Synaptic-Adhesion Molecules Neurexin 1 and Neuroligin 1 as Novel Prognostic Factors in
Oral Squamous Cell Carcinoma

Hirohata, Hiromi; Yanagawa, Toru; Takaoka, Shohei; Uchida, Fumihiko; Shibuya, Yoichiro; Miyabe, Satoru; Tabuchi, Katsuhiko; Akagi, Yuichi; Hasegawa, Shogo; Sakai, Satoshi; Takeuchi, Yasutoshi; Ishibashi‐Kanno, Naomi; Yamagata, Kenji; Bukawa, Hiroki

doi:10.31021/jddm.20181111

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…High expression of neurexin-1 has been linked with carcinogenesis, invasion and proliferation in breast cancer [75], drug response in gastric cancer [76] and to be predictive of a worse outcome in oral squamous cell carcinoma [77]. Supporting these observations, we found that neurexin-1 expression predicts outcome in patients and affects 3D spheroid formation and resistance to cytotoxic chemotherapeutics.…”

Section: Discussionsupporting

confidence: 81%

RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma

et al. 2021

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Purpose The development of biomarkers and molecularly targeted therapies for patients with Ewing sarcoma (ES) in order to minimise morbidity and improve outcome is urgently needed. Here, we set out to isolate and characterise patient-derived ES primary cell cultures and daughter cancer stem-like cells (CSCs) to identify biomarkers of high-risk disease and candidate therapeutic targets. Methods Thirty-two patient-derived primary cultures were established from treatment-naïve tumours and primary ES-CSCs isolated from these cultures using functional methods. By RNA-sequencing we analysed the transcriptome of ES patient-derived cells (n = 24) and ES-CSCs (n = 11) to identify the most abundant and differentially expressed genes (DEGs). Expression of the top DEG(s) in ES-CSCs compared to ES cells was validated at both RNA and protein levels. The functional and prognostic potential of the most significant gene (neurexin-1) was investigated using knock-down studies and immunohistochemistry of two independent tumour cohorts. Results ES-CSCs were isolated from all primary cell cultures, consistent with the premise that ES is a CSC driven cancer. Transcriptional profiling confirmed that these cells were of mesenchymal origin, revealed novel cell surface targets for therapy that regulate cell-extracellular matrix interactions and identified candidate drivers of progression and relapse. High expression of neurexin-1 and low levels of regulators of its activity, APBA1 and NLGN4X, were associated with poor event-free and overall survival rates. Knock-down of neurexin-1 decreased viable cell numbers and spheroid formation. Conclusions Genes that regulate extracellular interactions, including neurexin-1, are candidate therapeutic targets in ES. High levels of neurexin-1 at diagnosis are associated with poor outcome and identify patients with localised disease that will relapse. These patients could benefit from more intensive or novel treatment modalities. The prognostic significance of neurexin-1 should be validated independently.

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Section: Discussionsupporting

confidence: 81%

RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma

et al. 2021

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“…NRXN1 encodes a transmembrane protein that functions as a cell adhesion molecule in synaptic transmission ( Reissner et al, 2008 ). Its high expression was observed to be associated with favorable overall survival of patients with oral cancers ( Hirohata et al, 2018 ). P2RY13 encodes a protein belongs to the family of G-protein coupled receptors, moreover, its high expression demonstrated significantly higher overall survival rates in patients with breast cancer ( Xu et al, 2020 ) and lung adenocarcinoma ( Fan et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Tumor Microenvironment-Related Prognostic Genes in Sarcoma

et al. 2021

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AimImmune cells that infiltrate the tumor microenvironment (TME) are associated with cancer prognosis. The aim of the current study was to identify TME related gene signatures related to the prognosis of sarcoma (SARC) by using the data from The Cancer Genome Atlas (TCGA).MethodsImmune and stromal scores were calculated by estimation of stromal and immune cells in malignant tumor tissues using expression data algorithms. The least absolute shrinkage and selection operator (lasso) based cox model was then used to select hub survival genes. A risk score model and nomogram were used to predict the overall survival of patients with SARC.ResultsWe selected 255 patients with SARC for our analysis. The Kaplan–Meier method found that higher immune (p = 0.0018) or stromal scores (p = 0.0022) were associated with better prognosis of SARC. The estimated levels of CD4+ (p = 0.0012) and CD8+ T cells (p = 0.017) via the tumor immune estimation resource were higher in patients with SARC with better overall survival. We identified 393 upregulated genes and 108 downregulated genes (p < 0.05, fold change >4) intersecting between the immune and stromal scores based on differentially expressed gene (DEG) analysis. The univariate Cox analysis of each intersecting DEG and subsequent lasso-based Cox model identified 11 hub survival genes (MYOC, NNAT, MEDAG, TNFSF14, MYH11, NRXN1, P2RY13, CXCR3, IGLV3-25, IGHV1-46, and IGLV2-8). Then, a hub survival gene-based risk score gene signature was constructed; higher risk scores predicted worse SARC prognosis (p < 0.0001). A nomogram including the risk scores, immune/stromal scores and clinical factors showed a good prediction value for SARC overall survival (C-index = 0.716). Finally, connectivity mapping analysis identified that the histone deacetylase inhibitors trichostatin A and vorinostat might have the potential to reverse the harmful TME for patients with SARC.ConclusionThe current study provided new indications for the association between the TME and SARC. Lists of TME related survival genes and potential therapeutic drugs were identified for SARC.

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“…Neurexin-3 protein which is encoded by NRXN3 gene takes a role in cell adhesion and cell recognition and modulates intracellular signaling. It has been reported that polymorphism of NRXN3 gene (rs10146997) and mutations of NRXN3 gene are related with higher breast cancer risk [21,22]. Forkhead box protein Q1 (FOXQ1) is a transcription factor and takes a role in cancer, aging and development.…”

Section: Resultsmentioning

confidence: 99%

Analysis of miRNA-Mediated ceRNAs In The Pathogenesis of Renal Cell Carcinoma: An In Silico Approach

Avşar

2020

Hittite J. Sci. Eng.

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R enal cell tumors represent approximately 3% of all cancers in males and lower incidence in females. Several factors such as genetics, obesity, tobacco smoking, hypertension, diuretics, medications such as acetaminophen and non-aspirin non-steroidal anti-inflammatory drugs, viral hepatitis, and chemical carcinogens (asbestos, arsenic, etc.,) are implicated in the pathogenesis of renal cell tumors [1, 2, 3]. Renal cell carcinomas are divided into three subtypes: chromophobe, renal clear cell carcinoma and renal papillary cell carcinoma and this classification is verified by genetic and cytogenetic analysis [4, 5]. The most common form of renal cell tumors (approximately 70% of renal tumors) is renal clear cell carcinoma in adults. Papillary renal cell carcinoma is the second most frequent kidney tumors in adults [6].

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Synaptic-Adhesion Molecules Neurexin 1 and Neuroligin 1 as Novel Prognostic Factors in Oral Squamous Cell Carcinoma

Cited by 3 publications

References 27 publications

RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma

RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma

Identification of Tumor Microenvironment-Related Prognostic Genes in Sarcoma

Analysis of miRNA-Mediated ceRNAs In The Pathogenesis of Renal Cell Carcinoma: An In Silico Approach

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