NDLI: 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

Content Provider	Springer Nature : BioMed Central
Author	Li, Jing Tang, Ling-Long Ma, Jun
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). Methods 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. Results 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. Conclusions 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.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-09722-x.pdf
Ending Page	23
Page Count	23
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-022-09722-x
Journal	BMC Cancer
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-06-29
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Cancer-associated fibroblasts DNA damage response Human papilloma virus 16-negative Head and neck squamous cell carcinoma Tumor microenvironment Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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Correction: 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

SFRP1 mediates cancer-associated fibroblasts to suppress cancer cell proliferation and migration in head and neck squamous cell carcinoma

Heterogeneity of cancer-associated fibroblasts in head and neck squamous cell carcinoma.

Isolation and characterization of head and neck cancer-derived peritumoral and cancer-associated fibroblasts

AKT3 Is a Novel Regulator of Cancer-Associated Fibroblasts in Head and Neck Squamous Cell Carcinoma

Human papilloma virus circulating tumor DNA assay predicts treatment response in recurrent/metastatic head and neck squamous cell carcinoma.

The DNA Damage Response Is Differentially Involved in HPV-Positive and HPV-Negative Radioresistant Head and Neck Squamous Cell Carcinoma

The Prognostic Value of the DNA Repair Gene Signature in Head and Neck Squamous Cell Carcinoma

Discrepancy in p16 expression in patients with HPV-associated head and neck squamous cell carcinoma in Thailand: clinical characteristics and survival outcomes

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

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Correction: 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

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