Early Nasopharyngeal Carcinoma Research Articles

Effect of endoscopic surgery combined with chemotherapy and radiotherapy on prognosis of early nasopharyngeal carcinoma patients in high incidence area

Objective:To investigate the differences in the therapeutic effects of endoscopic surgery combined with chemotherapy and endoscopic surgery combined with radiotherapy in the treatment of early nasopharyngeal carcinoma, and to select individualized treatment strategy for early nasopharyngeal carcinoma. Methods:The clinical data of 68 patients with early nasopharyngeal carcinoma（T1-2N₀M₀） who received surgical treatment in a high-incidence area were retrospectively analyzed. According to different treatment methods, they were divided into the surgery + chemotherapy group（n=34, treated with endoscopic surgery combined with chemotherapy） and the surgery + radiotherapy group（n=34, treated with endoscopic surgery combined with radiotherapy）. Propensity score matching was used to match the patient data between the two groups at a 1∶1 ratio. Patients were followed up, and the survival rates and hematological toxicities were compared between the two groups. Results:Twenty-four cases in the surgery + chemotherapy group and 24 cases in the surgery + radiotherapy group were successfully matched. After matching, there was no statistically significant difference in T stage, and clinical stage between the two groups（all P>0.05）. The 3-year OS and DFS in the surgery + chemotherapy group were 100.0% and 95.8%, respectively, while the 3-year OS and DFS in the surgery + radiotherapy group were 100.0% and 100.0%, respectively, with no significant difference in survival rates between the two groups（both P>0.05）. After treatment, there was no statistically significant difference in bone marrow suppression between the surgery + chemotherapy group and the surgery + radiotherapy group （all P> 0.05） Conclusion:Endoscopic surgery combined with chemotherapy and surgery combined with radiotherapy have comparable clinical efficacy in the treatment of early nasopharyngeal carcinoma, but without radiotherapy-related complications, which is worth further investigation.

Early detection of nasopharyngeal carcinoma through machine-learning-driven prediction model in a population-based healthcare record database.

Early diagnosis and treatment of nasopharyngeal carcinoma (NPC) are vital for a better prognosis. Still, because of obscure anatomical sites and insidious symptoms, nearly 80% of patients with NPC are diagnosed at a late stage. This study aimed to validate a machine learning (ML) model utilizing symptom-related diagnoses and procedures in medical records to predict nasopharyngeal carcinoma (NPC) occurrence and reduce the prediagnostic period. Data from a population-based health insurance database (2001-2008) were analyzed, comparing adults with and without newly diagnosed NPC. Medical records from 90 to 360 days before diagnosis were examined. Five ML algorithms (Light Gradient Boosting Machine [LGB], eXtreme Gradient Boosting [XGB], Multivariate Adaptive Regression Splines [MARS], Random Forest [RF], and Logistics Regression [LG]) were evaluated for optimal early NPC detection. We further use a real-world data of 1 million individuals randomly selected for testing the final model. Model performance was assessed using AUROC. Shapley values identified significant contributing variables. LGB showed maximum predictive power using 14 features and 90 days before diagnosis. The LGB models achieved AUROC, specificity, and sensitivity were 0.83, 0.81, and 0.64 for the test dataset, respectively. The LGB-driven NPC predictive tool effectively differentiated patients into high-risk and low-risk groups (hazard ratio: 5.85; 95% CI: 4.75-7.21). The model-layering effect is valid. ML approaches using electronic medical records accurately predicted NPC occurrence. The risk prediction model serves as a low-cost digital screening tool, offering rapid medical decision support to shorten prediagnostic periods. Timely referral is crucial for high-risk patients identified by the model.

Prediction of cervical lymph nodes recurrence after radiotherapy for early nasopharyngeal carcinoma via unsupervised diagnostic feature learning and supervised ensemble classifier learning

Purpose:Nasopharyngeal carcinoma is one of the most prevalent malignant tumors in Guangdong, China. In the field of medicine, predicting the recurrence of early-stage nasopharyngeal carcinoma after radiotherapy holds significant importance. Our objective was to develop a novel classification model aimed at predicting recurrence following radiotherapy for early nasopharyngeal carcinoma. Methods and Materials:This paper introduces an innovative approach by combining unsupervised diagnostic feature learning (biclustering algorithm) with Adaboost ensemble learning to create a novel classification model. Notably, the nasopharyngeal carcinoma dataset underwent biclustering algorithm application for the first time. Initially, the Borderline-SMOTE oversampling algorithm was employed to address the dataset’s imbalance issue. Subsequently, the biclustering algorithm, which is based on an improved multi-objective genetic algorithm (NSGA-II), was utilized to seek bicluster outcomes exhibiting consistent representation patterns. The attributes of these bicluster outcomes were assessed and employed as diagnostic rules for constructing weak classifiers. Ultimately, the Adaboost ensemble learning technique was employed to amalgamate the weak classifiers into a robust classifier. Results:Following the application of 10-fold cross-validation, the model exhibited an accuracy of 80.33%, sensitivity of 79.55%, specificity of 80.43%, and GMean of 79.99%, accompanied by an AUC value of 0.904. Conclusions:The presented classification model outperformed alternative classification models in terms of classification accuracy and generalization when applied to the nasopharyngeal carcinoma dataset. Consequently, it serves as a valuable tool to aid medical professionals in predicting the likelihood of recurrence in the cervical lymph nodes following radiotherapy for early-stage nasopharyngeal carcinoma.

Quality of life and swallowing outcomes after early proactive swallowing rehabilitation by either transcutaneous neuromuscular electrical stimulation or exercise-based swallowing training in patients with nasopharyngeal carcinoma after radiotherapy.

Exercise-based swallowing training (EBST) and transcutaneous neuromuscular electrical stimulation (TNMES) are common modalities used to treat late dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC). We aimed to investigate and compare the efficacies of EBST and TNMES as proactive treatments administered early after radiotherapy. Patients with early post-radiotherapy NPC (n = 120) underwent either TNMES or EBST. Flexible endoscopic evaluation of swallowing (FEES), quality of life (QOL), and swallowing function questionnaires were completed before the intervention as well as immediately, 6, and 12 months after the intervention. Outcome measures included the scores for the swallowing function score (SFS), penetration and aspiration scale (PAS), dynamic imaging grade of swallowing toxicity (DIGEST), functional oral intake scale (FOIS), swallowing performance status scale (SPSS), pharyngeal motor impairment (PMI), pharyngeal function impairment (PFI), and functional assessment after cancer therapy-nasopharyngeal (FACT-NP) questionnaire. Three months after radiotherapy, 31 and 34 patients underwent TNMES and EBST, respectively, and completed swallowing assessments at all four assessment timepoints. All patients showed post-radiotherapy impairments in the SFS, PAS, DIGEST, PMI, and PFI. Compared with the EBST group, the TNMES group showed significant improvements in the PFI and PMI scores, with small-to-medium effect sizes. Additionally, compared with the EBST group, the TNMES group demonstrated a trend toward slightly better improvements in the PAS, DIGEST, FOIS, and SPSS scores immediately and 6 months after the intervention. The SFS scores improved from baseline in both groups; however, the TNMES group showed an earlier improvement. Finally, the TNMES group showed better QOL according to the FACT-NP than the EBST group. Proactive TMNES and EBST are safe and feasible modalities for improving swallowing in patients with NPC when administered early after radiotherapy. Although TNMES showed better results than EBST, these results should be interpreted with caution given the study limitations. 1B.

MSU-Net: Multi-scale Sensitive U-Net based on pixel-edge-region level collaborative loss for nasopharyngeal MRI segmentation

Radiotherapy is the traditional treatment of early nasopharyngeal carcinoma (NPC). Automatic accurate segmentation of risky lesions in the nasopharynx is crucial in radiotherapy. U-Net has been proved its effective medical image segmentation ability. However, the great difference in the structure and size of nasopharynx among different patients requires a network that pays more attention to multi-scale information. In this paper, we propose a multi-scale sensitive U-Net (MSU-Net) based on pixel-edge-region level collaborative loss (LCo−PER) for NPC segmentation task. A series of novel feature fusion modules based on spatial continuity and multi-scale semantic are proposed for extracting multi-level features while efficiently searching for all size lesions. A spatial continuity information extraction module (SCIEM) is proposed for effectively using the spatial continuity information of context slices to search small lesions. And a multi-scale semantic feature extraction module (MSFEM) is proposed for extracting features of different receptive fields. LCo−PER is proposed for the network training which makes network model could take into account the size of different lesions. The global Dice, Precision, Recall and IOU of the testing set are 84.50%, 97.48%, 84.33% and 82.41%, respectively. The results show that our method is better than the other state-of-the-art methods for NPC segmentation which obtain higher accuracy and effective segmentation performance.

Prediction of Potential Biomarkers in Early-Stage Nasopharyngeal Carcinoma Based on Platelet RNA Sequencing

Early diagnosis is essential for the treatment and prevention of nasopharyngeal cancer. However, there is a lack of effective biological indicators for nasopharyngeal carcinoma (NPC). Therefore, we explored the potential biomarkers in tumour-educated blood platelet (TEP) RNA in early NPC. Platelets were isolated from blood plasma and their RNA was extracted. High-throughput sequenced data from a total of 33 plasma samples were analysed using DESeq2 to identify the differentially expressed genes (DEGs). Subsequently, the DEGs were subjected to principal component analysis (PCA), gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; and Cytoscape, TargetScan, and miRanda software were used for inferring the competing endogenous RNA network. We identified 19 long non-coding (lnc) RNAs (DElncRNAs) and 248 mRNAs (DEmRNAs) that were differentially expressed in the TEP RNA. In addition, SELP gene mRNA and lncRNAs AC092135.3, AC012358.2, AL021807.1, AP001972.5, and GPX1 were found to be down-regulated DEmRNA and DElncRNAs in the early stage of NPC. Bioinformatic analysis showed that these DEmRNAs and DElncRNAs may be involved in regulating the pathogenesis of NPC. Our research may provide new insights for exploring the biological mechanisms of NPC and early diagnosis using potential biomarkers.

Repression of DERL3 via DNA methylation by Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is Epstein-Barr virus (EBV)-associated invasive malignancy. Increasing evidence indicates that epigenetic abnormalities, including DNA methylation, play important roles in the development of NPC. In particular, the EBV principal oncogene, latent membrane protein 1 (LMP1), is considered a key factor in inducing aberrant DNA methylation of several tumour suppressor genes in NPC, although the mechanism remains unclear. Herein, we comprehensively analysed the methylome data of Infinium BeadArray from 51 NPC and 52 normal nasopharyngeal tissues to identify LMP1-inducible methylation genes. Using hierarchical clustering analysis, we classified NPC into the high-methylation, low-methylation, and normal-like subgroups. We defined high-methylation genes as those that were methylated in the high-methylation subgroup only and common methylation genes as those that were methylated in both high- and low-methylation subgroups. Subsequently, we identified 715 LMP1-inducible methylation genes by observing the methylome data of the nasopharyngeal epithelial cell line with or without LMP1 expression. Because high-methylation genes were enriched with LMP1-inducible methylation genes, we extracted 95 high-methylation genes that overlapped with the LMP1-inducible methylation genes. Among them, we identified DERL3 as the most significantly methylated gene affected by LMP1 expression. DERL3 knockdown in cell lines resulted in significantly increased cell proliferation, migration, and invasion. Lower DERL3 expression was more frequently detected in the advanced T-stage NPC than in early T-stage NPC. These results indicate that DERL3 repression by DNA methylation contributes to NPC tumour progression.

Tumor Microbiome in Nasopharyngeal Carcinoma and Its Association With Prognosis.

IntroductionPrevious studies have reported a close relationship between cancer and microbes, particularly gut and tumor microbiota; however, the presence of tumor microbiome in nasopharyngeal carcinoma (NPC) and its role in the prognosis of NPC remain unclear.MethodsWe collected 64 samples including tissues from 50 patients with NPC (NPC group) and 14 patients with chronic nasopharyngitis (control group) receiver operating characteristics and we applied 16S ribosome RNA gene sequencing of all samples to assess microbiome profiles and immunohistochemistry to detect tumor microbiome in NPC.ResultsPatients in the control group harbored higher species diversity than those in the NPC group; however, the beta diversity was more distinct in the NPC group. In total, three genera with statistically significant differences between the two groups were identified. The area under the receiver operating characteristics (ROC) curve (AUC) was calculated using the relative abundance of these three significant genera, and a value of 0.842 was achieved. Furthermore, Turicibacter was confirmed as a potentially independent prognostic factor for NPC patients, and the progression-free survival (PFS) was markedly prolonged in patients with a low relative abundance of Turicibacter compared to patients with a high relative abundance of this genus (cutoff: 0.0046, hazard ratio: 5.10, 95% confidence interval: 2.04–12.77, p = 0.004).ConclusionsThe present study provided strong evidence of a correlation between tumor microbiome and NPC; the tumor microbiome may be considered a biomarker for early NPC diagnosis. Turicibacter potentially served as a independently prognostic indicator for NPC patients.

Selected Articles from This Issue

Malignant pleural mesothelioma (MPM) is a highly aggressive cancer that lacks effective therapeutic options, owing to chemotherapeutic resistance and lack of currently targetable oncogenic mutations. However, mutations in histone modifiers documented in Mp. represent exciting potential therapeutic targets. Wirawan and colleagues used estrogen receptor sensitive Snail variant mesenchymal and sarcomatoid-like MPM cell lines to show that lysine-specific demethylase 1 (LSD1) drives a MPM mesenchymal phenotype, tumor cell migration, and cisplatin resistance. The authors integrated microarray, phospho-kinase array, and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses to identify milk fat globulin protein E8 (MFGE8) as the LSD1-mediated driver of cisplatin resistance. Subsequent experiments demonstrated that MFGE8 interaction with integrin β3 drives FAK and AKT phosphorylation, initiating a positive feedback loop that upregulates Snail expression and promotes its associated mesenchymal phenotype. In sum, the work presented suggests that LSD1 may be a multifactorial therapeutic target for MPM.While androgen deprivation can provide at least temporary benefit for men with metastatic prostate cancer, most patients go on to develop lethal castration-resistant prostate cancer (CRPC). Speckle-type POZ protein (SPOP) mutations and Sonic hedgehog (SHH)-mediated androgen receptor (AR) signaling activation are prevalent in CRPC, making each therapeutic targets of interest for the disease. In their study, Burleson and colleagues demonstrate that a transcriptional activator of the SHH pathway, GLI3, enhances SHH signaling and cell proliferation in androgen-deprived prostate cancer cells. The authors show that GLI3 is post-translationally stabilized by somatic SPOP mutations, and that stabilized GLI3 partners with AR to induce a gene expression program that promotes tumor cell proliferation in vitro and in vivo. CRPC patients whose tumors expressed the GLI3 gene signature displayed higher biochemical relapse rates, suggesting that the signature may identify patients at high risk of disease progression. Overall, the presented data provide a novel mechanistic link between SPOP mutations and SHH-mediated AR signaling activation that could inform prognostic and therapeutic strategies for CRPC moving forward.The efficacy of antiangiogenic cancer therapies has been limited by side effects and therapeutic resistance, suggesting that targeting angiogenesis alongside other oncogenic processes may be more effective than targeting angiogenesis alone. Recent work linking low IQ motif-containing GTPase-activating protein 2 (IQGAP2) expression to breast tumor epithelial–mesenchymal transition (EMT), angiogenesis, and poor patient outcomes makes IQGAp. an intriguing therapeutic candidate. Kumar and colleagues used IQGAP2 ablation and overexpression in both estrogen receptor-positive and -negative breast cancer cell lines to demonstrate that IQGAP2 reduction in those cell lines increases endothelial cell proliferation and migration. Accordingly, IQGAP2 reduction increased vascular density in chick chorioallantoic membranes and wound healing assays, which supported the authors' observation that IQGAP2 expression inversely correlated with endothelial cell abundance in tumor cells from breast cancer patients. The authors mechanistically attributed their findings to increased ERK-VEGF-A signaling in tumor cells, which activated VEGFR2-AKT signaling in endothelial cells. Results from the study position IQGAP2 as a next-generation anti-angiogenic therapeutic target potentially capable of simultaneously inhibiting angiogenesis and EMT.Draining lymph node metastasis is often noted upon nasopharyngeal carcinoma (NPC) diagnosis, and can mark an initial stage of progressive metastatic dissemination. While Epstein-Barr virus (EBV) has long been associated with NPC, its role in initial metastatic processes has not been defined. In their study, Li and colleagues used EBV-infected and functional EBV knockout NPC cell lines to demonstrate that EBV-positive NPC induces lymphatic endothelial cell proliferation and migration. Gene expression analysis revealed elevated VEGF-C expression in NPC infected with EBV, and the authors showed that VEGF-C was responsible for EBV-induced lymphangiogenesis. Further work demonstrated that EBV miRNA BART15 targets PHLPP1 in NPC cells, resulting in increased AKT phosphorylation, HIF-1α activation, and VEGF-C production. Moreover, patients with EBV-positive NPC displayed higher levels of lymphangiogenesis and lymph node metastasis. Taken together, the presented work sheds light on how EBV induces early NPC progression and elucidates a molecular pathway that could be therapeutically targeted.

The mechanism of miR-410-3p and miR-34c in nasopharyngeal carcinoma development and progression.

To investigate the relationship between miR-410-3p, miR-34c and nasopharyngeal carcinoma development, we detected the expression of miR-410-3p and miR-34c in nasopharyngeal carcinoma tissues and evaluate its clinical value as a molecular marker for predicting the prognosis in patients with nasopharyngeal carcinoma through clinical case study. To identify the role and mechanism of miR-410-3p and miR-34c in nasopharyngeal carcinoma development and progression. The expression of miR-410-3p and miR-34cin 300 cases of nasopharyngeal carcinoma tissues and 30 cases of paired adjacent normal breast tissues was detected by RT-qPCR. The paired t-test was used to compare the differences of miR-410-3pand miR-34c levels between the nasopharyngeal carcinoma and normal groups. The Chi-square test was used to compare the differences between miR-410-3p and miR-34c expression and clinicopathological factors. The Kaplan-Meier survival curve was used to analyze the relationship between miR-410-3p and miR-34c expression and 5-year overall survival (OS). The Cox proportional hazards regression model was used to evaluate the prognostic value. The results were validated by TCGA database. The expression of miR-410-3p was down-regulated in nasopharyngeal carcinoma tissues compared with that of paired normal tissues (P<0.001). The patients with lower miR-410-3p expression have a higher ratio of positive lymph node status (P=0.039) and a poorer 5-year disease-free survival (P=0.001) and 5-year overall survival (P = 0.002). The expression of mi R-34c was down-regulated in nasopharyngeal carcinoma tissues compared with that of paired normal tissues (P<0.001). Up-regulation of the miR-34c inhibited the viability of paired normal tissues (P<0. 01), but there was no significant change in migration of the paired normal tissues. Downregulation of mi R-34c promoted the viability and migration of paired normal tissues (P<0. 05). The expression of miR-410-3p and miR-34c levels are predictors for the OS in patients with nasopharyngeal carcinoma. The expression of miR-410-3p and miR-34c are molecular markers of early nasopharyngeal carcinoma metastasis and an independent prognostic biomarker for patients with nasopharyngeal carcinoma.

Clinicopathological Significance of ATRX Expression in Nasopharyngeal Carcinoma Patients: A Retrospective Study.

Background: Nasopharyngeal carcinoma (NPC) is the most common head and neck squamous cell carcinoma in south China. Radiation technology improves the local control rates in early NPC. However, the distant metastases are still the main cause of treatment failure. Thus, to find biomarkers for prognosis will help to enhance the survival of NPC. ATRX is a chromatin remodeling protein localized in the nucleus. Deletion or mutation of ATRX gene has been demonstrated in a variety of malignancies. However, the significance of ATRX expression in the prognosis of NPC remains unclear.Methods: Tumor tissues from 227 NPC patients diagnosed in the Second Xiangya Hospital of Central South University from 2011 to 2016 were selected. Immunohistochemistry was used to detect the ATRX expression level of the tumor tissue. Chi-square test was used to analyze the relationship between ATRX expression and clinical characteristics such as age, sex, T stage, N stage and clinical stage. Kaplan-Meier method was used for survival analysis, and log-rank was used to compare the difference in survival rate.Results: There were 53 patients with negative ATRX expression, accounting for 24.2% of the total group. ATRX expression was not significantly associated with age, sex, N stage, clinical stage, and progression-free survival (PFS) (P>0.05). However, patients with negative ATRX expression had earlier T staging (P=0.045) and a higher 5-year overall survival (84.9% vs 66.9%, P=0.022).Conclusions: Loss of ATRX expression may contribute to better prognosis in patients with NPC.

Effects of Surgery Combined with Chemoradiotherapy on Short- and Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma.

ObjectiveThe efficacy of surgery as the primary treatment modality for nasopharyngeal carcinoma (NPC) is yet to be clarified. Therefore, we aimed to explore the short- and long-term efficacy of surgery for early-stage NPC.MethodsWe retrospectively evaluated 341 patients diagnosed with early-stage NPC between September 2010 and December 2015. Among them, 58 patients underwent endoscopic nasopharyngectomy combined with chemoradiotherapy, whereas 283 patients underwent conventional chemoradiotherapy. The patients who underwent concurrent chemoradiotherapy or radiotherapy alone were matched to patients who underwent surgery in a 1:2 ratio using propensity score matching to analyze the clinical efficacy of each therapeutic modality. The primary endpoint was survival, and the secondary endpoints were tumor regression rate and reduction in Epstein–Barr virus (EBV)-DNA levels.ResultsAfter matching, 156 patients were enrolled (58 patients in the surgery group; 98 patients in the non-surgery group). The baseline data of the matched patients had good inter-group comparability (All P>0.05). The surgery group had significantly higher 5-year overall survival (98.30% vs. 91.70%), disease-free survival (98.30% vs. 81.40%), and recurrence-free survival (100.00% vs. 90.10%) rates than did the non-surgery group (All P<0.05). In total, 0 and 14 patients in the surgery and non-surgery groups, respectively, had residual cancer at the end of treatment (P=0.001). All patients in the surgery group tested negative for EBV-DNA, whereas two patients in the non-surgery group tested positive. The incidence of hematologic toxicity during treatment was similar between the two groups (All P>0.05). Still, the incidence of severe oral mucositis was lower in the surgery group than in the non-surgery group (37.9% vs. 54.08%, P=0.051).ConclusionSurgery can improve the clearance rate of EB virus and reduce tumor residue. Surgery may be a safe and effective treatment for early NPC.

NASOPHARYNGEAL CARCINOMA IN PANYABUNGAN DISTRICT HOSPITAL

Abstract Introduction: Nasopharyngeal carcinoma is the most common malignancy found in the head and neck area. Non-specific initial symptoms and hidden locations often make it difficult to diagnose early nasopharyngeal carcinoma. The limitations of tools and human resources in the district are a problem in enforcing and finding patients with nasopharyngeal carcinoma in this situation. Objective: The purpose of this study is to observe the prevalence of nasopharyngeal carcinoma in Departement of Otorhinolaryngology-Head and Neck Surgery Panyabungan District Hospital. Method: This study collecting data from medical record of Nasopharyngeal carcinoma (NPC) at Panyabungan District Hospital. Result: The distribution of NPC patients during January-December 2018 there were 10 patients. NPC base on gender male 50% and female 50%. NPC based on age groups in 46-55 years is 40%, 56-65 years old is 20% and 16-25 years, 26-35 years, 36-45 years, and 66-75 years each of 10%. NPC patients based of clinical appearance is limadenophaty colli is 100%, epistaxis 80%, Nasal congesty 70%.ear fulness 40% and diplopia 30%. NPC based on histophatologycal types is WHO type I 10%, WHO type II 50% and WHO type III 40%. Conclusion: Nasopharyngeal carcinoma is a malignant tumor originating from the nasopharyngeal epithelium. The patient NPC were diagnosed at an advanced stage. All of patients showed enlargement of neck limph nodes and some showed diplopia.

In silico single polymorphism analysis of RPMS1 and A73 gene in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is one of the most frequent cancer types in Vietnam, with high mortality rate. Therefore, the early diagnosis and detection of NPC is urgently needed to improve patient survival. Recent studies have confirmed that the infection of Epstein-Barr virus (EBV) and polymorphism in RPMS1 and A73 are considered as the etiological factor associated with NPC. However, in Vietnam, there are no studies relevant to the identification of polymorphism of RMPS1 and A73. With the aims, in future, to develop a technique based on detecting the frequencies of RPMS1 and A73 variants as biomarkers of prognosis and early diagnosis of NPC, we conducted the initial in silico analysis (1) Data collection, statistical analysis the frequencies detection of RPMS1 and A73 variants from various previous published studies; (2) Determine experimental methods to predict and diagnose early NPC and examine necessary steps in silico. As the results, we established the systematic databases of RPMS1 and A73 polymorphism, and evaluation the primer set for the amplification of RPMS1 and A73, which could be applied in further studies related to the identification of RPMS1 and A73 gene polymorphism to find out the potential biomarkers for screening, diagnosis as well as NPC treatment.

비인두에 발생한 Melanotic Oncocytic Metaplasia(MOM) 1예

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is a rare lesion that occurs mostly in Asian men in their 60s to 70s who are heavy smokers. Although it is a benign lesion, it’s sometimes mistaken for malignant melanoma, nevus or early nasopharyngeal carcinoma. A 75 year-old male visited our outpatient clinic with hearing loss that occurred a week earlier. Otoscopic findings revealed left serous otitis media. A nasopharyngoscopic examination to rule out a malignant tumor in the nasopharynx revealed multiple black nodules in the left torus tubarius and left nasal floor. Under local anesthesia, some of nodules were excised for histopathology. The histological examination revealed oncocytic metaplasia of mucous glands and the presence of numerous brown-colored melanin pigments. Immunohistochemically, S 100-positive and HMB 45-negative dendritic melanocytes were identified. During 3 months of regular follow up, there was no recurrence at the excision site and no expansion of the remaining lesion. (J Clinical Otolaryngol 2020;31:88-93)

Rac1: A potential radiosensitization target of human nasopharyngeal carcinoma CNE2 cells

Radiotherapy has a high cure rate for early nasopharyngeal carcinoma(NPC). However, the radiation resistance of poorly differentiated NPC cells impacts the effectiveness of treatment of early-stage NPC patients. Here, we explored the relationship between Ras-related C3 botulinum toxin substrate 1(Rac1) expression and NPC radiosensitivity. In vitro and in vivo studies revealed that upregulation of Rac1, when combined with X-ray treatment, increased growth inhibition and induced remarkable morphological changes and apoptosis in CNE2 cells. Furthermore, rupturing of the cell and nuclear membranes, degeneration of the cristae and significant swelling of the mitochondria were observed, which were consistent with the high apoptotic rate. The Rac1(+) cells exhibited approximately 50% more migration compared with that of the NC and Rac1(-) cells. The overexpression of Rac1 can increase the radiation sensitivity of NPC CNE2 cells, and the mechanism may be closely related to the oxidative damage of mitochondria. Rac1 might be a potential target for radiosensitization in poorly differentiated NPC.

Septin 9 Methylation in Nasopharyngeal Swabs: A Potential Minimally Invasive Biomarker for the Early Detection of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia, and an unfavorable outcome is usually attributed to advanced stage NPC. Current methods for the early diagnosis of NPC have limitations in clinical practice. The aim of this study was to investigate the diagnostic ability of Septin 9 methylation for NPC. A quantitative methylation-sensitive PCR (qMS-PCR) assay was developed to measure the methylation status and levels of Septin 9 in nasopharyngeal tissues and paired swabs from patients with NPC, chronic nasopharyngitis, and healthy donors. Methylated Septin 9 was detected in 92% (23/25) of NPC tissues and 25% (4/16) of nasopharyngitis controls (p < 0.05). High-frequency hypermethylation with decreased mRNA expression of Septin 9 in NPC was also identified. Further, Septin 9 methylation was identified in 90.5% (19/21) of NPC biopsies and 71.4% (15/21) of paired swabs, indicating a good concordance between the two sample types. In addition, methylated Septin 9 was found in 16 (72.7%) nasal swabs from 22 NPC patients, 2 of 19 (10.5%) nasopharyngitis, but not in any of the healthy controls (p < 0.01). The methylation score in nasal swabs of the NPC group was also significantly higher than that of non-NPC controls (p < 0.001). Moreover, receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.882 of Septin 9 methylation tests to discriminate NPC from non-NPC subjects. Our study demonstrated that frequent methylation of Septin 9 was present in NPC. Its detection in nasopharyngeal swabs may provide a minimally invasive and informative method for identifying early NPC cases.

Efficacy of Chemiluminescence Immunoassays on VCA-IgA and EBNA1-IgA Antibodies of Epstein-Barr Virus in Diagnosing Nasopharyngeal Carcinoma.

Background: IgA antibodies against Epstein-Barr virus (EBV) capsid antigen (VCA) and nuclear antigen 1 (EBNA1) have been proposed to facilitate the diagnosis and early detection of nasopharyngeal carcinoma (NPC) in high-incidence regions. However, while new methodologies and new platforms for the detection of VCA-IgA and EBNA1-IgA have become available, proper interassay simultaneous comparisons have not been carried out. The study was to compare the performance of the chemiluminescent immunoassays (CLIA) and enzyme-linked immunosorbent assay (ELISA) for VCA-IgA and EBNA1-IgA antibodies, and to evaluate the levels of EBV antibodies in healthy population from different areas of China.Methods: CLIA and ELISA for VCA-IgA and EBNA1-IgA were performed in NPC and healthy populations from high-incidence areas of NPC in South China (N=555), medium-incidence areas of NPC in Central China (N=318) and low-incidence areas of NPC in North China (N=379), and the results were compared and analyzed.Results: (1) The highest sensitivity in total, early and advanced NPC were 91.5% (CLIA for VCA-IgA), 86.4% (CLIA and ELISA-2 for EBNA1-IgA) and 93.6% (CLIA for VCA-IgA). However, the specificity of EBV-IgA measured by CLIA was relatively lower than ELISA. The top three seromarkers with the largest AUC was CLIA for VCA-IgA (AUC: 0.929, 95% CI: 0.905-0.953), ELISA-2 for EBNA1-IgA (AUC: 0.922, 95% CI: 0.896-0.947) and CLIA for EBNA1-IgA (AUC:0.919, 95% CI: 0.893-0.945), respectively. The positive and negative coincidence rates of the two EBNA1-IgA kits were 69.5% and 91.9%, respectively. However, the coincidence rates of VCA-IgA were relatively low. CLIA kits had good repeatability between different laboratories. (2) The positive rates of EBV-IgA antibodies were relatively high in high-incidence areas of NPC (P < 0.017), while there was no significant difference in the antibody positive rates between medium-incidence areas and low-incidence areas of NPC (P > 0.05).Conclusions: The performance of EBV-IgA antibodies measured by CLIA has good repeatability, higher sensitivity and similar specificity. The higher EBV-IgA positive rate in healthy subjects by CLIA raises concern about its suitability for NPC-risk screening and requires further analysis.

Overall assessment of tumour-infiltrating lymphocytes in early-stage nasopharyngeal carcinoma

Abstract Background Nasopharyngeal carcinoma (NPC) has distinct histopathology and associated with high mortality rate. Identification of NPC cases that have aggressive behavior at an early-stage can aid in improvement of the survival. Assessment of tumor-infiltrating lymphocytes (TILs) has shown a promising prognostic value in many epithelial cancers. Methods This study included a multicenter cohort of 44 cases treated for early-stage (I-II) NPC at the five Finnish university hospitals (Helsinki, Turku, Tampere, Kuopio and Oulu). Hematoxylin and eosin-stained cancer sections were used to evaluate TILs. We followed the guidelines that recently introduced by International Immuno-Oncology Biomarkers Working Group for assessment of TILs in different tumors including head and neck cancer. Results The score of intra-tumoral TILs showed a promising prognostic value for predicting survival in early NPC. A hazard ratio of 2.45 and 95% confidence interval of 1.07 to 5.62 (P = 0.03) was reported, indicates that tumors with low TILs have a higher risk of mortality. Conclusion In early-stage of NPC, assessment of TILs has a significant prognostic value that can be useful to identify cases with aggressive behavior. Further studies are necessary to validate the importance of TILs in larger cohorts of early NPC. Legal entity responsible for the study Alhadi Almangush. Funding Has not received any funding. Disclosure The author has declared no conflicts of interest.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. Among 70296 total subjects, 29413 screened participants (41.8% of the total subjects) in the screening group and 50636 in the control group, 153 (43.3 per 100000 person-year), 62 (55.3 per 100000 person-year) and 99 (33.1 per 100000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. NCT00941538.