Predictive Role of NEK6 in Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Yang, Zhimin; Liao, Bing; Yang, Sisi; Su, Tian; Wang, Weiming

doi:10.3389/fendo.2022.943686

Cited by 3 publications

(5 citation statements)

References 26 publications

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“…The risk gene NEK6 encodes protein kinase which plays a role in apoptosis, cell cycle regulation, chemoresistance, and telomere maintenance [71]. NEK6 genes promote cell proliferation and develop head neck squamous cell carcinoma [72]. In addition, our study also highlighted that among the ten differentially expressed genes, three genes ( PMF1 , SH3PXD2A , ACAD10 ) were modulated by DNA methylation and gene expression in Europeans (SNP→DNA methylation→Gene expression→Stroke) and six genes ( HTRA1 , PMF1 , FBN2 , C9orf84 , SH3PXD2A , ACAD10 ) were modulated by DNA methylation and gene expression in trans-ethnic ancestry group (SNP→DNA methylation→Gene expression→Stroke).However, we demonstrated their causal and functional insights as they could be modulated through DNA methylations, which could influence gene expression.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Integration of Mendelian randomisation and systems biology models to identify novel blood-based biomarkers for stroke

Islam

Rahman

Khan

et al. 2023

Preprint

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Stroke is the second largest cause of mortality in the world. Genome-wide association studies (GWAS) have identified some genetic variants associated with stroke risk, but their putative functional causal genes are unknown. Hence, we aimed to identify putative functional causal gene biomarkers of stroke risk. We used a summary-based Mendelian randomisation (SMR) approach to identify the pleiotropic associations of genetically regulated traits (i.e., gene expression and DNA methylation) with stroke risk. Using SMR approach, we integrated cis-expression quantitative loci (cis-eQTLs) and cis-methylation quantitative loci (cis-mQTLs) data with GWAS summary statistics of stroke. We also utilised heterogeneity in dependent instruments (HEIDI) test to distinguish pleiotropy from linkage from the observed associations identified through SMR analysis. Our integrative SMR analyses and HEIDI test revealed 45 candidate biomarker genes (FDR < 0.05; PHEIDI>0.01) that were pleiotropically or potentially causally associated with stroke risk. Of those candidate biomarker genes, 10 genes (HTRA1, PMF1, FBN2, C9orf84, COL4A1, BAG4, NEK6, SH2B3, SH3PXD2A, ACAD10) were differentially expressed in genome-wide blood transcriptomics data from stroke and healthy individuals (FDR<0.05). Functional enrichment analysis of the identified candidate biomarker genes revealed gene ontologies and pathways involved in stroke, including cell aging, metal ion binding and oxidative damage. Based on the evidence of genetically regulated expression of genes through SMR and directly measured expression of genes in blood, our integrative analysis suggests ten genes as blood biomarkers of stroke risk. Furthermore, our study provides a better understanding of the influence of DNA methylation on the expression of genes linked to stroke risk.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integration of Mendelian randomisation and systems biology models to identify novel blood-based biomarkers for stroke

Islam

Rahman

Khan

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…NEK6/LHX2 locus was associated with typical nAMD, but exhibited a much weaker signal for PCV. NEK6 expression was induced by hypoxia in a Hif1a-dependent manner 65 and involved in key angiogenic pathways 66 . LHX2 has been reported to activate mTOR and PDGF signaling, pathways associated with nAMD 67 , 68 .…”

Section: Discussionmentioning

confidence: 99%

Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes

Fan,

Li,

Wang

et al. 2023

Nat Commun

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Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ($$P \, < \, 1.19\times {10}^{-8}$$ P < 1.19 × 10 − 8 ). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; $$P=1.05\times {10}^{-6}$$ P = 1.05 × 10 − 6 ) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

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“…Furthermore, the disease response rate at 24 weeks reached 16% (25% in PD-L1 positive patients), and adverse reactions were reported in only 7% of patients, with no treatment-related deaths recorded. Currently, Durvalumab is progressing through Phase III clinical trials, evaluating various monotherapy and combination therapy approaches in the treatment of HNSCC [ 58 , 59 ].…”

Section: Hnscc-related Immunotherapymentioning

confidence: 99%

“…In contrast to the well-known immunosuppressive mechanism of PD-1/PD-L1, CTLA-4 inhibitors often enhance immune responses, leading to improved immune cell-mediated killing of cancer cells. However, this enhancement is often accompanied by more toxic side effects [ 58 , 59 ].…”

Section: Hnscc-related Immunotherapymentioning

confidence: 99%

Exploring the frontiers: tumor immune microenvironment and immunotherapy in head and neck squamous cell carcinoma

Liu,

Wang,

Fang

2024

Discov Onc

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The global prevalence of head and neck malignancies positions them as the sixth most common form of cancer, with the head and neck squamous cell carcinoma (HNSCC) representing the predominant histological subtype. Despite advancements in multidisciplinary approaches and molecular targeted therapies, the therapeutic outcomes for HNSCC have only marginally improved, particularly in cases of recurrent or metastatic HNSCC (R/MHNSCC). This situation underscores the critical necessity for the development of innovative therapeutic strategies. Such strategies are essential not only to enhance the efficacy of HNSCC treatment but also to minimize the incidence of associated complications, thus improving overall patient prognosis. Cancer immunotherapy represents a cutting-edge cancer treatment that leverages the immune system for targeting and destroying cancer cells. It's applied to multiple cancers, including melanoma and lung cancer, offering precision, adaptability, and the potential for long-lasting remission through immune memory. It is observed that while HNSCC patients responsive to immunotherapy often experience prolonged therapeutic benefits, only a limited subset demonstrates such responsiveness. Additionally, significant clinical challenges remain, including the development of resistance to immunotherapy. The biological characteristics, dynamic inhibitory changes, and heterogeneity of the tumor microenvironment (TME) in HNSCC play critical roles in its pathogenesis, immune evasion, and therapeutic resistance. This review aims to elucidate the functions and mechanisms of anti-tumor immune cells and extracellular components within the HNSCC TME. It also introduces several immunosuppressive agents commonly utilized in HNSCC immunotherapy, examines factors influencing the effectiveness of these treatments, and provides a comprehensive summary of immunotherapeutic strategies relevant to HNSCC.

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Predictive Role of NEK6 in Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Cited by 3 publications

References 26 publications

Integration of Mendelian randomisation and systems biology models to identify novel blood-based biomarkers for stroke

Integration of Mendelian randomisation and systems biology models to identify novel blood-based biomarkers for stroke

Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes

Exploring the frontiers: tumor immune microenvironment and immunotherapy in head and neck squamous cell carcinoma

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