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1.
Zhonghua Nei Ke Za Zhi ; 63(5): 490-494, 2024 May 01.
Article in Chinese | MEDLINE | ID: mdl-38715487

ABSTRACT

The study presents an analysis of the diagnostic and treatment protocol for a patient with a first episode of nasopharyngeal carcinoma who also has Sjogren's syndrome and Epstein-Barr Virus (EBV) positive cerebrospinal fluid, as detected through metagenomic next-generation sequencing (mNGS). It reviews existing literature to examine the connections between EBV and various conditions including Sjogren's syndrome, encephalitis or meningitis, and nasopharyngeal carcinoma, emphasizing the importance of EBV positive cerebrospinal fluid. The study focuses on a case from the Eighth Medical Center of the General Hospital of the People's Liberation Army, where a patient was admitted with headaches as the primary symptom on March 3, 2021. This patient had a history of Sjogren's syndrome and was later diagnosed with nasopharyngeal carcinoma. The research involved reviewing both domestic and international databases for cases related to cerebrospinal fluid EBV positive encephalitis or meningitis, and nasopharyngeal carcinoma. It aimed to aggregate data on demographics, initial symptoms, treatment methods, and patient outcomes. Findings suggest that positive cerebrospinal fluid EBV is linked to autoimmune diseases, viral encephalitis or meningitis, and nasopharyngeal carcinoma, albeit infrequently in the context of Sjogren's syndrome. Notably, EBV positive cerebrospinal fluid is commonly associated with recurrent nasopharyngeal carcinoma rather than initial episodes. The study concludes that for patients with an immune condition, exhibiting symptoms like headaches or cranial nerve issues, or in cases where nasopharyngeal carcinoma is suspected, early testing through cerebrospinal fluid mNGS or EBV DNA is recommended. This approach facilitates risk assessment, prognosis determination, and the creation of individualized treatment plans.


Subject(s)
Herpesvirus 4, Human , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Sjogren's Syndrome , Humans , Sjogren's Syndrome/cerebrospinal fluid , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/complications , Sjogren's Syndrome/virology , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/cerebrospinal fluid , Herpesvirus 4, Human/isolation & purification , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/cerebrospinal fluid , Epstein-Barr Virus Infections/cerebrospinal fluid , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/complications , High-Throughput Nucleotide Sequencing
2.
Front Immunol ; 15: 1375931, 2024.
Article in English | MEDLINE | ID: mdl-38736892

ABSTRACT

Objective: This study aimed to establish an effective prognostic model based on triglyceride and inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), to predict overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Additionally, we aimed to explore the interaction and mediation between these biomarkers in their association with OS. Methods: A retrospective review was conducted on 259 NPC patients who had blood lipid markers, including triglyceride and total cholesterol, as well as parameters of peripheral blood cells measured before treatment. These patients were followed up for over 5 years, and randomly divided into a training set (n=155) and a validation set (n=104). The triglyceride-inflammation (TI) score was developed using the random survival forest (RSF) algorithm. Subsequently, a nomogram was created. The performance of the prognostic model was measured by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The interaction and mediation between the biomarkers were further analyzed. Bioinformatics analysis based on the GEO dataset was used to investigate the association between triglyceride metabolism and immune cell infiltration. Results: The C-index of the TI score was 0.806 in the training set, 0.759 in the validation set, and 0.808 in the entire set. The area under the curve of time-dependent ROC of TI score in predicting survival at 1, 3, and 5 years were 0.741, 0.847, and 0.871 respectively in the training set, and 0.811, 0.837, and 0.758 in the validation set, then 0.771, 0.848, and 0.862 in the entire set, suggesting that TI score had excellent performance in predicting OS in NPC patients. Patients with stage T1-T2 or M0 had significantly lower TI scores, NLR, and PLR, and higher LMR compared to those with stage T3-T3 or M1, respectively. The nomogram, which integrated age, sex, clinical stage, and TI score, demonstrated good clinical usefulness and predictive ability, as evaluated by the DCA. Significant interactions were found between triglyceride and NLR and platelet, but triglyceride did not exhibit any medicating effects in the inflammatory markers. Additionally, NPC tissues with active triglyceride synthesis exhibited high immune cell infiltration. Conclusion: The TI score based on RSF represents a potential prognostic factor for NPC patients, offering convenience and economic advantages. The interaction between triglyceride and NLR may be attributed to the effect of triglyceride metabolism on immune response.


Subject(s)
Nasopharyngeal Carcinoma , Nomograms , Triglycerides , Humans , Male , Female , Retrospective Studies , Triglycerides/blood , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/blood , Middle Aged , Prognosis , Adult , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/immunology , Nasopharyngeal Neoplasms/blood , Inflammation/immunology , Inflammation/blood , Aged , Biomarkers, Tumor/blood , ROC Curve , Neutrophils/immunology , Neutrophils/metabolism , Blood Platelets/metabolism , Blood Platelets/immunology , Lymphocytes/immunology , Lymphocytes/metabolism
3.
Exp Clin Transplant ; 22(4): 307-310, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38742322

ABSTRACT

Posttransplant lymphoproliferative disorder is a life-threatening complication after solid-organ transplants. In adults, recipients of heart transplants have the highest risk, whereas renal transplant recipients have the lowest risk among all solid-organ transplants. The most common site for posttransplant lymphoproliferative disorders are gastrointestinal tract followed by the graft itself. Airway involvement in posttransplant lymphoproliferative disorder is rarely encountered. We report a case of a 26-year-old renal allograft recipient who presented to the emergency room with airway obstruction necessitating an emergency tracheostomy. Imaging revealed a left tonsillar mass extending into the nasopharynx and retropharyngeal space causing complete oropharyngeal occlusion. Endoscopic biopsy from nasopharyngeal mass showed a diffuse large B-cell lymphoma and was Ebstein-Barr virus positive. Reduction in immunosuppression and treatment with posttransplant lymphoproliferative disorder-1 risk-stratified approach resulted in complete remission.


Subject(s)
Airway Obstruction , Immunosuppressive Agents , Kidney Transplantation , Lymphoma, Large B-Cell, Diffuse , Humans , Kidney Transplantation/adverse effects , Adult , Treatment Outcome , Airway Obstruction/etiology , Airway Obstruction/virology , Airway Obstruction/diagnosis , Immunosuppressive Agents/adverse effects , Male , Lymphoma, Large B-Cell, Diffuse/virology , Acute Disease , Biopsy , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/immunology , Tracheostomy/adverse effects , Remission Induction , Immunocompromised Host , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/surgery , Nasopharyngeal Neoplasms/diagnosis
4.
Cancer Med ; 13(7): e7144, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38545735

ABSTRACT

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Early Detection of Cancer , Nasopharyngeal Neoplasms , Adult , Humans , Nasopharyngeal Carcinoma/diagnosis , Machine Learning , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/epidemiology , Delivery of Health Care
5.
Sci Rep ; 14(1): 7433, 2024 03 28.
Article in English | MEDLINE | ID: mdl-38548853

ABSTRACT

Epstein-Barr virus (EBV) encoded microRNA BART8-3p (miR-BART8-3p) was significantly associated with the metastasis in nasopharyngeal carcinoma (NPC). To explore the clinical values of plasma miR-BART8-3p in patients with early NPC. We retrospectively analyzed 126 patients with stage I and II NPC. A receiver operating characteristic curve was used to examine the diagnostic performance. Kaplan‒Meier analysis was applied to determine survival differences. Cox regression was used for univariate and multivariate analyses. Compared to healthy subjects, plasma EBV miR-BART8-3p was highly expressed in early NPC patients. The sensitivity, specificity, and area under the curve value of plasma miR-BART8-3p combined with plasma EBV DNA was up to 88.9%, 94.4%, and 0.931. Compared to patients with low expression of miR-BART8-3p, patients with high expression of miR-BART8-3p had poorer 5-year overall survival (OS) (98.9% vs. 91.1%, P = 0.025), locoregional recurrence-free survival (LRRFS) (100% vs. 83.9%, P < 0.001) and distant metastasis-free survival (DMFS) (98.9% vs. 88.0%, P = 0.006). Risk stratification analysis revealed that high-risk patients (with high levels of EBV DNA and miR-BART8-3p) had inferior OS, LRRFS, and DMFS than low-risk patients (without high levels of EBV DNA and miR-BART8-3p). Multivariate analysis verified that the high-risk group was an unfavorable factor for OS, LRRFS, and DMFS. A combination of plasma EBV miR-BART8-3p and EBV DNA could be a potential biomarker for the diagnosis and prognosis in early NPC.


Subject(s)
Epstein-Barr Virus Infections , MicroRNAs , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Prognosis , Epstein-Barr Virus Infections/pathology , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , Retrospective Studies , Biomarkers/metabolism , DNA, Viral/metabolism
6.
PLoS One ; 19(3): e0300067, 2024.
Article in English | MEDLINE | ID: mdl-38527072

ABSTRACT

INTRODUCTION: There is currently no gold standard or specific nutritional assessment tool to assess malnutrition in patients with nasopharyngeal carcinoma (NPC). Our study aims to develop a new nutritional assessment tool for NPC patients. METHODS AND ANALYSIS: NPC patients will be required to complete a risk factor questionnaire after obtaining their informed consent. The risk factor questionnaire will be used to collect potential risk factors for malnutrition. Univariate and multivariate logistic regression analyses will be used to identify risk factors for malnutrition. A new nutritional assessment tool will be developed based on risk factors. The new tool's performance will be assessed by calibration and discrimination. The bootstrapping will be used for internal validation of the new tool. In addition, external validation will be performed by recruiting NPC patients from another hospital. DISCUSSION: If the new tool is validated to be effective, it will potentially save medical staff time in assessing malnutrition and improve their work efficiency. Additionally, it may reduce the incidence of malnutrition and its adverse consequences. STRENGTHS AND LIMITATIONS OF THIS STUDY: The study will comprehensively analyze demographic data, disease status, physical examination, and blood sampling to identify risk factors for malnutrition. Furthermore, the new tool will be systematically evaluated, and validated to determine their effectiveness. However, the restricted geographical range may limit the generalizability of the results to other ethnicities. Additionally, the study does not analyze subjective indicators such as psychology. ETHICS AND DISSEMINATION: The ethical approval was granted by the Ethical Committee of the First Affiliated Hospital of Guangxi Medical University (NO. 2022-KT-GUI WEI-005) and the Second Affiliated Hospital of Guangxi Medical University (NO. 2022-KY-0752). CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2300071550.


Subject(s)
Malnutrition , Nasopharyngeal Neoplasms , Humans , China/epidemiology , Malnutrition/epidemiology , Nasopharyngeal Carcinoma/complications , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Neoplasms/complications , Nasopharyngeal Neoplasms/diagnosis , Nutrition Assessment , Nutritional Status
7.
Mol Cell Proteomics ; 23(3): 100729, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38309569

ABSTRACT

Diagnosing, predicting disease outcome, and identifying effective treatment targets for virus-related cancers are lacking. Protein biomarkers have the potential to bridge the gap between prevention and treatment for these types of cancers. While it has been shown that certain antibodies against EBV proteins could be used to detect nasopharyngeal carcinoma (NPC), antibodies targeting are solely a tiny part of the about 80 proteins expressed by the EBV genome. Furthermore, it remains unclear what role other viruses play in NPC since many diseases are the result of multiple viral infections. For the first time, this study measured both IgA and IgG antibody responses against 646 viral proteins from 23 viruses in patients with NPC and control subjects using nucleic acid programmable protein arrays. Candidate seromarkers were then validated by ELISA using 1665 serum samples from three clinical cohorts. We demonstrated that the levels of five candidate seromarkers (EBV-BLLF3-IgA, EBV-BLRF2-IgA, EBV-BLRF2-IgG, EBV-BDLF1-IgA, EBV-BDLF1-IgG) in NPC patients were significantly elevated than controls. Additional examination revealed that NPC could be successfully diagnosed by combining the clinical biomarker EBNA1-IgA with the five anti-EBV antibodies. The sensitivity of the six-antibody signature at 95% specificity to diagnose NPC was comparable to the current clinically-approved biomarker combination, VCA-IgA, and EBNA1-IgA. However, the recombinant antigens of the five antibodies are easier to produce and standardize compared to the native viral VCA proteins. This suggests the potential replacement of the traditional VCA-IgA assay with the 5-antibodies combination to screen and diagnose NPC. Additionally, we investigated the prognostic significance of these seromarkers titers in NPC. We showed that NPC patients with elevated BLLF3-IgA and BDLF1-IgA titers in their serum exhibited significantly poorer disease-free survival, suggesting the potential of these two seromarkers as prognostic indicators of NPC. These findings will help develop serological tests to detect and treat NPC in the future.


Subject(s)
Nasopharyngeal Neoplasms , Proteome , Humans , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Neoplasms/diagnosis , Herpesvirus 4, Human/genetics , Capsid Proteins , Antigens, Viral , Biomarkers , Immunoglobulin G , Immunoglobulin A
10.
Clin Epigenetics ; 16(1): 11, 2024 01 11.
Article in English | MEDLINE | ID: mdl-38212818

ABSTRACT

BACKGROUND: As an oncovirus, EBV is associated with multiple cancers, including solid tumors and hematological malignancies. EBV methylation plays an important role in regulating tumor occurrence. However, the EBV methylation profiles in EBV-associated tumor tissues are poorly understood. RESULTS: In this study, EBV methylation capture sequencing was conducted in several different tumor tissue samples, including NPC, EBVaGC, lung LELC and parotid LELC. Besides, EBV capture sequencing and following qMSP were performed on nasopharyngeal brushing samples from NPC and nasal NKTCL patients. Our results showed that the EBV genome among different types of tumors displayed specific methylation patterns. Among the four types of tumors from epithelial origin (NPC, EBVaGC, lung LELC and parotid LELC), the most significant differences were found between EBVaGC and the others. For example, in EBVaGC, all CpG sites within 1,44,189-1,45,136 bp of the EBV genome sequence on gene RPMS1 were hyper-methylated compared to the others. Differently, significant differences of EBV CpG sites, particularly those located on gene BILF2, were observed between NPC and nasal NKTCL patients in nasopharyngeal brushing samples. Further, the methylated level of BILF2 was further detected using qMSP, and a diagnostic model distinguishing NPC and nasal NKTCL was established. The AUC of the model was 0.9801 (95% CI 0.9524-1.0000), with the sensitivity and specificity of 98.81% (95% CI 93.63-99.94%) and 76.92% (95% CI 49.74-91.82%), respectively. CONCLUSIONS: Our study reveals more clues for further understanding the pathogenesis of EBV, and provides a possibility for distinguishing EBV-related tumor by detecting specific EBV CpG sites.


Subject(s)
Carcinoma , Lymphoma, T-Cell , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/genetics , Herpesvirus 4, Human/genetics , DNA Methylation , Carcinoma/genetics , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/genetics , Lymphoma, T-Cell/genetics
11.
Cancer Cell ; 42(3): 464-473.e3, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38242125

ABSTRACT

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.


Subject(s)
Carcinoma , Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/pathology , Neoplasm Staging , Herpesvirus 4, Human , Prognosis , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/pathology , Epstein-Barr Virus Infections/pathology , Carcinoma/pathology , Retrospective Studies
12.
Curr Probl Cancer ; 48: 101060, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38211418

ABSTRACT

BACKGROUND: Treatment delays have frequently been observed in cancer patients. Whether the treatment delays would impair the survival of patients with nasopharyngeal carcinoma (NPC) is still unclear. METHODS: The data were derived from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Patients were divided into groups of timely treatment (<1 month), intermediate delay (1 and 2 months), and long delay (3-6 months). The influence of different treatment delay intervals on long-term survival was evaluated by multivariate Cox regression analysis. RESULTS: In total, 2,048 patients with NPC were included in our study. There were 551 patients in the early stage (I, II stage: 26.9 %) and 1,497 patients in the advanced stage (III, IV stage: 73.1 %). No significant difference in overall survival (OS) or cancer-specific survival (CSS) was observed among the groups with various treatment delay intervals (p = 0.48 in OS and p = 0.43 in CSS, respectively). However, upon adjusting for covariates, a significantly improved OS probability emerged in patients with intermediate treatment delays compared to those who received timely interventions in both the entire study population (adjustedHazard Ratio (aHR)=0.86, 95 % CI: 0.74-0.99, p = 0.043) and the subgroup with advanced stage (aHR=0.85, 95 % CI: 0.72-1.00, p = 0.049). Regarding the CSS probability, similar associations were also observed in the entire study population (aHR=0.84, 95 % CI: 0.71-0.98, p = 0.030) as well as the advanced-stage patients (aHR=0.83, 95 % CI: 0.70-0.99, p =  0.038). CONCLUSIONS: Our results revealed that treatment delays are not associated with worse survival of NPC patients. Tumor-specific characteristics and subsequent treatment modalities play more pivotal roles in the prognosis of NPC.


Subject(s)
Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Cohort Studies , Neoplasm Staging , Prognosis , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/therapy
13.
J Natl Cancer Inst ; 116(5): 665-672, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38171488

ABSTRACT

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.


Subject(s)
Early Detection of Cancer , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Magnetic Resonance Imaging , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/pathology , Male , Middle Aged , Female , Magnetic Resonance Imaging/methods , Early Detection of Cancer/methods , Adult , Herpesvirus 4, Human/isolation & purification , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/pathology , Prospective Studies , Aged , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , DNA, Viral/blood , Carcinoma/diagnostic imaging , Carcinoma/virology , Carcinoma/diagnosis , Carcinoma/pathology , Sensitivity and Specificity , Endoscopy/methods , Neoplasm Staging , Mass Screening/methods , Contrast Media/administration & dosage
15.
J Gene Med ; 26(1): e3653, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38282154

ABSTRACT

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly aggressive and metastatic malignancy originating in the nasopharyngeal tissue. Pyroptosis is a relatively newly discovered, regulated form of necrotic cell death induced by inflammatory caspases that is associated with a variety of diseases. However, the role and mechanism of pyroptosis in NPC are not fully understood. METHODS: We analyzed the differential expression of pyroptosis-related genes (PRGs) between patients with and without NPC from the GSE53819 and GSE64634 datasets of the Gene Expression Omnibus (GEO) database. We mapped receptor operating characteristic profiles for these key PRGs to assess the accuracy of the genes for disease diagnosis and prediction of patient prognosis. In addition, we constructed a nomogram based on these key PRGs and carried out a decision curve analysis. The NPC patients were classified into different pyroptosis gene clusters by the consensus clustering method based on key PRGs, whereas the expression profiles of the key PRGs were analyzed by applying principal component analysis. We also analyzed the differences in key PRGs, immune cell infiltration and NPC-related genes between the clusters. Finally, we performed differential expression analysis for pyroptosis clusters and obtained differentially expressed genes (DEGs) and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. RESULTS: We obtained 14 differentially expressed PRGs from GEO database. Based on these 14 differentially expressed PRGs, we applied least absolute shrinkage and selection operator analysis and the random forest algorithm to obtain four key PRGs (CHMP7, IL1A, TP63 and GSDMB). We completely distinguished the NPC patients into two pyroptosis gene clusters (pyroptosis clusters A and B) based on four key PRGs. Furthermore, we determined the immune cell abundance of each NPC sample, estimated the association between the four PRGs and immune cells, and determined the difference in immune cell infiltration between the two pyroptosis gene clusters. Finally, we obtained and functional enrichment analyses 259 DEGs by differential expression analysis for both pyroptosis clusters. CONCLUSIONS: PRGs are critical in the development of NPC, and our research on the pyroptosis gene cluster may help direct future NPC therapeutic approaches.


Subject(s)
Nasopharyngeal Neoplasms , Pyroptosis , Humans , Pyroptosis/genetics , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/genetics , Multigene Family , Cluster Analysis , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/genetics , Endosomal Sorting Complexes Required for Transport
16.
Clin Pharmacol Ther ; 115(5): 993-1006, 2024 May.
Article in English | MEDLINE | ID: mdl-38037868

ABSTRACT

Circulating tumor DNA (ctDNA) analysis increasingly provides a promising minimally invasive alternative to tissue biopsies in precision oncology. However, there are no ctDNA analysis approaches available in nasopharyngeal carcinoma (NPC) and current methods of ctDNA mutation profiling have limited resolution because of the high background noise and false-positive rate caused by benign variants in plasma cell-free DNA (cfDNA), majorly generated during clonal hematopoiesis. Although personalized parallel white blood cell genome sequencing suppresses the noise of clonal hematopoiesis variances, the system cost and complexity restrict its extensive application in clinical settings. We developed Matched WBC Genome sequencing Independent CtDNA profiling (MaGIC) approaches, which synergically integrated a ctDNA capturing panel for a hybrid capture cfDNA deep sequencing, in silico background elimination, and a reliable readout measurement. We profiled the ctDNAs of 80 plasma samples from 40 patients with NPC before and during chemotherapy by MaGICs. In addition, the public cfDNA sequencing data and The Cancer Genome Atlas project data were analyzed by MaGICs to evaluate their application in other scenarios of patient classification. The MaGIC version-2 has the ability to predict the chemosensitivity of patients with NPC with high accuracy by utilizing a single sample of liquid biopsy from each patient prior to a standardized treatment regimen. Moreover, both versions of MaGICs are of ideal performance in the diagnosis of patients with prostate cancer by liquid biopsy and prognosis prediction of multiple cancers by tissue biopsy. This study has the potential to enhance the sensitivity and expand the application scope of ctDNA detection, independently of other paired genome sequencing methods. As a result, it might further increase the clinical utilization of liquid biopsy based on ctDNA.


Subject(s)
Circulating Tumor DNA , Nasopharyngeal Neoplasms , Prostatic Neoplasms , Male , Humans , Circulating Tumor DNA/genetics , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/genetics , Precision Medicine , Mutation , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/genetics , Biomarkers, Tumor/genetics , High-Throughput Nucleotide Sequencing/methods
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123747, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38091653

ABSTRACT

Nasopharyngeal carcinoma (NPC) is a malignant tumor in head and neck. Early diagnosis can effectively improve the survival rate of patients. Nasopharyngeal exfoliative cytology, as a convenient and noninvasive auxiliary diagnostic method, is suitable for the population screening of NPC, but its diagnostic sensitivity is low. In this study, an electroporation-based SERS technique was proposed to detect and screen the clinical nasopharyngeal exfoliated cell samples. Firstly, nasopharyngeal swabs was used to collected the nasopharyngeal exfoliated cell samples from NPC patients (n = 54) and healthy volunteers (n = 60). Then, gold nanoparticles, as the Raman scattering enhancing substrates, were rapidly introduced into cells by electroporation technique for surface-enhanced Raman scattering (SERS) detection. Finally, SERS spectra combined with principal component analysis (PCA) and linear discriminant analysis (LDA) were employed to diagnose and distinguish NPC cell samples. Raman peak assignments combined with spectral differences reflected the biochemical changes associated with NPC, including nucleic acid, amino acid and carbohydrates. Based on the PCA-LDA approach, the sensitivity, specificity and accuracy of 98.15 %, 96.67 % and 97.37 %, respectively, were achieved for screening NPC. This study offers valuable assistance for noninvasive NPC auxiliary diagnosis, and has grate potential in expanding the application of the SERS technique in clinical cell sample testing.


Subject(s)
Metal Nanoparticles , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/chemistry , Nasopharyngeal Neoplasms/pathology , Gold/chemistry , Metal Nanoparticles/chemistry , Spectrum Analysis, Raman/methods , Discriminant Analysis , Electroporation , Principal Component Analysis
20.
Am J Surg Pathol ; 48(1): 54-58, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37779503

ABSTRACT

Assessment of tumor-associated stroma has shown a reliable prognostic value in recent research. We evaluated the prognostic value of tumor-stroma ratio (TSR) in a large multicenter cohort of nasopharyngeal carcinoma (NPC). We used the conventional hematoxylin and eosin-stained slides of 115 cases of NPC to assess TSR as described in recent guidelines. The amount of tumor-associated stroma was assessed as a percentage and then tumors were classified as stroma-high (>50%) or stroma-low (≤50%). Kaplan-Meier curves, χ 2 test, and Cox regression univariable and multivariable analyses were carried out. A total of 48 (41.7%) tumors were stroma-high and 67 (58.3%) tumors were stroma-low. In the Cox regression multivariable analysis, the tumors categorized as stroma-high were associated with a worse overall survival with a hazard ratio of 2.30 (95% CI: 1.27-4.15, P =0.006) and with poor disease-specific survival (hazard ratio=1.87, 95% CI: 1.07-3.28, P =0.029). The assessment of TSR in NPC is simple and cost-effective, and it has a significant prognostic value. TSR can aid in risk stratification and clinical decision-making in NPC.


Subject(s)
Nasopharyngeal Neoplasms , Stromal Cells , Humans , Prognosis , Nasopharyngeal Carcinoma/pathology , Proportional Hazards Models , Stromal Cells/pathology , Nasopharyngeal Neoplasms/diagnosis
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