Integrated bioinformatics analysis and experimental validation to understand tryptophan metabolism-related genes in hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39132147", "kind": "science-record", "revision": 2, "content_hash": "sha256:0efa48c89051ac96a1c912278c4909aa66f8d2081db2619eb075e59bd4853486", "created_at": "2026-11-01T20:29:14Z", "updated_at": "2026-11-01T21:33:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated bioinformatics analysis and experimental validation to understand tryptophan metabolism-related genes in hepatocellular carcinoma.", "doi": "10.7150/jca.91306", "pmid": "39132147", "authors": ["Hao Chen", "Wu Sun", "Mengxiao Xie", "Zhenhan Li", "Bofeng Chen", "Tao Zhang", "Le Lv", "Lizhen Wang", "Linming Lu", "Qianli Tang", "Liangping Luo"], "journal": "Journal of Cancer", "year": 2024, "abstract": "Background: Tryptophan (Trp) metabolism is closely related to tumor immunity, and its disorder can cause an immunosuppressive microenvironment, promoting the occurrence and development of hepatocellular carcinoma (HCC). The aim of this study is to explore and validate the independent prognostic genes in patients suffered from HCC. Methods: The transcriptome data of GSE87630 from GEO database were downloaded to analyze differentially expressed genes (DECs) which were intersected with the gene sets of Trp metabolism from MsigDB database. Univariate/multivariate COX regression was performed to identify the genes with independent prognostic significance. TCGA, GTEx, UALCAN, and GEPIA2 databases were applied to analyze DEGs for prognosis. RNA seq data of HCC from TCGA database were collected for Lasso regression analysis. The ssGSEA algorithm was used to perform the analysis of TCGA data. The effects of the candidate differential gene on HCC cells proliferation and migration were evaluated using EdU immunofluorescence and transwell assays. Results: Trp metabolism-related DECs for HCCs were obtained, including MAOB, CYP1A2, KYNU, CYP2E1, ALDH2, CYP2C18, TDO2, AOX1, CYP3A4 and INMT. Moreover, multivariate COX regression results showed that ALDH2 can serve as an independent prognostic molecule and its transcriptional and translational levels were significantly reduced in the tumor tissues. The low expression of ALDH2 was associated with poor prognosis. Overexpression of ALDH2 dramatically reduced the HCC cells proliferation and migration. Conclusion: ALDH2 is associated with Trp metabolism and its downregulation in HCC has a potential value on prognosis. Overexpression of ALDH2 can reduce the proliferation and migration of HCC cells.", "claims": [{"id": "claim-method", "statement": "The single factor/multi factor COX regression analysis were conducted on the TCGA data after previous conversion.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39132147", "locator": "sections[7] \"Univariate and Multivariate analysis of COX regression\" paragraph 2", "quote": "The single factor/multi factor COX regression analysis were conducted on the TCGA data after previous conversion."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used to support the findings of this study are available from GEO database, TCGA database and UCSC Xena. Additional information may be obtained upon reasonable request from the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39132147", "locator": "sections[29] \"ack\" paragraph 1", "quote": "The datasets used to support the findings of this study are available from GEO database, TCGA database and UCSC Xena. Additional information may be obtained upon reasonable request from the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ALDH2 was identified by multivariate COX regression as an independent prognostic molecule, and low ALDH2 expression was associated with poorer prognosis; the reported survival result was HR=0.46, P<0.001.", "kind": "quantitative", "target": {"value": 0.46, "unit": "hazard ratio", "tolerance": null, "source": "The results showed that patients in the group with lower ALDH2 expression had poorer prognosis outcomes (HR=0.46, P<0.001)."}, "evidence": [{"asset": "source:pmid:39132147", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Moreover, multivariate COX regression results showed that ALDH2 can serve as an independent prognostic molecule and its transcriptional and translational levels were significantly reduced in the tumor tissues."}, {"asset": "source:pmid:39132147", "locator": "sections[22] \"Identification of differentially expressed ALDH2 and its clinical value\" paragraph 2", "quote": "The results showed that patients in the group with lower ALDH2 expression had poorer prognosis outcomes (HR=0.46, P<0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ALDH2 was identified by multivariate COX regression as an independent prognostic molecule, and low ALDH2 expression was associated with poorer prognosis; the reported survival result was HR=0.46, 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:39132147"], "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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Methods: The transcriptome data of GSE87630 from GEO database were down", "SC XENA (https://xenabrowser.net/datapages/) RNAseq data in TPM format of TCGA and GTEx were pro", "red between the samples after converting the RNAseq data in TPM format into log2. At the same ti"], "order_basis": "paper_text_order:444", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ation and migration were evaluated using EdU immunofluorescence and transwell assays. Results: Trp metabolis", "llular carcinoma and the normal tissues. The immunohistochemical images of HCC and normal tissues were obtain"], "order_basis": "paper_text_order:1107", "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": ["iCell Bioscience Inc (Shanghai, China). The cell lines were cultured in DMEM supplemented with 10% FBS, 100 U/ml", "e Inc (Shanghai, China). The cell lines were cultured in DMEM supplemented with 10% FBS, 100 U/ml pen", "GEPIA2. Experimental validation Cell culture HepG2 and HCC-LM3 HCC cell lines were obtained fro"], "order_basis": "paper_text_order:3206", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The single factor/multi factor COX regression analysis were conducted on the TCGA data after previous conversion."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}