The Role of Hedgehog Signaling Pathway in Head and Neck Squamous Cell Carcinoma

Cierpikowski, Piotr; Leszczyszyn, Anna; Bar, Julia

doi:10.3390/cells12162083

Cited by 6 publications

(2 citation statements)

References 198 publications

(592 reference statements)

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“…Hedgehog signaling is involved in the development of teeth, lips, palate and salivary glands in the head and neck, and the importance of Hedgehog signaling in the occurrence of HNSCC was first reported in 2011 28 , 29 : high expression of Sonic hedgehog relates significantly to poor OS in patients with head and neck cancer. Later, Gregory et al found that Hedgehog signaling induces radiation resistance and matrix-driven tumor re-proliferation in HNSCC 30 .…”

Section: Discussionmentioning

confidence: 99%

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature

Yang,

Yang

et al. 2024

Sci Rep

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With the emergence of targeted inhibition strategies for Hedgehog signaling in cancer, multiple Hedgehog signaling pathway-related biomarkers have become the focus of research. SsGSEA algorithm was employed to analyze the Hedgehog pathway scores of samples in TCGA-HNSC dataset and divide them into two groups. Weighted co-expression network analysis was performed to identify modules strongly associated with the Hedgehog pathway. Differentially up-regulated genes in tumor samples in comparison to the normal ones were screened by Limma, in which genes belonging to modules strongly related to Hedgehog pathway were further filtered by LASSO reduction and multivariate Cox regression analysis to develop a model. ESTIMATE and CIBERSORT were served to characterize the tumor microenvironment (TME). TIDE assessed immunotherapy response. Hedgehog pathway activity was significantly higher in head and neck squamous cell carcinoma (HNSCC) tissues than in normal tissues and was correlated with HNSCC survival, glycan, cofactors and vitamins, drug metabolism, and matrix scores. Six genes (SLC2A3, EFNB2, OAF, COX4I2, MT2A and TXNRD1) were captured to form a Hedgehog associated 6-gene signature, and the resulting risk score was an independent indicator of HNSCC prognosis. It was significantly positively correlated with stromal score, metabolism, angiogenesis and inflammatory response. Patients in low-risk group with a low TIDE score had higher immunotherapy sensitivity relative to those in high-risk group. This study revealed novel findings of the Hedgehog pathway in HNSCC progression and opened up a Hedgehog pathology-related signature to help identify risk factors contributing to HNSCC progression and help predict immunotherapy outcomes.

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Section: Discussionmentioning

confidence: 99%

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature

Yang,

Yang

et al. 2024

Sci Rep

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“…However, GSK3β serves as an inhibitory factor that downregulates both pathways. In addition, SFRP1, a downstream gene of the SHH pathway, has a similar effect on the Shh and Wnt pathways ( Cierpikowski et al, 2023 ). However, the downstream GLI family of the signaling pathway can activate both of these pathways.…”

Section: Mechanisms Of Epidermal Regeneration Induced By Hfscs Under ...mentioning

confidence: 99%

Hair follicle stem cells promote epidermal regeneration under expanded condition

Zhang,

Cui,

Cang

et al. 2024

Front. Physiol.

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Skin soft tissue expansion is the process of obtaining excess skin mixed with skin development, wound healing, and mechanical stretching. Previous studies have reported that tissue expansion significantly induces epidermal proliferation throughout the skin. However, the mechanisms underlying epidermal regeneration during skin soft tissue expansion are yet to be clarified. Hair follicle stem cells (HFSCs) have been recognized as a promising approach for epidermal regeneration. This study examines HFSC-related epidermal regeneration mechanisms under expanded condition and proposes a potential method for its cellular and molecular regulation.

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Multiomics-based molecular subtyping based on the commensal microbiome predicts molecular characteristics and the therapeutic response in breast cancer

Qin,

Li,

Gao

et al. 2024

Mol Cancer

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The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared metabolic pathways and the importance of these pathways in cancer development. Based on the gut microbiota-related metabolic pathways, human gene expression profile and patient prognosis, we established a novel BC subtyping system and identified a subtype called “challenging BC”. Tumours with this subtype have more genetic mutations and a more complex immune environment than those of other subtypes. A score index was proposed for in-depth analysis and showed a significant negative correlation with patient prognosis. Notably, activation of the TPK1-FOXP3-mediated Hedgehog signalling pathway and TPK1-ITGAE-mediated mTOR signalling pathway was linked to poor prognosis in “challenging BC” patients with high scores, as validated in a patient-derived xenograft (PDX) model. Furthermore, our subtyping system and score index are effective predictors of the response to current neoadjuvant therapy regimens, with the score index significantly negatively correlated with both treatment efficacy and the number of immune cells. Therefore, our findings provide valuable insights into predicting molecular characteristics and treatment responses in “challenging BC” patients.

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The Role of Hedgehog Signaling Pathway in Head and Neck Squamous Cell Carcinoma

Cited by 6 publications

References 198 publications

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature

Hair follicle stem cells promote epidermal regeneration under expanded condition

Multiomics-based molecular subtyping based on the commensal microbiome predicts molecular characteristics and the therapeutic response in breast cancer

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