Survival-related indicators ALOX12B and SPRR1A are associated with DNA damage repair and tumor microenvironment status in HPV 16-negative head and neck squamous cell carcinoma patients.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35768785", "kind": "science-record", "revision": 4, "content_hash": "sha256:d72d183373ae55bf47f23b65f5853a3f852d108437b18c3ce198451c55cedc69", "created_at": "2026-11-01T18:14:48Z", "updated_at": "2026-11-01T22:06:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Survival-related indicators ALOX12B and SPRR1A are associated with DNA damage repair and tumor microenvironment status in HPV 16-negative head and neck squamous cell carcinoma patients.", "doi": "10.1186/s12885-022-09722-x", "pmid": "35768785", "authors": ["Jing Li", "Ling-Long Tang", "Jun Ma"], "journal": "BMC cancer", "year": 2022, "abstract": "OBJECTIVES: To investigate prognostic-related gene signature based on DNA damage repair and tumor microenvironment statue in human papillomavirus 16 negative (HPV16-) head and neck squamous cell carcinoma (HNSCC).\nMETHODS: For the RNA-sequence matrix in HPV16- HNSCC in the Cancer Genome Atlas (TCGA) cohort, the DNA damage response (DDR) and tumor microenvironment (TM) status of each patient sample was estimated by using the ssGSEA algorithm. Through bioinformatics analysis in DDR_high/TM_high (n = 311) and DDR_high/TM_low (n = 53) groups, a survival-related gene signature was selected in the TCGA cohort. Two independent external validation cohorts (GSE65858 (n = 210) and GSE41613 (n = 97)) with HPV16- HNSCC patients validated the gene signature. Correlations among the clinical-related hub differentially expressed genes (DEGs) and infiltrated immunocytes were explored with the TIMER2.0 server. Drug screening based on hub DEGs was performed using the CellMiner and GSCALite databases. The loss-of-function studies were used to evaluate the effect of screened survival-related gene on the motility of HPV- HNSCC cells in vitro.\nRESULTS: A high DDR level (P = 0.025) and low TM score (P = 0.012) were independent risk factors for HPV16- HNSCC. Downregulated expression of ALOX12B or SPRR1A was associated with poor survival rate and advanced cancer stages. The pathway enrichment analysis showed the DDR_high/TM_low samples were enriched in glycosphingolipid biosynthesis-lacto and neolacto series, glutathione metabolism, platinum drug resistance, and ferroptosis pathways, while the DDR_high/TM_low samples were enriched in Th17 cell differentiation, Neutrophil extracellular trap formation, PD - L1 expression and PD - 1 checkpoint pathway in cancer. Notably, the expression of ALOX12B and SPRR1A were negatively correlated with cancer-associated fibroblasts (CAFs) infiltration and CAFs downstream effectors. Sensitivity to specific chemotherapy regimens can be derived from gene expressions. In addition, ALOX12B and SPRR1A expression was associated with the mRNA expression of insulin like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), mammalian target of rapamycin (MTOR), and eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) in HPV negative HNSCC. Down-regulation of ALOX12B promoted HPV- HNSCC cells migration and invasion in vitro.\nCONCLUSIONS: ALOX12B and SPRR1A served as a gene signature for overall survival in HPV16- HNSCC patients, and correlated with the amount of infiltrated CAFs. The specific drug pattern was determined by the gene signature.", "claims": [{"id": "claim-method", "statement": "A univariate survival analysis (P < 0.2) was conducted to select the significant hub genes related to overall survival rate of patients in the TCGA final discovery cohort. Independent prognostic-related hub genes were identified by multivariate survival analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35768785", "locator": "sections[8] \"Prognostic-related hub gene identification and validation\" paragraph 2", "quote": "A univariate survival analysis (P < 0.2) was conducted to select the significant hub genes related to overall survival rate of patients in the TCGA final discovery cohort. Independent prognostic-related hub genes were identified by multivariate survival analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in this study are included in the article/Supplementary Material, further inquiries are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35768785", "locator": "sections[32] \"notes\" paragraph 1", "quote": "The data presented in this study are included in the article/Supplementary Material, further inquiries are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ALOX12B and SPRR1A served as a gene signature for overall survival in HPV16- HNSCC patients, and correlated with the amount of infiltrated CAFs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35768785", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "ALOX12B and SPRR1A served as a gene signature for overall survival in HPV16- HNSCC patients, and correlated with the amount of infiltrated CAFs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "ALOX12B and SPRR1A served as a gene signature for overall survival in HPV16- HNSCC patients, and correlated with the amount of infiltrated CAFs.", "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:35768785"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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Cell culture and transfection of RNA oligonucleotides HPV- HNSCC cell line", "Guangzhou, China). HPV- HNSCC cell lines was transfected with siRNA using lipofectamine™ 2000 (Invitr", "™ 2000 (Invitrogen, USA). The siRNA-mediated knockdown of ALOX12B was achieved by targeting the seq", "GCGGATGATGATG-3′. 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