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pmid:36504808

CXCL8, CXCL9, CXCL10, and CXCL11 as biomarkers of liver injury caused by chronic hepatitis B.

Xin Yu · Ying Chen · Lele Cui · Kaming Yang · Xumeng Wang · Linyuan Lei · Yanping Zhang · Xinyi Kong · Wanwen Lao · Zhenlin Li · Yang Liu · Yuetong Li · Changlong Bi · Chao Wu · Aixia Zhai

Frontiers in microbiology · 2022 doi:10.3389/fmicb.2022.1052917

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
CXCL8, CXCL9, CXCL10, and CXCL11 as biomarkers of liver injury caused by chronic hepatitis B.
doi
10.3389/fmicb.2022.1052917
pmid
36504808
authors array · 15 items
[0]
Xin Yu
[1]
Ying Chen
[2]
Lele Cui
[3]
Kaming Yang
[4]
Xumeng Wang
[5]
Linyuan Lei
[6]
Yanping Zhang
[7]
Xinyi Kong
[8]
Wanwen Lao
[9]
Zhenlin Li
[10]
Yang Liu
[11]
Yuetong Li
[12]
Changlong Bi
[13]
Chao Wu
[14]
Aixia Zhai
journal
Frontiers in microbiology
year
2022
abstract
Background: Chronic hepatitis B (CHB) remains a significant global health problem, leading to recurrent inflammation and liver-damaging diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, although diagnostic markers for CHB are well established, the indicators for predicting liver injury caused by hepatitis B virus (HBV) infection still need to be further explored. Thus, the identification of credible infectious indicators is urgently needed to facilitate timely clinical intervention and avoid the progression of disease malignancy. Methods: The Gene Expression Omnibus (GEO) database GSE83148 data set was used to explore the hub genes for HBV infection. The quantitative real-time polymerase chain reaction (qPCR) was used to identify the impact of HBV infection on the expression of hub gene at the cell level. At the same time, serum samples and clinical information were collected from healthy, HBV-free and CHB patients. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of cell experiments and Pearson correlation analysis was used to clarify hub genes correlation with HBV infection indicators and liver injury-related indicators. Finally, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the differences in the expression of hub gene in liver injury diseases. Results: Chemokine (C-X-C motif) ligand (CXCL)8, CXCL9, CXCL10, and CXCL11 were identified as hub genes in HBV infection. After HBV infection, the expression of the four chemokines was significantly increased and the concentrations secreted into serum were also increased. Moreover, the four chemokines were significantly correlated with HBV infection-related indicators and liver injury-related indicators, which were positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B e antigen (HBeAg), and negatively correlated with AST/ALT ratio and hepatitis B core antibody (HBcAb). In addition, the expression of CXCL9, CXCL10, and CXCL11 in HCC tissues was significantly higher than in normal tissues. Conclusion: Using a combination of bioinformatics, cell experiments, and clinical correlation analysis, this study showed that CXCL8, CXCL9, CXCL10, and CXCL11 can be used as serum biomarkers to forecast liver injury caused by HBV infection.
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Then the differential expression analysis was carried out using an R package named DESeq2 to identify differentially expressed genes (DEGs) between HBV and normal samples and using R package dplyr to process the data derived from the above analysis.
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Then the differential expression analysis was carried out using an R package named DESeq2 to identify differentially expressed genes (DEGs) between HBV and normal samples and using R package dplyr to process the data derived from the above analysis.
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Ultimately, we identified four HBV infection-related hub genes: CXCL8, CXCL9, CXCL10, and CXCL11, which were all upregulated.
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sections[13] "Identification of hub genes related to HBV infection" paragraph 2
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Ultimately, we identified four HBV infection-related hub genes: CXCL8, CXCL9, CXCL10, and CXCL11, which were all upregulated.
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itative real-time polymerase chain reaction (qPCR) was used to identify the impact of HBV infe
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ents. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of cell expe
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from healthy, HBV-free and CHB patients. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of ce
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1987). HepG2 cells and HepG2.215 cells were cultured in DMEM medium, supplemented with 10% FBS and 1
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assay:5
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36504808", "kind": "science-record", "revision": 4, "content_hash": "sha256:ddd497783e26fa711fbb7088671840473df56e6ca69f0c97a7a4ebc97bee07d4", "created_at": "2026-11-01T19:01:00Z", "updated_at": "2026-11-01T22:50:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CXCL8, CXCL9, CXCL10, and CXCL11 as biomarkers of liver injury caused by chronic hepatitis B.", "doi": "10.3389/fmicb.2022.1052917", "pmid": "36504808", "authors": ["Xin Yu", "Ying Chen", "Lele Cui", "Kaming Yang", "Xumeng Wang", "Linyuan Lei", "Yanping Zhang", "Xinyi Kong", "Wanwen Lao", "Zhenlin Li", "Yang Liu", "Yuetong Li", "Changlong Bi", "Chao Wu", "Aixia Zhai"], "journal": "Frontiers in microbiology", "year": 2022, "abstract": "Background: Chronic hepatitis B (CHB) remains a significant global health problem, leading to recurrent inflammation and liver-damaging diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, although diagnostic markers for CHB are well established, the indicators for predicting liver injury caused by hepatitis B virus (HBV) infection still need to be further explored. Thus, the identification of credible infectious indicators is urgently needed to facilitate timely clinical intervention and avoid the progression of disease malignancy.\nMethods: The Gene Expression Omnibus (GEO) database GSE83148 data set was used to explore the hub genes for HBV infection. The quantitative real-time polymerase chain reaction (qPCR) was used to identify the impact of HBV infection on the expression of hub gene at the cell level. At the same time, serum samples and clinical information were collected from healthy, HBV-free and CHB patients. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of cell experiments and Pearson correlation analysis was used to clarify hub genes correlation with HBV infection indicators and liver injury-related indicators. Finally, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the differences in the expression of hub gene in liver injury diseases.\nResults: Chemokine (C-X-C motif) ligand (CXCL)8, CXCL9, CXCL10, and CXCL11 were identified as hub genes in HBV infection. After HBV infection, the expression of the four chemokines was significantly increased and the concentrations secreted into serum were also increased. Moreover, the four chemokines were significantly correlated with HBV infection-related indicators and liver injury-related indicators, which were positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B e antigen (HBeAg), and negatively correlated with AST/ALT ratio and hepatitis B core antibody (HBcAb). In addition, the expression of CXCL9, CXCL10, and CXCL11 in HCC tissues was significantly higher than in normal tissues.\nConclusion: Using a combination of bioinformatics, cell experiments, and clinical correlation analysis, this study showed that CXCL8, CXCL9, CXCL10, and CXCL11 can be used as serum biomarkers to forecast liver injury caused by HBV infection.", "claims": [{"id": "claim-method", "statement": "Then the differential expression analysis was carried out using an R package named DESeq2 to identify differentially expressed genes (DEGs) between HBV and normal samples and using R package dplyr to process the data derived from the above analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36504808", "locator": "sections[5] \"Data processing and differential expression analysis\" paragraph 2", "quote": "Then the differential expression analysis was carried out using an R package named DESeq2 to identify differentially expressed genes (DEGs) between HBV and normal samples and using R package dplyr to process the data derived from the above analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36504808", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Ultimately, we identified four HBV infection-related hub genes: CXCL8, CXCL9, CXCL10, and CXCL11, which were all upregulated.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36504808", "locator": "sections[13] \"Identification of hub genes related to HBV infection\" paragraph 2", "quote": "Ultimately, we identified four HBV infection-related hub genes: CXCL8, CXCL9, CXCL10, and CXCL11, which were all upregulated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Ultimately, we identified four HBV infection-related hub genes: CXCL8, CXCL9, CXCL10, and CXCL11, which were all upregulated.", "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:36504808"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE83148"], "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:GSE83148"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36504808", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmicb.2022.1052917", "sha256": "sha256:089ab69f0627c64cebbe5197579180404726908a7abfc6bbbe498237bb5c714a", "bytes": 34396, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmicb.2022.1052917", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9730243", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE83148", "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=GSE83148", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE83148", "version": null, "note": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2195416", "GSM2195417", "GSM2195418", "GSM2195419", "GSM2195420", "GSM2195421", "GSM2195422", "GSM2195423", "GSM2195424", "GSM2195425", "GSM2195426", "GSM2195427", "GSM2195428", "GSM2195429", "GSM2195430", "GSM2195431", "GSM2195432", "GSM2195433", "GSM2195434", "GSM2195435", "GSM2195436", "GSM2195437", "GSM2195438", "GSM2195439", "GSM2195440", "GSM2195441", "GSM2195442", "GSM2195443", "GSM2195444", "GSM2195445", "GSM2195446", "GSM2195447", "GSM2195448", "GSM2195449", "GSM2195450", "GSM2195451", "GSM2195452", "GSM2195453", "GSM2195454", "GSM2195455", "GSM2195456", "GSM2195457", "GSM2195458", "GSM2195459", "GSM2195460", "GSM2195461", "GSM2195462", "GSM2195463", "GSM2195464", "GSM2195465", "GSM2195466", "GSM2195467", "GSM2195468", "GSM2195469", "GSM2195470", "GSM2195471", "GSM2195472", "GSM2195473", "GSM2195474", "GSM2195475", "GSM2195476", "GSM2195477", "GSM2195478", "GSM2195479", "GSM2195480", "GSM2195481", "GSM2195482", "GSM2195483", "GSM2195484", "GSM2195485", "GSM2195486", "GSM2195487", "GSM2195488", "GSM2195489", "GSM2195490", "GSM2195491", "GSM2195492", "GSM2195493", "GSM2195494", "GSM2195495", "GSM2195496", "GSM2195497", "GSM2195498", "GSM2195499", "GSM2195500", "GSM2195501", "GSM2195502", "GSM2195503", "GSM2195504", "GSM2195505", "GSM2195506", "GSM2195507", "GSM2195508", "GSM2195509", "GSM2195510", "GSM2195511", "GSM2195512", "GSM2195513", "GSM2195514", "GSM2195515", "GSM2195516", "GSM2195517", "GSM2195518", "GSM2195519", "GSM2195520", "GSM2195521", "GSM2195522", "GSM2195523", "GSM2195524", "GSM2195525", "GSM2195526", "GSM2195527", "GSM2195528", "GSM2195529", "GSM2195530", "GSM2195531", "GSM2195532", "GSM2195533", "GSM2195534", "GSM2195535", "GSM2195536", "GSM2195537", "GSM2291960", "GSM2291961", "GSM2291962", "GSM2291963", "GSM2291964", "GSM2291965"], "sample_count": 128, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data of HBV infected liver tissue", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE83148 not downloaded", "asset:data:geo:GSE83148 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "deseq2", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Then the differential expression analysis was carried out using an R package named DESeq2 to identify differentially expressed genes (DEGs) between HBV and normal samples and using R package dplyr to process the data derived from the above analysis."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Analysis of variance"}}, {"id": "method-3", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pearson correlation"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE83148"], "resolved_accessions": ["GSE83148"], "statements": ["The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE83148 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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HBsAg was detected by Roche cobas e601 aut", "tware (GraphPad Software, La Jolla, CA). The qPCR validation of all samples was tested by a pa"], "order_basis": "paper_text_order:797", "id": "assay:1"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ents. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of cell expe", "from healthy, HBV-free and CHB patients. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of ce", "emokines in serum samples and HBV infection, ELISA experiments were conducted. We tested the co", "and the HBV-infected group were detected by ELISA. The detection limit of CXCL8, CXCL9, CXCL10"], "order_basis": "paper_text_order:1018", "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": 0.99, "evidence": ["1987). HepG2 cells and HepG2.215 cells were cultured in DMEM medium, supplemented with 10% FBS and 1", "base. Cell culture A liver cancer cell line (HepG2) derived from a 15-year-old Caucasian boy is", "often used to study liver-related diseases. HepG2.215 cells are derived from HepG2 cells and a", "d diseases. HepG2.215 cells are derived from HepG2 cells and are transfected with four 5′-3′ ta"], "order_basis": "paper_text_order:5467", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["5 cells are derived from HepG2 cells and are transfected with four 5′-3′ tandem copies of the HBV gen"], "order_basis": "paper_text_order:5615", "id": "assay:4"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Then the differential expression analysis was carried out using an R package named DESeq2 to identify differentially expressed genes (DEGs) between HBV and normal samples and using R package dplyr to process the data derived from the above analysis."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}