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pmid:31190871
Identification and validation of an individualized autophagy-clinical prognostic index in bladder cancer patients.
Shi-Shuo Wang · Gang Chen · Sheng-Hua Li · Jin-Shu Pang · Kai-Teng Cai · Hai-Biao Yan · Zhi-Guang Huang · Rong-Quan He
OncoTargets and therapy · 2019 doi:10.2147/OTT.S197676
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Complete file
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An abnormal autophagic level is implicated in the pathogenesis of multiple diseases, including cancers. The aim of this study is to explore the prognostic value of autophagy in bladder cancer (BC), which is a major cause of cancer-related death globally. Patients and methods: First, 27 differentially expressed autophagy-related genes (ARGs) were identified in BC patients based on The Cancer Genome Atlas (TCGA) database. Functional enrichment analyses hinted that autophagy may act in a tumor-suppressive role in the initiation of BC. Then, the Cox proportional hazard regression model were employed to identify three key prognostic ARGs (JUN, MYC, and ITGA3), which were related with overall survival (OS) significantly in BC. The three genes represented important clinical significance and prognostic value in BC. Then a prognostic index (PI) was constructed. Results: The PI was constructed based on the three genes, and significantly stratified BC patients into high- and low-risk groups in terms of OS (HR=1.610, 95% CI=1.200-2.160, P=0.002). PI remained as an independent prognostic factor in multivariate analyses (HR=2.355, 95% CI=1.483-3.739, P<0.001). When integrated with clinical characteristics of age and stage, an autophagy-clinical prognostic index (ACPI) was finally validated, which had improved performance in predicting OS of BC patients (HR=2.669, 95% CI=1.986-3.587, P<0.001). The ACPI was confirmed in datasets of GSE13507 (HR=7.389, 95% CI=3.645-14.980, P<0.001) and GSE31684 (HR=1.665, 95% CI=0.872-3.179, P=0.122). Conclusion: This study provides a potential prognostic signature for predicting prognosis of BC patients and molecular insights of autophagy in BC.", "claims": [{"id": "claim-method", "statement": "The Multivariate Cox proportional hazards regression model was used to construct the PI and ACPI model based on the factor correlated with survival.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31190871", "locator": "sections[6] \"Statistical analysis\" paragraph 2", "quote": "The Multivariate Cox proportional hazards regression model was used to construct the PI and ACPI model based on the factor correlated with survival."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The RNA-seq data and clinical information of BC analyzed in this study can be downloaded from The Cancer Genome Atlas (TCGA). 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"downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE24152", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24152", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE24152", "version": null, "note": "The RNA-seq data and clinical information of BC analyzed in this study can be downloaded from The Cancer Genome Atlas (TCGA). The microarray data of GSE13507, GSE31684, GSE76211, GSE2109, GSE7476, GSE30522, GSE31189, GSE37815, GSE52519, GSE65635, GSE37817, GSE100926, GSE24152, GSE19915 (GPL3883 and GPL5186), and GSE40355 can be acquired from the Gene Expression Omnibus (GEO) database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The RNA-seq data and clinical information of BC analyzed in this study can be downloaded from The Cancer Genome Atlas (TCGA). 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The microarray data of GSE13507, GSE31684, GSE76211, GSE2109, GSE7476, GSE30522, GSE31189, GSE37815, GSE52519, GSE65635, GSE37817, GSE100926, GSE24152, GSE19915 (GPL3883 and GPL5186), and GSE40355 can be acquired from the Gene Expression Omnibus (GEO) database.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM180991", "GSM180992", "GSM180993", "GSM180994", "GSM180995", "GSM180996", "GSM180997", "GSM180998", "GSM180999", "GSM181000", "GSM181001", "GSM181002"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Analysis of clinical bladder cancer classification according to microarray expression profiles", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE76211", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76211", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76211", "version": null, "note": "The RNA-seq data and clinical information of BC analyzed in this study can be downloaded from The Cancer Genome Atlas (TCGA). The microarray data of GSE13507, GSE31684, GSE76211, GSE2109, GSE7476, GSE30522, GSE31189, GSE37815, GSE52519, GSE65635, GSE37817, GSE100926, GSE24152, GSE19915 (GPL3883 and GPL5186), and GSE40355 can be acquired from the Gene Expression Omnibus (GEO) database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The RNA-seq data and clinical information of BC analyzed in this study can be downloaded from The Cancer Genome Atlas (TCGA). The microarray data of GSE13507, GSE31684, GSE76211, GSE2109, GSE7476, GSE30522, GSE31189, GSE37815, GSE52519, GSE65635, GSE37817, GSE100926, GSE24152, GSE19915 (GPL3883 and GPL5186), and GSE40355 can be acquired from the Gene Expression Omnibus (GEO) database.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1976573", "GSM1976574", "GSM1976575", "GSM1976577", "GSM1976579", "GSM1976580"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "17586", "taxon": "Homo sapiens", "title": "mRNA Expression data from bladder cancer and normal bladder tissue", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:31190871:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e960820ce9a6f3142fbdb0dec88b5b81ffd43104040007f915439492b3b6088b", "bytes": 4950, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#T0001", "version": null, "note": "GO and KEGG analysis of differentially expressed autophagy-related genes", "structure": {"pmcid": "PMC6526186", "section_index": 9, "section_title": "Functional annotation of the differentially expressed ARGs", "row_count": 41, "column_count": 5}, "table": {"label": "Table 1", "caption": "GO and KEGG analysis of differentially expressed autophagy-related genes", "rows": [["Category", "ID", "Term", "P-value", "Genes"], ["Biological Process", "GO:0042493", "Response to drug", "4.44E−06", "FOS, CDKN1A, JUN, BCL2, ITGA3, MYC, TP73"], ["Biological Process", "GO:0010332", "Response to gamma radiation", "1.27E−05", "CCL2, BCL2, MYC, TP73"], ["Biological Process", "GO:0006915", "Apoptotic process", "1.36E−05", "DLC1, EVA1A, CDKN2A, CXCR4, BCL2, BIRC5, PPP1R15A, TP73"], ["Biological Process", "GO:0007346", "Regulation of mitotic cell cycle", "2.78E−05", "CDKN1A, BIRC5, MYC, TP73"], ["Biological Process", "GO:0043524", "Negative regulation of neuron apoptotic process", "4.06E−05", "CCL2, JUN, BCL2, BIRC5, TP73"], ["Biological Process", "GO:0007050", "Cell cycle arrest", "5.25E−05", "CDKN1A, CDKN2A, PPP1R15A, MYC, TP73"], ["Biological Process", "GO:0006974", "Cellular response to DNA damage stimulus", "2.36E−04", "CDKN1A, BCL2, PPP1R15A, MYC, TP73"], ["Biological Process", "GO:0001836", "Release of cytochrome c from mitochondria", "5.28E−04", "BID, JUN, BCL2"], ["Biological Process", "GO:0045893", "Positive regulation of transcription, DNA-templated", "8.50E−04", "FOS, CDKN2A, JUN, MYC, TP53INP2, TP73"], ["Biological Process", "GO:1900740", "Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway", "9.02E−04", "BID, BCL2, TP73"], ["Cellular Component", "GO:0005829", "Cytosol", "3.94E−06", "BID, DLC1, NAMPT, GABARAPL1, BIRC5, TP73, FOS, CDKN1A, EIF4EBP1, CDKN2A, JUN, BCL2, BAG3, MYC, PPP1R15A, TP53INP2"], ["Cellular Component", "GO:0043234", "Protein complex", "0.002235", "EIF4EBP1, CDKN1A, CDKN2A, MYC, ITPR1"], ["Cellular Component", "GO:0005739", "Mitochondrion", "0.007959", "BID, GABARAPL1, CDKN2A, BCL2, PPP1R15A, MYC, TP73"], ["Cellular Component", "GO:0005654", "Nucleoplasm", "0.008942", "NAMPT, FOS, EIF4EBP1, CDKN1A, CDKN2A, JUN, HSPB8, BIRC5, MYC, TP73"], ["Cellular Component", "GO:0005741", "Mitochondrial outer membrane", "0.017612", "BID, BCL2, PPP1R15A"], ["Cellular Component", "GO:0030054", "Cell junction", "0.024203", "NAMPT, CXCR4, ITGB4, TP73"], ["Cellular Component", "GO:0005783", "Endoplasmic reticulum", "0.025005", "FOS, GABARAPL1, BCL2, PPP1R15A, ITPR1"], ["Cellular Component", "GO:0005667", "Transcription factor complex", "0.028532", "FOS, JUN, TP73"], ["Cellular Component", "GO:0005794", "Golgi apparatus", "0.028578", "GABARAPL1, HSPB8, RGS19, PPP1R15A"], ["Cellular Component", "GO:0008305", "Integrin complex", "0.036412", "ITGB4, ITGA3"], ["Cellular Component", "GO:0005515", "Protein binding", "3.97E−05", "BID, DLC1, NAMPT, GABARAPL1, ITGB4, RGS19, BIRC5, ITGA3, CX3CL1, TP73, ITPR1, FOS, CDKN1A, EIF4EBP1, CDKN2A, CXCR4, JUN, HSPB8, BCL2, BAG3, MYC, PPP1R15A, TP53INP2"], ["Molecular Function", "GO:0008134", "Transcription factor binding", "4.25E−05", "FOS, CDKN2A, JUN, BCL2, MYC, TP73"], ["Molecular Function", "GO:0031625", "Ubiquitin protein ligase binding", "6.65E−04", "BID, GABARAPL1, CDKN1A, CXCR4, BCL2"], ["Molecular Function", "GO:0046982", "Protein heterodimerization activity", "0.003898", "FOS, JUN, BCL2, BIRC5, ITGA3"], ["Molecular Function", "GO:0001077", "Transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding", "0.004395", "FOS, JUN, MYC, TP73"], ["Molecular Function", "GO:0043565", "Sequence-specific DNA binding", "0.005716", "FOS, JUN, BCL2, MYC, TP73"], ["Molecular Function", "GO:0000978", "RNA polymerase II core promoter proximal region sequence-specific DNA binding", "0.013453", "FOS, JUN, MYC, TP73"], ["Molecular Function", "GO:0004861", "Cyclin-dependent protein serine/threonine kinase inhibitor activity", "0.015533", "CDKN1A, CDKN2A"], ["Molecular Function", "GO:0019901", "Protein kinase binding", "0.015684", "CDKN2A, RGS19, PPP1R15A, TP73"], ["Molecular Function", "GO:0042802", "Identical protein binding", "0.020127", "JUN, HSPB8, BCL2, BIRC5, TP73"], ["KEGG PATHWAY", "hsa05200", "Pathways in cancer", "3.16E−07", "BID, FOS, CDKN1A, CDKN2A, CXCR4, JUN, BCL2, BIRC5, ITGA3, MYC"], ["KEGG PATHWAY", "hsa05210", "Colorectal cancer", "2.06E−05", "FOS, JUN, BCL2, BIRC5, MYC"], ["KEGG PATHWAY", "hsa05161", "Hepatitis B", "3.48E−05", "FOS, CDKN1A, JUN, BCL2, BIRC5, MYC"], ["KEGG PATHWAY", "hsa04012", "ErbB signaling pathway", "7.87E−05", "EIF4EBP1, CDKN1A, JUN, NRG2, MYC"], ["KEGG PATHWAY", "hsa04115", "p53 signaling pathway", "7.56E−04", "BID, CDKN1A, CDKN2A, TP73"], ["KEGG PATHWAY", "hsa04151", "PI3K-Akt signaling pathway", "0.001961", "EIF4EBP1, CDKN1A, BCL2, ITGB4, ITGA3, MYC"], ["KEGG PATHWAY", "hsa04668", "TNF signaling pathway", "0.002843", "FOS, CCL2, JUN, CX3CL1"], ["KEGG PATHWAY", "hsa05166", "HTLV-I infection", "0.004594", "FOS, CDKN1A, CDKN2A, JUN, MYC"], ["KEGG PATHWAY", "hsa05219", "Bladder cancer", "0.00551", "CDKN1A, CDKN2A, MYC"], ["KEGG PATHWAY", "hsa04921", "Oxytocin signaling pathway", "0.008685", "FOS, CDKN1A, JUN, ITPR1"]], "row_count": 41, "column_count": 5, "numeric_cells": 106, "header_rows": 1, "locator": "section[9]/table-wrap[1]#T0001"}}, {"id": "asset:table:pmid:31190871:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:85290b1004f06323d417f99574c28833ca5b20ce382eb206080b666856c474f4", "bytes": 4540, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#T0002", "version": null, "note": "Expression and Cox regression analysis data of the prognosis-related ARGs in bladder cancer by TCGA", "structure": {"pmcid": "PMC6526186", "section_index": 10, "section_title": "Identification of prognostic ARGs", "row_count": 56, "column_count": 10}, "table": {"label": "Table 2", "caption": "Expression and Cox regression analysis data of the prognosis-related ARGs in bladder cancer by TCGA", "rows": [["Gene", "Expression", "Univariate Cox", "Multivariate Cox"], ["mean±SD", "P-value", "HR", "z", "P-value", "HR", "z", "P-value"], ["JUN", "Tumor", "13.002773±1.164031", "<0.0001", "1.198762", "2.651598", "0.008011", "1.1786", "2.38", "0.017"], ["", "Non-tumor", "15.027896±1.185059", "", "", "", "", "", "", ""], ["MYC", "Tumor", "11.541411±1.554496", "<0.0001", "1.14059", "2.606545", "0.009146", "1.1682", "2.97", "0.003"], ["", "Non-tumor", "13.287664±1.265550", "", "", "", "", "", "", ""], ["ITGA3", "Tumor", "13.822128±1.515658", "<0.0001", "0.907077", "−2.0139", "0.04402", "−0.1505", "−2.97", "0.003"], ["", "Non-tumor", "12.975430±1.091134", "", "", "", "", "", "", ""], ["NAMPT", "Tumor", "12.330813±1.009040", "<0.0001", "1.172207", "2.001379", "0.045352", "", "", "0.340"], ["", "Non-tumor", "13.308780±1.459465", "", "", "", "", "", "", ""], ["FOS", "Tumor", "13.343147±1.608937", "<0.0001", "1.063323", "1.267733", "0.204893", "", "", ""], ["", "Non-tumor", "16.672991±1.404332", "", "", "", "", "", "", ""], ["HSPB8", "Tumor", "10.106659±2.154647", "<0.0001", "1.068919", "1.911278", "0.055969", "", "", ""], ["", "Non-tumor", "13.749171±1.702493", "", "", "", "", "", "", ""], ["CDKN1A", "Tumor", "13.124746±1.128535", "<0.0001", "1.01594", "0.22579", "0.821364", "", "", ""], ["", "Non-tumor", "14.389922±1.347070", "", "", "", "", "", "", ""], ["ITPR1", "Tumor", "9.5318665±1.169013", "<0.0001", "0.997873", "−0.03415", "0.972754", "", "", ""], ["", "Non-tumor", "11.929274±1.585768", "", "", "", "", "", "", ""], ["TP53INP2", "Tumor", "10.462387±0.976958", "<0.0001", "1.119264", "1.518161", "0.128974", "", "", ""], ["", "Non-tumor", "12.653637±1.109542", "", "", "", "", "", "", ""], ["BIRC5", "Tumor", "11.387251±1.094559", "<0.0001", "1.06901", "0.897696", "0.369347", "", "", ""], ["", "Non-tumor", "7.9468232±2.565110", "", "", "", "", "", "", ""], ["PPP1R15A", "Tumor", "12.441886±0.891543", "<0.0001", "0.940067", "−0.71379", "0.475356", "", "", ""], ["", "Non-tumor", "13.738993±1.001618", "", "", "", "", "", "", ""], ["DLC1", "Tumor", "9.5131164±1.257221", "<0.0001", "1.021996", "0.347978", "0.727857", "", "", ""], ["", "Non-tumor", "11.242183±0.995269", "", "", "", "", "", "", ""], ["BAG3", "Tumor", "11.719572±0.731981", "<0.0001", "1.192655", "1.702932", "0.088581", "", "", ""], ["", "Non-tumor", "12.704785±1.108736", "", "", "", "", "", "", ""], ["GABARAPL1", "Tumor", "11.058632±0.792235", "<0.0001", "1.051224", "0.525272", "0.599394", "", "", ""], ["", "Non-tumor", "12.255963±0.614109", "", "", "", "", "", "", ""], ["BCL2", "Tumor", "8.3027604±1.178505", "<0.0001", "1.051513", "0.768008", "0.442482", "", "", ""], ["", "Non-tumor", "10.256868±0.425816", "", "", "", "", "", "", ""], ["CDKN2A", "Tumor", "8.9951212±3.453185", "<0.0001", "0.990449", "−0.44257", "0.658076", "", "", ""], ["", "Non-tumor", "6.6235955±1.685343", "", "", "", "", "", "", ""], ["CCL2", "Tumor", "9.0438964±1.821760", "<0.0001", "1.053817", "1.273601", "0.202805", "", "", ""], ["", "Non-tumor", "11.704824±2.040782", "", "", "", "", "", "", ""], ["PRKN", "Tumor", "5.2978598±1.521700", "<0.0001", "1.009973", "0.201647", "0.840193", "", "", ""], ["", "Non-tumor", "8.1483213±1.213423", "", "", "", "", "", "", ""], ["BID", "Tumor", "11.340986±0.737984", "<0.0001", "0.839371", "−1.70367", "0.088442", "", "", ""], ["", "Non-tumor", "10.105586±0.651137", "", "", "", "", "", "", ""], ["EVA1A", "Tumor", "6.5437907±2.147278", "<0.0001", "1.057202", "1.528728", "0.126332", "", "", ""], ["", "Non-tumor", "3.8921911±1.267249", "", "", "", "", "", "", ""], ["CXCR4", "Tumor", "10.259886±1.380760", "<0.0001", "1.013263", "0.261675", "0.793572", "", "", ""], ["", "Non-tumor", "11.447608±1.958345", "", "", "", "", "", "", ""], ["NRG2", "Tumor", "4.7761532±2.145474", "<0.0001", "0.985697", "−0.43265", "0.665266", "", "", ""], ["", "Non-tumor", "7.9643803±1.000720", "", "", "", "", "", "", ""], ["TP73", "Tumor", "7.9164301±2.009466", "<0.0001", "0.984879", "−0.3943", "0.69336", "", "", ""], ["", "Non-tumor", "5.9146373±2.363484", "", "", "", "", "", "", ""], ["RGS19", "Tumor", "9.9259644±0.729683", "<0.0001", "1.143028", "1.313883", "0.188886", "", "", ""], ["", "Non-tumor", "8.6949825±0.978522", "", "", "", "", "", "", ""], ["EIF4EBP1", "Tumor", "11.427944±1.081142", "<0.0001", "1.046433", "0.666103", "0.505345", "", "", ""], ["", "Non-tumor", "9.8783883±0.927159", "", "", "", "", "", "", ""], ["CX3CL1", "Tumor", "9.7520038±1.782426", "<0.0001", "1.034169", "0.77976", "0.435532", "", "", ""], ["", "Non-tumor", "12.084799±0.955857", "", "", "", "", "", "", ""], ["ITGB4", "Tumor", "14.253622±1.551662", "<0.0001", "0.936675", "−1.33788", "0.180934", "", "", ""], ["", "Non-tumor", "13.188612±1.541228", "", "", "", "", "", "", ""]], "row_count": 56, "column_count": 10, "numeric_cells": 176, "header_rows": 2, "locator": "section[10]/table-wrap[1]#T0002"}}, {"id": "asset:table:pmid:31190871:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8455598ce6b03c89b05ae2856fd379ace37272ce14d02e4cbd6e5e3718499832", "bytes": 2514, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[2]#T0003", "version": null, "note": "Relationships between three key prognostic genes expression and clinical parameters in bladder cancer by TCGA", "structure": {"pmcid": "PMC6526186", "section_index": 10, "section_title": "Identification of prognostic ARGs", "row_count": 22, "column_count": 12}, "table": {"label": "Table 3", "caption": "Relationships between three key prognostic genes expression and clinical parameters in bladder cancer by TCGA", "rows": [["Parameters", "N", "JUN expression value", "MYC expression value", "ITGA3 expression value"], ["M±SD", "t value", "P-value", "M±SD", "t value", "P-value", "M±SD", "t value", "P-value"], ["Tissues", "Tumor", "414", "13.0028±1.1640", "−7.410", "<0.001", "11.5414±1.5545", "−4.822", "<0.001", "13.8221±1.5157", "2.405", "0.017"], ["Non-tumor", "19", "15.0279±1.1851", "13.2877±1.2655", "12.9754±1.0911"], ["Age", "≥60", "321", "13.0359±1.1327", "1.076", "0.150", "11.6119±1.5304", "1.571", "0.117", "13.7787±1.5272", "−1.665", "0.097"], ["<60", "87", "12.8852±1.2530", "11.3177±1.6171", "14.0830±1.4561"], ["Gender", "Male", "301", "12.9868±1.1674", "−0.495", "0.621", "11.4625±1.5666", "−1.898", "0.058", "13.7850±1.5661", "−1.311", "0.191"], ["Female", "107", "13.0515±1.1410", "11.7930±1.4901", "14.0084±1.3574"], ["Subtype", "Non-papillary", "271", "13.1979±1.0811", "4.903", "<0.001", "11.7343±1.5708", "3.405", "0.001", "13.7762±1.5897", "−1.492", "0.136"], ["Papillary", "132", "12.6091±1.2284", "11.1787±1.4654", "14.0137±1.2921"], ["Tumor status", "With tumor", "151", "13.0248±1.0119", "0.459", "0.647", "11.6697±1.5948", "1.351", "0.177", "13.7276±1.5787", "1.763", "0.079"], ["Tumor free", "201", "12.9720±1.2459", "11.4571±1.4702", "13.9996±1.4314"], ["Histological grade", "High grade", "384", "13.0359±1.1529", "2.143", "0.033", "11.5759±1.5844", "3.002", "0.005", "13.7990±1.5338", "−6.996", "<0.001"], ["Low grade", "21", "12.4819±1.1653", "11.0637±0.6886", "14.8231±0.5669"], ["Pathologic stage", "Ⅲ~Ⅳ", "274", "13.1826±1.0448", "4.206", "<0.001", "11.6576±1.4617", "1.944", "0.053", "13.7353±1.5386", "−2.136", "0.033"], ["I~II", "132", "12.6367±1.3030", "11.3387±1.7148", "14.0770±1.4496"], ["T stage", "T3–T4", "252", "13.1958±1.0249", 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