A neural‐related gene risk score for head and neck squamous cell carcinoma

Tao, Zhuo-Ying; Yang, Wei‐En; Zhu, Wangyong; Wang, Leilei; Li, Kar Yan; Guan, Xin‐Yuan; Su, Yu‐xiong

doi:10.1111/odi.14434

Cited by 4 publications

(2 citation statements)

References 101 publications

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“…Subsequently, the intersecting DEGs (IDEGs) were screened for detailed analysis using the Venn diagram, and five genes, including DKK1, BASP1, FAP, INHBA, and ITGA5, were screened (Figure 3A). BASP1, FAP, INHBA, and ITGA5 had been reported to be upregulated in several cancers and could regulate neuronal activity, [13][14][15][16][17] but their relationship with DKK1, nerves, and HNSCC still remains unknown.…”

Section: Dkk1 Is Overexpressed In Most Hnscc Cells and Tissuesmentioning

confidence: 99%

Dickkopf‐1 drives perineural invasion via PI3K–AKT signaling pathway in head and neck squamous cancer

Wang,

Li,

Liang

et al. 2024

MedComm

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Perineural invasion (PNI) leads to the poor prognosis of head and neck squamous cancer (HNSCC) patients, but the mechanism of PNI remains unclear. Dickkopf‐1 (DKK1), a secretory protein in the Wnt signaling pathway, was found indeed upregulated in HNSCC cells and tissues. Higher expression of DKK1 was statistically relevant to T stage, N stage, PNI, and poor prognosis of HNSCC. DKK1 overexpression enhanced the migration abilities of cancer cells. Moreover, DKK1‐overexpressing cancer cells promoted cancer cells invasion of peripheral nerves in vitro and in vivo. Mechanistically, DKK1 could promote the PI3K–AKT signaling pathway. The migration abilities of neuroblastoma cells, which were enhanced by DKK1‐overexpressing HNSCC cell lines, could be reversed by an inhibitor of Akt (MK2206). The association of DKK1 with PNI was also confirmed in HNSCC samples. Variables, including T stage, N stage, DKK1 expression, and PNI, were used to establish a nomogram to predict the survival probability and disease‐free probability at 3 and 5 years. In summary, DKK1 can promote the PI3K–AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.

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Section: Dkk1 Is Overexpressed In Most Hnscc Cells and Tissuesmentioning

confidence: 99%

Dickkopf‐1 drives perineural invasion via PI3K–AKT signaling pathway in head and neck squamous cancer

Wang,

Li,

Liang

et al. 2024

MedComm

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“…A recent study has demonstrated that the high expression of nerve growth factor receptors on tumor cells predicts anti-PD-1 therapy resistance in patients with melanoma ( 11 ), which provides evidence for the correlation between neural signaling and immunotherapy responses. Interestingly, our previous bioinformatic analysis on head and neck cancer transcriptome data from The Cancer Genome Atlas revealed that the neural-related differential expressed genes (DEG) had a predictive role in both the survival and the benefit of immunotherapy in head and neck squamous cell carcinoma (HNSCC; 12 ). Issues awaiting clarification include the underlying mechanisms for the nerve-tumor cross-talk leading to tumor progression and immunotherapy resistance in OSCC.…”

Section: Introductionmentioning

confidence: 99%

Lingual Denervation Improves the Efficacy of Anti-PD-1 Immunotherapy in Oral Squamous Cell Carcinomas by Downregulating TGFβ Signaling

Tao,

Wang,

Zhu

et al. 2024

Cancer Research Communications

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Aims: Intratumoral nerve infiltration relates to tumor progression and poor survival in oral squamous cell carcinoma (OSCC). How neural involvement regulates anti-tumor immunity has not been well characterized. This study aims to investigate molecular mechanisms of regulating tumor aggressiveness and impairing anti-tumor immunity by nerve-derived factors. Methods: We performed the surgical lingual denervation in an immunocompetent mouse OSCC model to investigate its effect on tumor growth and the efficacy of anti-PD-1 immunotherapy. A trigeminal ganglion neuron and OSCC cell co-culture system was established to investigate the proliferation, migration and invasion of tumor cells and the PD-L1 expression. Both the neuron-tumor cell co-culture in vitro model and the OSCC animal model were explored. Results: Lingual denervation slowed down tumor growth and improved the efficacy of anti-PD-1 treatment in the OSCC model. Coculturing with neurons not only enhanced the proliferation, migration and invasion but also upregulated TGFβ-Smad2 signaling and PD-L1 expression of tumor cells. Treatment with the TGFβ signaling inhibitor galunisertib reversed nerve-derived tumor aggressiveness and down-regulated PD-L1 on tumor cells. Similarly, lingual denervation in vivo decreased TGFβ and PD-L1 expression and increased CD8+ T cell infiltration and the expression of IFNγ and TNFα within tumor. Conclusions: Neural involvement enhanced tumor aggressiveness through upregulating TGFβ signaling and PD-L1 expression in OSCC, while denervation of OSCC inhibited tumor growth, down-regulated TGFβ signaling, enhanced activities of CD8+ T cells and improved the efficacy of anti-PD-1 immunotherapy. This study will encourage further research focusing on denervation as a potential adjuvant therapeutic approach in OSCC.

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ITGA5 is associated with prognosis marker and immunosuppression in head and neck squamous cell carcinoma

Liu,

Wang,

Chen

et al. 2024

Diagn Pathol

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Background Head and neck squamous cell carcinoma (HNSCC) is a major tumor that seriously threatens the health of the head and neck or mucosal system. It is manifested as a malignant phenotype of high metastasis and invasion caused by squamous cell transformation in the tissue area. Therefore, it is necessary to search for a biomarker that can systematically correlate and reflect the prognosis of HNSCC based on the characteristics of head and neck tumors. Methods Based on TCGA-HNSCC data, R software was used to analyze gene expression, correlation, Venn diagram, immune invasive and immunosuppressive phenotypes respectively. The intrinsic effect of ITGA5 on the malignant phenotype of HNSCC cells was verified by cell experiments. Immunohistochemical images from The Human Protein Atlas (THPA) database display the differences in the expression of related proteins in HNSCC tissues. Based on functional enrichment and correlation analysis, the prognostic value of ITGA5 for HNSCC was explored, and the expression level of ITGA5 may affect the chemotherapy of targeting the PI3K-AKT. Results In this study, the target gene ITGA5 may be identified as a valuable prognostic marker for HNSCC. The results of enrichment analysis showed that ITGA5 was mainly involved in the dynamic process of extracellular matrix, which may affect the migration or metastasis of tumor cells. Meanwhile, ITGA5 may be closely related to the infiltration of M2 macrophages, and its secretory phenotypes TGFB1, PDGFA and PDGFB may affect the immunosuppressive phenotypes of tumor cells, which reflects the systemic influence of ITGA5 in HNSCC. In addition, the expression levels of ITGA5 were negatively correlated with the efficacy of targeting PI3K-AKT chemotherapy. Conclusion ITGA5 can be used as a potential marker to systematically associate with prognosis of HNSCC, which may be associated with HNSCC malignant phenotype, immunosuppression and chemotherapy resistance. Supplementary Information The online version contains supplementary material available at 10.1186/s13000-024-01559-1.

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A neural‐related gene risk score for head and neck squamous cell carcinoma

Cited by 4 publications

References 101 publications

Dickkopf‐1 drives perineural invasion via PI3K–AKT signaling pathway in head and neck squamous cancer

Dickkopf‐1 drives perineural invasion via PI3K–AKT signaling pathway in head and neck squamous cancer

Lingual Denervation Improves the Efficacy of Anti-PD-1 Immunotherapy in Oral Squamous Cell Carcinomas by Downregulating TGFβ Signaling

ITGA5 is associated with prognosis marker and immunosuppression in head and neck squamous cell carcinoma

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