset:table:pmid:29138825:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7b77802f4a6893e48872cf21298a99f2b2da89b5e9b0a9c6f47333f06f864d03", "bytes": 1828, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[23]/table-wrap[1]#tIV-mmr-17-01-1469", "version": null, "note": "Expressions of 21 genes based on The Cancer Genome Atlas dataset (374 HCC tissues and 50 normal liver tissues).", "structure": {"pmcid": "PMC5780086", "section_index": 23, "section_title": "Validation of some potential target gene expression based on TCGA dataset", "row_count": 22, "column_count": 6}, "table": {"label": "Table IV.", "caption": "Expressions of 21 genes based on The Cancer Genome Atlas dataset (374 HCC tissues and 50 normal liver tissues).", "rows": [["Gene name", "HCC tissue (Mean ± SD)", "Normal liver tissue (Mean ± SD)", "t", "P-value", "FC"], ["CACNA1E", "3.86±2.16", "1.81±1.33", "−5.97", "3.64×10−6a", "2.05"], ["HTR4", "3.52±1.89", "2.13±1.14", "−5.82", "5.36×10−7a", "1.4"], ["CACNA1C", "6.5±1.65", "5.38±1.03", "−6.62", "2.81×10−9a", "1.12"], ["CHRM3", "6.3±2.12", "5.23±1.4", "−4.7", "1.02×10−5a", "1.07"], ["OXTR", "4.91±1.79", "3.86±1.66", "−3.83", "1.47×10−4a", "1.04"], ["CACNA1I", "3.51±2.18", "2.51±1.24", "−4.03", "1.60×10−4a", "1.00"], ["CACNA1A", "3.73±1.3", "2.85±0.82", "−6.44", "7.71×10−9a", "0.88"], ["CHRFAM7A", "2.25±1.35", "1.38±0.48", "−4.22", "7.54×10−4a", "0.86"], ["PTGER3", "4.88±1.73", "4.03±1.42", "−3.23", "1.35×10−3a", "0.84"], ["TACR1", "3.21±1.7", "2.38±0.91", "−4.65", "1.46×10−5a", "0.84"], ["CAMK2A", "3.6±2.19", "2.82±1.03", "−3.94", "1.34×10−4a", "0.78"], ["ADRA1D", "3.61±2.26", "3.27±1.74", "−0.72", "4.69×10−1", "0.34"], ["PTGFR", "5.92±3.04", "5.6±1.21", "−1.37", "1.74×10−1", "0.32"], ["NOS1", "2.64±1.84", "2.97±0.98", "1.66", "9.98×10−2", "−0.33"], ["PRKCB", "6.67±1.65", "7.78±1.43", "4.56", "6.62×10−6a", "−1.12"], ["ADRA1A", "5.78±2.62", "6.95±4.59", "1.76", "8.35×10−2", "−1.17"], ["ADRB1", "3.71±1.76", "5.03±1.49", "5.71", "2.37×10−7a", "−1.33"], ["TBXA2R", "6.87±1.09", "8.32±1.17", "8.28", "1.46×10−11a", "−1.45"], ["CAMK4", "5.25±1.44", "7±1.09", "10.17", "1.09×10−15a", "−1.74"], ["ADRA1B", "6.55±1.86", "8.47±0.74", "13.47", "8.19×10−28a", "−1.92"], ["CAMK2B", "5.32±2.63", "8.55±0.89", "17.13", "3.33×10−41a", "−3.23"]], "row_count": 22, "column_count": 6, "numeric_cells": 105, "header_rows": 1, "locator": "section[23]/table-wrap[1]#tIV-mmr-17-01-1469"}}], "gaps": ["asset:data:geo:GSE12717 not downloaded", "asset:data:geo:GSE12717 licence not read", "asset:data:geo:GSE21362 not downloaded", "asset:data:geo:GSE21362 licence not read", "asset:data:geo:GSE22058 not downloaded", "asset:data:geo:GSE22058 licence not read", "asset:data:geo:GSE40744 not downloaded", "asset:data:geo:GSE40744 licence not read", "asset:data:geo:GSE41874 not downloaded", "asset:data:geo:GSE41874 licence not read", "asset:data:geo:GSE54751 not downloaded", "asset:data:geo:GSE54751 licence not read", "asset:data:geo:GSE57555 not downloaded", "asset:data:geo:GSE57555 licence not read", "asset:data:geo:GSE69580 not downloaded", "asset:data:geo:GSE69580 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Student's t-test was applied to verify the difference between two corresponding groups of various clinical features."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "student_t", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "student_t", "expected_value": 0.001, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.student_t"]}, "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": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE57555", "GSE69580", "GSE54751", "GSE41874", "GSE40744", "GSE21362", "GSE22058", "GSE12717"], "resolved_accessions": ["GSE57555", "GSE69580", "GSE54751", "GSE41874", "GSE40744", "GSE21362", "GSE22058", "GSE12717"], "statements": ["The authors first searched GEO datasets to assess the expression of miR-133a-3p between HCC and non-cancer tissues. miR-133a-3p levels in eight datasets GSE57555 (Japan), GSE69580 (Taiwan), GSE54751 (USA), GSE41874 (Japan), GSE40744 (USA), GSE21362 (Japan), GSE22058 (USA) and GSE12717 (USA) which included 217 HCC and 219 normal tissues are presented in Fig. 3."], "basis": "The paper names GSE57555, GSE69580, GSE54751, GSE41874, GSE40744, GSE21362, GSE22058, GSE12717 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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