Diagnosis Of Nasopharyngeal Carcinoma Research Articles

Diagnostic and Prognostic Potential of Circulating and Tissue BATF2 in Nasopharyngeal Carcinoma.

Background: Current biomarkers for nasopharyngeal carcinoma (NPC) are less effective for early diagnosis and prognosis. The basic leucine zipper ATF-like transcription factor 2 (BATF2) gene has been shown to have a tight association with the pathogenesis of various malignancies but received scant attention in NPC research. We aimed to assess the performances of circulating and tissue BATF2 in the diagnosis and prognosis of NPC. Materials and Methods: Immunohistochemistry (IHC) microarrays were performed to quantitate the BATF2 protein expression in NPC tissues. The relationships of BATF2 protein expression with clinicopathological characteristics and NPC prognosis were assessed. BATF2 mRNA expressions in serum and serum-derived exosomes were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. Results: The IHC microarrays revealed a predominant nuclear expression of BATF2 in NPC cells. The Kaplan-Meier survival analysis showed that BATF2-positive NPC patients enjoyed longer overall survival than BATF2-negative patients. NPC patients with serum and exosomal BATF2 mRNA expressions made up 51.47 and 48.52% of all patients, respectively. The AUCs of serum and exosomal BATF2 mRNA expressions in discriminating NPC from healthy controls were 0.9409 and 0.8983. Patients who had received radiochemotherapy exhibited higher serum and exosomal BATF2 mRNA expressions versus the levels at baseline as well as those detected in recurrent patients. Conclusion: BATF2 is expressed cancerous tissues, serum, and serum-derived exosomes in NPC patients. Circulating and tissue BATF2 can serve as a multipurpose biomarker capable of the diagnosis, prognosis prediction, efficacy evaluation, and recurrence monitoring in NPC.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.

Cranial Neuropathies in Advanced Nasopharyngeal Carcinoma: Neurological Recovery and Prognosis After Modern Radiotherapy and Systemic Chemotherapy

Cranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. This study sets to evaluate the prognostic factors and recovery pattern of cranial neuropathies, using longitudinal clinical data from two tertiary oncology centers in endemic areas.Case records of consecutive T4 NPC patients who received definitive IMRT in 2004-2019 were reviewed. Distribution of cranial neuropathies at disease presentation were recorded. Time to partial and full neurological recovery, time from neurological recovery to re-palsy, relapse-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors for neurological recovery were analyzed using multivariable Cox regression.During the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was 2 months (IQR, 1-4 months). All patients completed definitive IMRT, and 94% of patients received chemotherapy. The 5-year RFS and OS of the combined cohort were 50.8% and 60.1% respectively. Median RFS of patients with single versus multiple neuropathies were 5.8 years and 4.2 years (P = 0.62). Cranial nerves (CN) VI (56.4%), V2 (47.9%) and V3 (29.2%) were most frequently involved. Over a median follow-up of 6.4 years, 111 (22%) and 289 (57.3%) neuropathies attained partial and full recovery respectively, and 86% of the recoveries occurred within the first year after definitive radiotherapy. CN III, IV, VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), CN XII (48.6%), and CN II (18.2%) (P < 0.001). Positive smoking history, optic nerve involvement, and long duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences at the base of skull.Rate and durability of cranial neuropathy recovery in this contemporary NPC cohort compared favorably with data from the 2D radiotherapy era. Both patient and disease factors affected the chance of nerve recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.

Silencing of NACC1 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via regulating the AKT/mTOR signaling pathway.

Nucleus accumbens-associated protein 1 (NACC1) has been reported to serve as an oncogenic role in several types of cancer; however, its role in nasopharyngeal carcinoma (NPC) remains to be determined. The present study aimed to investigate the role of NACC1 in NPC and elucidate the underlying mechanisms. Therefore, NACC1 expression in the normal nasopharyngeal epithelial cell line, NP69, and various NPC cell lines was determined by reverse transcription-quantitative PCR and western blot analyses. NACC1 expression was silenced in the NPC SUNE-1 cell line by transfection with a short hairpin RNA. Cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were then evaluated using MTT, colony formation, wound healing, Transwell and western blot assays, respectively. SC79 was employed to activate AKT expression in NACC1-silenced SUNE-1 cells, and the aforementioned cellular processes were observed. The results revealed that NACC1 expression was upregulated in NPC cell lines. NACC1-knocdown inhibited SUNE-1 cell proliferation, migration, invasion and EMT. Moreover, the levels of phosphorylated AKT and mTOR were decreased upon NACC1 silencing. Mechanistically, the presence of SC79 significantly blocked all the effects of NACC1-knockdown on SUNE-1 cells. The findings of the present study demonstrated that NACC1-knockdown effectively suppressed NPC cell proliferation, migration and invasion by inhibiting the activation of the AKT/mTOR signaling pathway. NACC1 may thus serve as a potential target for the diagnosis and therapy of NPC.

Pathological and genomic phenotype of second neuroendocrine carcinoma during long-term follow-up after radical radiotherapy for nasopharyngeal carcinoma

BackgroundSecond head and neck neuroendocrine carcinoma (NEC) after radical radiotherapy for nasopharyngeal carcinoma (NPC) treatment is rarely reported. The prognosis of second cancer is poor, and our research focuses on finding a breakthrough in the treatment. In this study, we aimed to investigate clinicopathological characteristics and to identify the genomic landscape of second head and neck NECs.MethodsWe collected five second head and neck NEC cases in the recent three years from our patient database. Clinicopathological data and images were obtained. Genomic analysis was performed using high-throughput second generation sequencing. KEGG pathway enrichment analyses between high-frequency mutations were performed using the STRING database.ResultsAll patients had been diagnosed with second NEC, according to the pathological observations. The interval between diagnosis of NPC and NEC ranged from 10 to 18 years. Two patients had brain or liver metastasis at three and nine months, respectively, after the diagnosis of NEC. Three patients died of the disease with the overall survival time ranging from three to nine months. Commonly altered genes (50%) in second head and neck NECs included TP53, RB1, NOTCH2, PTEN, POLG, KMT2C, U2AF1, EPPK1, ELAC2, DAXX, COL22A1, and ABL1. Those genetic lesions might affect p53 signaling, MAPK signaling, PI3K-Akt signaling, sphingolipid signaling, and neurotrophin signaling pathways.ConclusionsSecond head and neck NECs had poor prognosis. We revealed, for the first time, the mutational landscape, high-frequency somatic mutations, and potential signaling pathways of second head and neck NECs. Its optimal treatment model needs to be further studied in future clinical trials.

Tumor-Educated Platelet miR-18a-3p as a Novel Liquid-Biopsy Biomarker for Early Diagnosis and Chemotherapy Efficacy Monitoring in Nasopharyngeal Carcinoma.

AimsTo evaluate the value of tumor-educated platelet (TEP) miR-18a-3p in the early diagnosis and chemotherapy efficacy monitoring of nasopharyngeal carcinoma (NPC).MethodsExpression levels of miR-18a-3p in platelets and plasma were detected by relative quantitative real-time PCR in NPC patients (n=54) and normal subjects (n=36). Diagnostic values of TEP miR-18a-3p for NPC was assessed by receiver operating characteristic (ROC) curve analysis. Follow up study was carried out to observe the dynamic changes of TEP miR-18a-3p with chemotherapy on 3 NPC patients.ResultsThe expression levels of TEP miR-18a-3p in NPC patients were significantly higher than that in healthy controls (p < 0.0001). ROC curve analysis showed that the area under the curve (AUC) value was 0.841, the sensitivity and specificity for the diagnosis of NPC were 87% and 72.7%. No correlation was found between expression levels of TEP miR-18a-3p and patients’ clinical parameters and their NPC tumor-node-metastasis (TNM) stage. The positive rate of TEP miR-18a-3p and EBV DNA for NPC diagnosis were 85.4% and 66.7%. TEP miR-18a-3p expression were down-regulated after 77.8% (7 of 9) of chemotherapy, and in 66.7% (2 of 3) patients, TEP miR-18a-3p levels decreased after 3 cycles of chemotherapy.ConclusionThe expression levels of TEP miR-18a-3p are upregulated in NPC and have a high probability to downregulated after chemotherapy, indicating a significant clinical value. TEP miR-18a-3p might serve as a novel type of liquid-biopsy biomarker for early diagnosis and chemotherapy efficacy monitoring in NPC.

PUSHING THE ENVELOPE WITH POLYGENIC RISK SCORES IN PSYCHIATRIC GENETICS: WHETHER, WHEN, AND HOW TO IMPLEMENT

Nasopharyngeal carcinoma (NPC) is considered a rare malignant head and neck tumour. However, the importance of genetics and environmental factors in the epidemiology of NPC is still unclear. Twins represent an excellent study population for genetic epidemiology; this is especially true of monozygotic-type twins because they are genetically identical. The difference in cancer occurrence between monozygotic twins is typically interpreted as a result of possible environmental factors.We present the first case report of monozygotic twins with NPC. The twins' significant features are homogenous presentation, tumour location (both left-sided) and identical histology; therefore, the prognoses may be similar. Environmental factors could not be addressed in these twins because they shared the same background, and at the same time, they had no potential known contributing factors.Having one of the twins affected is a strong and easily recognisable risk factor for developing NPC in the other. This strong association suggests the need for regular screening of the second twin for early diagnosis of NPC.

Novel EBV LMP1 C-terminal domain binding affibody molecules as potential agents for in vivo molecular imaging diagnosis of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) latent infection and is common in Southern China and Southeast Asia. The viral latent membrane proteins LMP1 and LMP2 are persistently expressed in NPC tissues; the cytoplasmic domain of LMP1 (LMP1 C-terminal) and LMP2A (LMP2A N-terminal) proteins is essential for maintenance of latency and can alter host cell signaling to facilitate tumor growth and progression. Thus, targeting LMP1 or LMP2 oncoprotein has been an increasing interest for diagnosis and targeted therapy of NPC. Affibody molecules, a new class of small-affinity engineered scaffold proteins, have demonstrated high potential for therapeutics, diagnostics, and biotechnological applications. More recently, radiolabelled HER2-specific affibody molecules have demonstrated to be useful in imaging of HER2 expressing tumor. In this study, we report three novel EBV LMP1 C-terminal (EBV LMP1-C) domain affibody molecules (ZLMP1-C15, ZLMP1-C114, and ZLMP1-C277) were selected by biopanning from a random-peptide displayed phage library and used for molecular imaging in tumor-bearing nude mice. Surface plasmon resonance (SPR), indirect immunofluorescence, and immunohistochemistry (IHC) clearly showed that all three selected affibody molecules have high affinity and specificity in binding to EBV LMP1 protein. Moreover, in vivo tumor imaging revealed that Dylight-755-labeled affibody molecules accumulated rapidly in tumor site after injection (1h) and then were continuously maintained for 24h in EBV-positive NPC xenograft mice model. In conclusion, our findings highlight the potential use of ZLMP1-C affibody molecules as tumor-specific molecular imaging agents of EBV-associated NPC.Key points• We screened three novel affibody molecules (ZLMP1-C15, ZLMP1-C114, and ZLMP1-C277) targeting EBV LMP1-C terminal domain• ZLMP1-C recognize the recombinant and native LMP1-C with high affinity and specificity• ZLMP1-C can be used for molecular imaging.

Cranial neuropathies in advanced nasopharyngeal carcinoma: Neurological recovery after modern radiotherapy and systemic chemotherapy

ObjectivesCranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. Materials and methodsCase records of consecutive T4 NPC patients who received definitive IMRT in two tertiary oncology centers in 2004–2019 were reviewed. Patterns of cranial neuropathies at disease presentation were recorded. Time to neurological recovery and the rate of subsequent re-palsy were estimated by the Kaplan-Meier method. Clinical predictors were analyzed using multivariable Cox regression. ResultsDuring the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was two months (IQR, 1–4 months). Cranial nerves (CN) VI (56.4%), V2 (47.9%), and V3 (29.2%) were most frequently involved. At a median follow-up of 6.4 years, the crude partial and full recovery rates of neuropathies were 111 (22%) and 289 (57.3%), respectively. CN III, IV, and VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), XII (48.6%), and II (18.2%) (p < 0.001). Positive smoking history, optic nerve involvement, and longer duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences. ConclusionDurable recovery of most cranial neuropathies in advanced T4 NPC was observed in the era of modern IMRT and effective systemic chemotherapy. Both patient and disease factors affected the chance of neurological recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.

883P Preliminary study of a new antibody marker anti-EBV BNLF2b in screening population in high-incidence areas of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is common in southern China. Despite being widely utilized, the positive predictive value (PPV) of the NPC screening scheme of China Ministry of Health based on two EBV IgA is still low. We have newly discovered a new type of anti-EBV antibody (BNLF2b-Ab), which significantly improved specificity in diagnosis of NPC, but its application value in population screening is still unclear.

A comprehensive risk score for effective risk stratification and screening of nasopharyngeal carcinoma

Using Epstein-Barr virus (EBV)-based markers to screen populations at high risk for nasopharyngeal carcinoma (NPC) is an attractive preventive approach. Here, we develop a comprehensive risk score (CRS) that combines risk effects of EBV and human genetics for NPC risk stratification and validate this CRS within an independent, population-based dataset. Comparing the top decile with the bottom quintile of CRSs, the odds ratio of developing NPC is 21 (95% confidence interval: 12–37) in the validation dataset. When combining the top quintile of CRS with EBV serology tests currently used for NPC screening in southern China, the positive prediction value of screening increases from 4.70% (serology test alone) to 43.24% (CRS plus serology test). By identifying individuals at a monogenic level of NPC risk, this CRS approach provides opportunities for personalized risk prediction and population screening in endemic areas for the early diagnosis and secondary prevention of NPC.

A Comprehensive Review on Radiomics and Deep Learning for Nasopharyngeal Carcinoma Imaging.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck, and improving the efficiency of its diagnosis and treatment strategies is an important goal. With the development of the combination of artificial intelligence (AI) technology and medical imaging in recent years, an increasing number of studies have been conducted on image analysis of NPC using AI tools, especially radiomics and artificial neural network methods. In this review, we present a comprehensive overview of NPC imaging research based on radiomics and deep learning. These studies depict a promising prospect for the diagnosis and treatment of NPC. The deficiencies of the current studies and the potential of radiomics and deep learning for NPC imaging are discussed. We conclude that future research should establish a large-scale labelled dataset of NPC images and that studies focused on screening for NPC using AI are necessary.

Convolutional Neural Network Intelligent Segmentation Algorithm-Based Magnetic Resonance Imaging in Diagnosis of Nasopharyngeal Carcinoma Foci.

The aim of this study was to explore the adoption value of convolutional neural network- (CNN-) based magnetic resonance imaging (MRI) image intelligent segmentation model in the identification of nasopharyngeal carcinoma (NPC) lesions. The multisequence cross convolutional (MSCC) method was used in the complex convolutional network algorithm to establish the intelligent segmentation model two-dimensional (2D) ResUNet for the MRI image of the NPC lesion. Moreover, a multisequence multidimensional fusion segmentation model (MSCC-MDF) was further established. With 45 patients with NPC as the research objects, the Dice coefficient, Hausdorff distance (HD), and percentage of area difference (PAD) were calculated to evaluate the segmentation effect of MRI lesions. The results showed that the 2D-ResUNet model processed by MSCC had the largest Dice coefficient of 0.792 ± 0.045 for segmenting the tumor lesions of NPC, and it also had the smallest HD and PAD, which were 5.94 ± 0.41 mm and 15.96 ± 1.232%, respectively. When batch size = 5, the convergence curve was relatively gentle, and the convergence speed was the best. The largest Dice coefficient of MSCC-MDF model segmenting NPC tumor lesions was 0.896 ± 0.09, and its HD and PAD were the smallest, which were 5.07 ± 0.54 mm and 14.41 ± 1.33%, respectively. Its Dice coefficient was lower than other algorithms (P < 0.05), but HD and PAD were significantly higher than other algorithms (P < 0.05). To sum up, the MSCC-MDF model significantly improved the segmentation performance of MRI lesions in NPC patients, which provided a reference for the diagnosis of NPC.

Promoter Hypermethylation of Tumor Suppressor Genes Located on Short Arm of the Chromosome 3 as Potential Biomarker for the Diagnosis of Nasopharyngeal Carcinoma.

DNA methylation, the most common epigenetic alteration, has been proven to play important roles in nasopharyngeal carcinoma (NPC). Numerous tumor suppressor genes located on the chromosome 3p, particularly in the region of 3p21, are frequently methylated in NPC, thus suggesting great potential for diagnosis of NPC. In this review, we summarize recent findings of tumor suppressor genes on chromosome 3 that likely drive nasopharyngeal tumor development and progression, based on previous studies related to the hypermethylation of these target genes. Better understanding will allow us to design further experiments to establish a potential test for diagnosis of NPC, as well as bring about methylated therapies to improve the treatment of NPC.

The Efficacy of Radiotherapy for Nasopharyngeal Carcinoma under Magnetic Resonance Imaging

This study aimed to analyze the application value of diffusion tensor imaging (DTI) in the diagnosis of nasopharyngeal carcinoma (NC) radiotherapy. In this study, 102 patients with NC were selected as the experimental group (EG), and 58 healthy people examined in hospital were included in a control group (CG). All subjects were required to be examined with routine magnetic resonance imaging (MRI) and DTI before and after the treatment. The fractional anisotropy (FA) of the patients in EG before and after treatment and the CG were recorded. The apparent diffusion coefficients (ADC) of patients in the two groups were measured and recorded before and after the treatment. The recovery rate and adverse events of the patients in EG were observed and recorded after the treatment. The results showed that the FA values of the right cerebellum and left parietal lobe (LPL) of patients after treatment in the EG were much higher than those before treatment and the CG (P < 0.05); the FA values of the right temporal lobe (RTL), right occipital lobe (ROL), and right parietal lobe (RPL) after treatment in the EG were obviously lower than those before the treatment and the CG (P < 0.05); the complete remission rate (CRR) of the EG after treatment was greatly higher than the partial remission rate (PRR) and disease stability rate (DSR) (P < 0.05), and the objective remission rate (ORR) and disease control rate (DCR) were higher than 90%, respectively. The ADC value of the EG before treatment was (0.752 ± 0.021) × 10−3 mm2/s, which was visibly lower than that after treatment ((1.365 ± 0.058) × 10−3 mm2/s) and that in the CG ((1.856 ± 0.079)) × 10−3 mm2/s), showing statistically obvious differences (P < 0.05). The incidence of anemia, oral reactions, hypertension, and gastrointestinal reaction in the EG after treatment was 61.46%, 45.35%, 47.28%, and 39.67%, respectively. In short, the FA value of DTI parameter could clearly indicate the changes in brain area characteristics of NC patients before and after treatment. The RTL, ROL, and RPL of NC patients were damaged after radiotherapy, and the FA value decreased observably, which may be related to brain edema and demyelination changes. The damage of white matter microstructure in each brain area further affected the cognitive function of the patient.

Upregulation of miRNA-155 in Nasopharyngeal Carcinoma Patients.

Background:The upregulation of miRNA-155 (miR-155) has been associated with oncogenesis of many human tumors, including nasopharyngeal carcinoma (NPC). However, the profile of miR-155 in Vietnamese NPC patients has not been investigated. The current study aimed to evaluate the miR-155 expression and assess whether miR-155 is a potential biomarker for diagnosis of NPC in Vietnamese patients.Methods:In current case-control study, total of RNA was isolated from 60 biopsy NPC samples and 60 non-cancerous swab samples were analyzed by Reverse-transcription PCR, qualitative Real-time PCR.Results:The frequency of miR-155 detection were 78.33%, 15.0% in NPC and non-cancerous samples (P<0.05), respectively. The miR-155 expression level was 4.92 times higher in tumor samples than non-cancerous sample.Conclusion:Taken together, miR-155 in NPC was upregulated. It may serve as a potential biomarker for NPC in the Vietnamese population.

Simultaneously Both Expression of LMP-1 and Methylation of E-cadherin: Molecular Biomarker in Stage IV of Nasopharyngeal Carcinoma Patients.

The phenome of E-cadherin gene methylation and the expression of latent membrane protein 1 (LMP-1) gene are associated with nasopharyngeal carcinoma (NPC). In order to determine whether cooperative LMP-1 expression or methylation of E-cadherin could serve as the potential molecule biomarker target for diagnosis and therapy of NPC, a case-control study including 93 NPC biopsy samples and 100 non cancerous nasopharyngeal swab samples were examined, as well as the strength of association among them by the quantitative polymerase chain reaction (qPCR) and nested-methylation-specific PCR methods. The significantly higher frequency of LMP-1 expression and E-cadherin methylation in NPC biopsy samples, accounting for 76.34 and 73.12%, respectively, compared to non cancerous samples, accounting for 0.00 and 30.00%, respectively, were observed. The significant correlation between the LMP-1 expression and E-cadherin methylation in NPC samples was reported. In detail, in the stage IV of NPC, in case of LMP-1-positive samples, 35 of 37 samples (accounting for 94.60%) were positive for methylation of E-cadherin. It was demonstrated that cooperative LMP-1 expression and E-cadherin gene methylation could serve as a molecular biomarker in NPC.

Performance of Plasma HSP90α, Serum EBV VCA IgA Antibody and Plasma EBV DNA for the Diagnosis and Prognosis Prediction of Nasopharyngeal Carcinoma.

ObjectiveThe aim of this study was to evaluate the effectiveness of Epstein–Barr virus (EBV) VCA-IgA antibody, EBV DNA and HSP90α alone or in combinations for the diagnosis and prognostic prediction of nasopharyngeal carcinoma (NPC).MethodsA total of 113 treatment-naïve patients with NPC and 40 healthy controls were enrolled. Plasma HSP90α and serum EBV VCA IgA antibody were detected using ELISA, and plasma EBV DNA was quantified using qPCR assay. The effectiveness of plasma HSP90α level, serum EBV VCA IgA antibody and plasma EBV DNA was examined in the diagnosis and prognosis prediction of NPC.ResultsHigher plasma HSP90α, serum EBV VCA IgA antibody and plasma viral load of EBV DNA were detected in NPC patients than in healthy controls (P < 0.001). The plasma HSP90α levels, serum EBV VCA IgA antibody titers and plasma viral load of EBV DNA were significantly greater in NPC patients with stages III and IV than in those with stages I and II (P < 0.001), and significantly lower plasma HSP90α levels, serum EBV VCA IgA antibody titers and plasma viral load of EBV DNA were found in the good prognosis group than in the poor prognosis group post-treatment (P < 0.05). The area under representative operating curves (AUCs) of plasma HSP90α, serum EBV VCA IgA antibody and plasma EBV DNA alone and in combination were 0.884, 0.841, 0.934 and 0.954 for the diagnosis of NPC, respectively. Univariate and multivariate Cox proportional hazards regression analyses identified HSP90α as an independent prognostic factor for NPC.ConclusionThe combination of plasma HSP90α, serum EBV VCA IgA antibody and plasma EBV DNA shows high diagnostic performance for NPC, and plasma HSP90α may be a potential marker for diagnosis and prognosis prediction of NPC.

S100A8/A9 Molecular Complexes Promote Cancer Migration and Invasion via the p38 MAPK Pathway in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is one type of malignancy associated with migration and invasion through a currently unclear mechanism. We previously discovered S100A8/A9 levels were roughly elevated in the plasma of NPC patients as the promising biomarkers. However, their expressions and underlying functions in NPC tissues are still unknown. In the present study, we analyzed 49 NPC tissues and 20 chronic pharyngitis (CP) tissues. Immunohistochemical staining was performed in different tissues and analyzed by the Mann–Whitney U test statistically. Transwell migration and invasion experiments were further performed to determine S100A8/A9 effects on NPC. Our results showed that S100A8/A9 in NPC tissues were significantly higher than those in CP tissues, closely associated with NPC clinical stages. Intriguingly, exogenous S100A8/A9 protein stimulation could dramatically enhance NPC migration and invasion abilities. In addition, p38 MAPK pathway blockade could diminish the migration and invasion of NPC cells stimulated by S100A8/A9 proteins. The downstream tumor invasion and migration associated proteins (e.g., MMP7) were also elevated in NPC tissues, consistent with S100A8/A9 overexpression. Taken together, our present findings suggest that the secreted soluble inflammatory factors S100A8/A9 might promote cancer migration and invasion via the p38 MAPK signaling pathway along with invasion/migration associated proteins overexpression in the tumor microenvironment of NPC. This may shed light on the mechanism understanding of NPC prognosis and provide more novel clues for NPC diagnosis and therapy.

The Contrast-Enhanced MRI Could Be Substituted by Unenhanced MRI in the Differential Diagnosis of Nasopharyngeal Carcinoma But Not in Segmentation with the Aid of Deep Learning Models : An Exploratory Study in Large-Scale Population of Endemic Area

Background: No consensus in sequence selection for artificial intelligence model development has been achieved, we aimed to explore whether contrast-enhanced magnetic resonance imaging (ceMRI) could be substituted in the identification and segmentation of nasopharyngeal carcinoma (NPC) with the aid of deep learning models in a large-scale cohort. Methods: A total of 4,478 eligible individuals were randomly split into training, validation and test sets. The diagnostic performance between NPC and benign hyperplasia and segmentation efficacy in NPC were compared among self-constrained 3D DenseNet models developed using axial T1-weighted imaging (T1WI), T2WI or enhanced T1WI (T1WIC) images separately. Findings: All developed models exhibited similar satisfactory diagnostic performance in discriminating NPC from benign hyperplasia, attaining over accuracy over 99.00% in all T stages of NPC. However, the T1WIC model yielded a significantly higher dice similarity coefficient (DSC) and lower average surface distance (ASD) than either the T1WI model or T2WI model in the test set of NPC cohort (DSC, 0.768±0.070 vs 0.759±0.065 and 0.755±0.071, p < 0.001; ASD, 1.573±0.954 mm vs 1.661±0.898 mm and 1.722±1.133 mm, p < 0.01).Interpretation: Unenhanced MRI could substitute ceMRI in discriminating NPC from benign hyperplasia but not in the segmentation for NPC with the aid of deep learning models and ceMRI remained the optimal sequence for developing segmentation models for NPC , indicating the feasibility of reducing the use of MR contrast in screening program. Funding: This work was supported by the National Natural Science Foundation of China [Grant No. 31900461, 81702873, 81872375, 81572665, 81802712]. Declaration of Interest: Nothing to disclose. Ethical Approval: The ethics committee of the authors’ institution approved the study protocol and patient consent was waived due to the retrospective nature of the study.