Neuropilin-1 Expression Associates with Poor Prognosis in HNSCC and Elicits EGFR Activation upon CDDP-Induced Cytotoxic Stress

Napolitano, Valeria; Russo, Daniela; Morra, Francesco; Merolla, Francesco; Varricchio, Silvia; Ilardi, Gennaro; Crescenzo, Rosa Maria Di; Martino, Francesco De; Mascolo, Massimo; Celetti, Angela; Tamagnone, Luca; Staibano, Stefania

doi:10.3390/cancers13153822

Cited by 3 publications

(3 citation statements)

References 46 publications

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“…A recent investigation found that NRP1 sustained EGFR activation upon cisplatin exposure and activated downstream MAPK/AKT pathways in vitro. 24 Besides, NRP1 regulated p65-dependent proliferation signaling pathway via activating cAMP responsive element binding protein (CREB). 25 Additionally, NRP1 could enhance the migration and invasion ability of gastric cancer by activating Pi3k/Akt signaling pathway and induced 26 Yang et al demonstrated that the tumor immune evasion in cervical cancer was attributed to NRP1 that was regulated by Far upstream element binding protein 1 (FUBP1).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of NRP1 is Associated with Poor Prognosis via Accelerating Immunosuppression in Head and Neck Squamous Cell Carcinoma

Yang¹,

Teng²,

Song³

et al. 2023

IJGM

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Background Neuropilin-1 (NRP1) is a significant molecular structure that participates in many diseases progress including malignant tumors. However, its role in head and neck squamous cell carcinoma (HNSCC) remains to be uncovered. In this study, we determined the function of NRP1 as a crucial biomarker in proliferation, metastasis and immunosuppression in HNSCC. Methods We collected samples of normal tissues (n = 18) and HNSCC tissues (n = 202) for immunohistochemical staining of NRP1 and evaluated its correlation to clinical prognostic characteristics. Furthermore, we enrolled 37 HNSCC patients received immune checkpoint blockade (ICB) treatment with defined therapeutic effects records. The biological process, signal pathways, and immune infiltration relevance to NRP1 were analyzed utilized transcriptome data from The Cancer Genome Atlas (TCGA). Results The NRP1 protein expression was significantly upregulated in HNSCC tissue and was associated with T stage, N stage, histological differentiation, recurrence and NRP1 expression. The high expression of NRP1 indicated poor survival rate and was found to be an independent prognosis factor. Enrichment analysis showed that NRP1 was associated with cell adhesion, extracellular matrix organization, homophilic cell adhesion via plasma membrane in biological process and neuroactive ligand–receptor interaction, protein digestion and absorption, calcium signal pathways. Moreover, NRP1 mRNA level was found positively correlated to cancer associated fibroblast cells, Treg cells and macrophage/monocyte cells. Conclusion NRP1 might be likely to develop into a potential immunoregulation target as well as a predictive biomarker in HNSCC immune treatment.

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Section: Discussionmentioning

confidence: 99%

Overexpression of NRP1 is Associated with Poor Prognosis via Accelerating Immunosuppression in Head and Neck Squamous Cell Carcinoma

Yang¹,

Teng²,

Song³

et al. 2023

IJGM

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“…Similarly, CD86 is overexpressed in multiple cancers and associated with worse outcomes [ 61 ], while upregulation of the costimulatory molecule TNFS4 is linked to higher chemoresistance [ 62 ]. NPR1 has also been reported as a prognostic marker of worse overall survival in HNSCC [ 63 ]. Collectively, these findings may suggest higher immune evasion in the high APMHO subgroup, as CD276 [ 64 ] and other highly expressed immune markers may inhibit immune surveillance, and thus this group may benefit from checkpoint blockade.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits

Zeng,

Xie,

Pan

et al. 2023

Discov Onc

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Background Head and neck squamous cancer (HNSCC) presents variable phenotype and progression features. Clinically applicable, high-accuracy multifactorial prognostic models for HNSCC survival outcomes are warranted and an active area of research. This study aimed to construct a comprehensive prognostic tool for HNSCC overall survival by integrating cancer driver genes with tumor clinical and phenotype information. Methods Key overall survival-related cancer driver genes were screened from among main effector and reciprocal gene pairs using TCGA data using univariate Cox proportional hazard regression analysis. Independent validation was performed using the GSE41613 dataset. The main effector genes among these were selected using LASSO regression and transcriptome score modeling was performed using multivariate Cox regression followed by validation analysis of the prognostic score. Next, multivariate Cox regression analysis was performed using the transcriptome score combined with age, grade, gender, and stage. An ‘Accurate Prediction Model of HNSCC Overall Survival Score’ (APMHO) was computed and validated. Enriched functional pathways, gene mutational landscape, immune cell infiltration, and immunotherapy sensitivity markers associated with high and low APMHO scores were analyzed. Results Screening 107 overall survival-related cancer genes and 402 interacting gene pairs, 6 genes: CRLF2, HSP90AA1, MAP2K1, PAFAH1B2, MYCL and SET genes, were identified and a transcriptional score was obtained. Age, stage and transcriptional score were found to be significant predictors in Cox regression analysis and used to construct a final APMHO model showing an AUC > 0.65 and validated. Transcriptional score, age, pathologic_N, pathologic_T, stage, and TCGA_subtype were significantly different in distribution between high and low APMHO groups. High APMHO samples showed significantly higher mutation rate, enriched tumor-related pathways including Hypoxia, unfold_protein_response, Glycolysis, and mTORC1 signaling, along with differences in immune cell infiltration and immune checkpoint, interferon-γ pathway and m6A regulator expression patterns. Conclusion The APMHO score combining transcriptional and clinical variables showed good prognostic ability for HNSCC overall survival outcomes and was associated with different patterns of phenotypical features, immune and mutational landscape, and immunotherapy sensitivity marker expression. Future studies should validate this score in independent clinical cohorts.

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“…In this landscape, the epidermal growth factor receptor (EGFR) emerged from several studies. Its overexpression was found in about 90% of HNSCC cases, and it has been correlated to poor prognosis along with radiation therapy resistance [ 28 , 29 , 30 ]. Several other genes, including PIK3CA, CDKN2A, NOTCH1, MET, CCND1, PIK3CA and TP53, have been strongly correlated with HNSCC.…”

Section: Introductionmentioning

confidence: 99%

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

Arfin,

Kumar,

Lomagno

et al. 2023

Cancers

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Head and neck squamous cell carcinoma (HNSCC) is among the most common cancer worldwide, accounting for hundreds thousands deaths annually. Unfortunately, most patients are diagnosed in an advanced stage and only a percentage respond favorably to therapies. To help fill this gap, we hereby propose a retrospective in silico study to shed light on gene–miRNA interactions driving the development of HNSCC. Moreover, to identify topological biomarkers as a source for designing new drugs. To achieve this, gene and miRNA profiles from patients and controls are holistically reevaluated using protein–protein interaction (PPI) and bipartite miRNA–target networks. Cytoskeletal remodeling, extracellular matrix (ECM), immune system, proteolysis, and energy metabolism have emerged as major functional modules involved in the pathogenesis of HNSCC. Of note, the landscape of our findings depicts a concerted molecular action in activating genes promoting cell cycle and proliferation, and inactivating those suppressive. In this scenario, genes, including VEGFA, EMP1, PPL, KRAS, MET, TP53, MMPs and HOXs, and miRNAs, including mir-6728 and mir-99a, emerge as key players in the molecular interactions driving HNSCC tumorigenesis. Despite the heterogeneity characterizing these HNSCC subtypes, and the limitations of a study pointing to relationships that could be context dependent, the overlap with previously published studies is encouraging. Hence, it supports further investigation for key molecules, both those already and not correlated to HNSCC.

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Neuropilin-1 Expression Associates with Poor Prognosis in HNSCC and Elicits EGFR Activation upon CDDP-Induced Cytotoxic Stress

Cited by 3 publications

References 46 publications

Overexpression of NRP1 is Associated with Poor Prognosis via Accelerating Immunosuppression in Head and Neck Squamous Cell Carcinoma

Overexpression of NRP1 is Associated with Poor Prognosis via Accelerating Immunosuppression in Head and Neck Squamous Cell Carcinoma

A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

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