Nasopharyngeal Carcinoma Group Research Articles

The Treatment of Primary Lymphoepithelioma-Like Carcinoma in the Head and Neck and Nasopharyngeal Carcinoma.

An uncommon cancer, lymphoepithelioma-like carcinoma (LELC) resembles undifferentiated nasopharyngeal carcinoma (NPC) histologically. The aim is mainly to introduce the diagnosis and treatment of LELC and compare it with NPC in our descriptive study. A total of 278 patients with NPC and 157 patients with head and neck LELC had their medical records examined in this study. The propensity score matching (PSM) approach was employed to attain a 1:1 match between the LELC and NPC groups. Kaplan-Meier analysis was performed for overall survival (OS) of LELC and NPC. To determine their predictive values for OS, univariate and multivariate Cox regression analyses with significant survival differences (p < 0.05) were carried out. Similar to NPC, 107 (68.2%) LELC cases had Epstein-Barr virus (EBV) infection. LELC of the parotid glands was present in nearly 46.5% of patients with head and neck LELC. Most patients were treated with surgery with neck dissection. After PSM, LELC had similar 5-year OS rates to NPC (81.6% vs. 79.0%). LELC was less prone to distant metastasis compared to NPC. Age, T stage, N stage, and distant metastases were found to be substantially correlated with the outcome of LELC, according to the multivariate Cox regression analysis (p < 0.05). EBV infection in the head and neck has been associated with LELC and NPC. When compared to NPC, LELC is more likely to arise in the salivary glands and has a lower incidence of distant metastasis. Surgery with neck dissection is the primary treatment for LELC.

Identifying biomarkers for nasopharyngeal carcinoma diagnosis and chemoradiotherapy response using serum endogenous small molecules profiling

Changes in metabolic characteristics are important features of tumor progression and prognosis, including nasopharyngeal carcinoma (NPC). Identifying serum metabolites as potential diagnostic and chemoradiotherapy response biomarkers for NPC is therefore crucial. In this study, ultra-performance liquid chromatography coupled with linear ion trap quadrupole orbitrap high-resolution mass spectrometry (UPLC-LTQ-Orbitrap MS) was used to analyze metabolic variations among controls, NPC patients, and NPC patients undergoing chemoradiotherapy (CRT). Univariate and multivariate analyses revealed seven differential metabolites between the control and NPC groups and eleven metabolites between the CRT and NPC groups. Five common metabolites, gluconic acid, palmitic acid, LysoPC (15:0/0:0), stearic acid, and LysoPC (20:2(11Z,14Z)/0:0), were consistently altered across groups. Notably, the first four metabolites were adjusted closer to normal after chemoradiotherapy, while this change is not reflected at LysoPC (20:2(11Z,14Z)/0:0). These common metabolites were enriched in five pathways. These findings underscore the importance of serum metabolite profiling in NPC diagnosis and treatment response assessment and offer a promising foundation for further clinical research.

Characterization of unique pattern of immune cell profile in patients with nasopharyngeal carcinoma through flow cytometry and machine learning.

In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell profile for patients with NPC and used flow cytometry and machine learning (ML) to identify the characteristics of this profile. After isolation of circulating leukocytes, the proportions of 104 immune cell subsets were compared between NPC group and the healthy control group (HC). Data obtained from the immune cell profile were subjected to ML training to differentiate between the immune cell profiles of the NPC and HC groups. We observed that subjects in the NPC group presented higher proportions of T cells, memory B cells, short-lived plasma cells, IgG-positive B cells, regulatory T cells, MHC II+ T cells, CTLA4+ T cells and PD-1+ T cells than subjects in the HC group, indicating weaker and compromised cellular and humoral immune responses. ML revealed that monocytes, PD-1+ CD4 T cells, memory B cells, CTLA4+ CD4 Treg cells and PD-1+ CD8 T cells were strongly contributed to the difference in immune cell profiles between the NPC and HC groups. This alteration can be fundamental in developing novel immunotherapies for NPC.

Study on carotid artery stenosis after radiotherapy for nasopharyngeal carcinoma

ObjectiveThis study investigated carotid artery stenosis (CAS) and associated risk factors in patients with nasopharyngeal carcinoma (NPC) post-radiotherapy.Materials and methodsThe observation group comprised 86 reexamined patients with NPC, divided into Group 1 and Group 2 based on post-radiotherapy duration, alongside 34 newly diagnosed patients with NPC (Group 0). Carotid artery ultrasonography and chi-square analysis were performed.ResultsModerate-to-severe vascular abnormalities were exclusively in Group 2. Considering mild vascular abnormalities as the standard, the overall vascular abnormality rates in Group 2 and Group 0 were 65.9% and 41.2%, respectively. In Group 2 and Group 0, the abnormality rates for unilateral carotid artery (UCA), common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA) were 47.4% and 30.9%, 44.3% and 22.1%, 44.3% and 16.2%, and 39.8% and 5.9%, respectively. Comparing group 1 to group 0, only UCA abnormalities were statistically significant (45.4% vs. 30.9%). Considering moderate-to-severe vascular abnormalities as the standard, Group 2 had higher overall vascular, UCA, CCA, ICA, and ECA abnormality rates compared to Group 0. The age at revisit over 45 years, T stage, and N stage may influence CAS.ConclusionRadiation increasing CAS incidence after 3 years. So, regular examinations are recommended to dynamically monitor CAS after 3 years of radiotherapy.

Abnormal variation and prognostic significance of circulating immune cells in patients with nasopharyngeal carcinoma treated with chemoradiotherapy: a prospective cohort study.

Circulating immune cells are associated with tumor development and poor prognosis in multiple solid tumors. However, the circulating immune-cell profile of nasopharyngeal carcinoma (NPC) remains largely unknown. Therefore, we aimed to determine the changes in immune status and the prognostic significance of circulating immune cells before and after chemoradiotherapy (CRT) in patients, which can provide clinicians with valuable insights to optimize treatment strategies, monitor immune function, and personalize interventions, ultimately improving patient outcomes. Circulating immune cells before and after CRT in 77 patients with NPC and in 30 healthy controls were measured with flow cytometry. A thorough follow-up was conducted to assess prognosis outcomes, including local failure-free rate (LFFR), distant failure-free rate (DFFR), disease-free survival (DFS), and overall survival (OS). The differences of the subpopulation distribution in the two groups were determined by t-tests or Mann-Whitney tests. The paired t-test or Wilcoxon matched-pairs signed rank test was used to compare differences in lymphocyte subsets before and after CRT. The prognostic significance of lymphocyte subsets was evaluated by Kaplan-Meier analysis and Cox proportional hazards model. Compared with the control group, the NPC group showed significant decreases in the proportions of CD3+ cells, CD4+ T cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio (P<0.05) but a significant increase in the proportion of natural killer (NK) cells (P<0.05). After CRT, the proportions of CD4+ cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio were markedly decreased (P<0.05), while the proportions of CD8+ T cells and NK cells were significantly increased (P<0.05). Multivariate analysis showed that a lower percentage of CD19+ B cells [hazard ratio (HR) 6.550, 95% CI: 1.661-25.831; P=0.007] and a positive test for Epstein-Barr virus (EBV) DNA (HR 0.261, 95% CI: 0.074-0.926; P=0.038) before treatment independently predicted worse 5-year OS (P<0.05). The disproportion of circulating immune cells was observed in patients with NPC before treatment. CRT further aggravated immune dysfunction. Notably, a lower percentage of CD19+ B cells and EBV DNA-positive status before treatment were independent predictors of a worse prognosis. Thus, the measurement of circulating immune cells may help elucidate immune function status and predict the outcomes of patients with NPC.

Risk of temporal lobe necrosis between proton beam and volumetric modulated arc therapies in patients with different head and neck cancers

BackgroundTo investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods.MethodsWe retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan–Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC.ResultsCompared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan–Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37–130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan–Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70).ConclusionOur study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.

Inhibitory mechanism of KIF3A gene on nasopharyngeal carcinoma stem cells.

To investigate the inhibitory mechanism of the KIF3A gene on nasopharyngeal carcinoma (NPC) tumor stem cells. Set up a blank control group (BCG), NPC group, and KIF3A silence (si-KIF3A) group. The BCG cells were nasopharyngeal normal epithelial cell line NP69, without any treatment, and were cultured routinely; The NPC group cells are human NPC cell line CNE2 cells, which are not subjected to any treatment and are cultured routinely; si-KIF3A group cells were cultured in the offspring of human NPC cell line CNE2 infected with Lentivirus knockdown KIF3A gene. CCK8 was used to detect the cell proliferation ability, Western blot and qPCR were used to detect protein and related mRNA expression, while cell migration and invasion were detected using Transwell. The KIF3A protein and mRNA in the NPC group were higher than those in the BCG (P<0.05), while those in the si-KIF3A group cells were lower compared to BCG cells (P<0.05). The cell proliferation, migration and invasion activity in the si-KIF3A group were reduced than those in BCG (P<0.05). Si-KIF3A group cells HIF-1, NF-κB was reduced than that of BCG (P<0.05). The expression level of HIF-1, NF-κB protein in si-KIF3A group cells was reduced compared to BCG cells (P<0.05). Knocking down the KIF3A gene can reduce the vitality of NPC stem cells, and inhibit the malignant phenotype of NPC stem cells, via inhibiting HIF-1 and NF-κB expression.

Clinical Significance of Serum Iron Metabolism-Related Markers in Patients with Nasopharyngeal Carcinoma

Introduction: It is known that iron metabolism is dysregulated in nasopharyngeal carcinoma (NPC). However, a meaningful assessment of the iron metabolic status in cancer patient is still under debate. This study aims to evaluate the status of iron metabolism, as well as to explore the correlation between those related serum markers and clinicopathological features of patients with NPC. Methods: Peripheral blood was collected from 191 pretreatment NPC patients and 191 healthy controls. The red blood cell parameters, plasma Epstein-Barr virus (EBV) DNA load, serum iron (SI), total iron-binding capacity (TIBC), transferrin, soluble transferrin receptor (sTFR), ferritin, and hepcidin were quantitatively detected. Results: The mean levels of hemoglobin and red blood cell count in the NPC group were significantly lower than those in the control group, while no statistical differences in mean MCV were found between the two groups. Median levels of SI, TIBC, transferrin, and hepcidin were significantly lower in the NPC group than in the control group. Compared to patients with the T1-T2 classification, patients with the T3-T4 classification exhibited significantly lower expression levels of SI and TIBC. Serum levels of ferritin and sTFR were significantly higher in patients with M1 classification than those with M0 classification. The EBV DNA load was associated with serum levels of sTFR and hepcidin. Conclusion: NPC patients had functional iron deficiency. The degree of iron deficiency was related to the tumor burden and metastasis of NPC. EBV might be involved in the regulation of iron metabolism in the host.

Association of the nasopharyngeal carcinoma and the subsequent open glaucoma development: a nationwide cohort study.

This study aimed to investigate the possible association between nasopharyngeal carcinoma (NPC) and following open angle glaucoma (OAG). A retrospective research applying the National Health Insurance Research Database (NHIRD) of Taiwan was conducted with a follow up period from January 1, 2000 to December 31, 2016. There were 4184 and 16736 participants that selected and categorized into the NPC and non-NPC groups after exclusion. The major outcome of our study was the development of OAG according to diagnostic codes, exam and managements. The Cox proportional hazard regression was employed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of OAG between the two groups. In this study, a numbers of 151 and 513 OAG episodes occurred in the NPC and non-NPC groups and the NPC population showed a significantly higher incidence of OAG compared to the non-NPC population in multivariable analysis (aHR: 1.293, 95% CI: 1.077-1.551, p = 0.0057). Besides, the cumulative probability of OAG was significantly higher in the NPC group than that in the non-NPC population (p = 0.0041). About other risk factor for OAG, age older than 40 years old, diabetes mellitus and persistent steroid usage were related to OAG occurrence (all p < 0.05). In conclusion, the NPC may be an independent risk factor of following OAG development.

Nasopharyngeal Carcinoma and Its Effect on Dry Eye Disease: A Nationwide Cohort Study.

The aim of the current study was to investigate the relationship between nasopharyngeal carcinoma (NPC) and dry eye disease (DED) using the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was conducted, and patients with an NPC diagnosis were included. Next, one NPC patient was matched to four non-NPC participants via demographic data and systemic comorbidities. In total, 4184 and 16,736 participants were enrolled in the NPC and non-NPC groups, respectively. The primary outcome was the development of DED one year after the diagnosis of NPC. Cox proportional hazard regression was applied to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of DED. In this study, 717 and 2225 DED cases were found in the NPC and non-NPC groups, respectively, and the NPC group showed a significantly higher incidence of DED development compared to the non-NPC group (aHR: 1.45, 95% CI: 1.33−1.58, p < 0.0001) in the multivariable analysis. The other covariates that were positively correlated with DED development included age over 40 years, an education level higher than senior high school, hypertension, DM, allergic pulmonary diseases, allergic otolaryngologic diseases, and allergic dermatological diseases (all p < 0.05). In conclusion, the presence of NPC is an independent risk factor for subsequent DED.

The Nasopharyngeal Carcinoma and Its Effect on the Infectious Eye Disease: A Nationwide Cohort Study.

The purpose of this study is to investigate the potential correlation between nasopharyngeal carcinoma (NPC) and both infectious keratitis and orbital cellulitis. The retrospective cohort study used the National Health Insurance Research Database (NHIRD) as a data source. A total number of 4184 patients with NPC diagnosis were selected and matched to 16,736 non-NPC patients via the propensity-score matching (PSM). The main outcomes are the development of infectious keratitis and orbital cellulitis according to diagnostic codes and related medications. The Cox proportional hazard regression was adopted to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of outcomes between the two groups. A total of 35 and 19 episodes of orbital cellulitis occurred in the NPC and non-NPC groups and the aHR was significantly higher in the NPC group (aHR: 1.34, 95% CI: 1.23−1.46, p = 0.0024). There were 2185 and 659 events of infectious keratitis in the NPC and non-NPC groups, and the NPC group revealed a significantly higher aHR than non-NPC group (aHR: 1.34, 95% CI: 1.23−1.46, p < 0.0001). Besides, the cumulative probability of infectious keratitis was significantly higher in the NPC group than the non-NPC group (p < 0.0001). The other risk factors of infectious keratitis include age from 20 to 30 years old, allergic respiratory diseases, allergic dermatological diseases, and external eye diseases (all p < 0.0001). In subgroup analyses, both the incidences of infectious keratitis (aHR: 1.33, 95% CI: 1.21−1.47) and orbital cellulitis (aHR: 2.36, 95% CI: 1.27−4.39) were significantly higher than the non-NPC group. The incidence of infectious keratitis was significantly higher in NPC patients without radiotherapy (aHR: 1.40, 95% CI: 1.26−1.55) compared to non-NPC population, while the rate of orbital cellulitis was similar between the NPC patients without radiotherapy (aHR: 0.76, 95% CI: 0.27−2.14) and non-NPC population. In conclusion, the existence of NPC associates with higher incidence of infectious keratitis which increases with NPC period, and the radiotherapy may be account for the higher rate of orbital cellulitis in NPC population.

Highly Efficient Blood Protein Analysis Using Membrane Purification Technique and Super-Hydrophobic SERS Platform for Precise Screening and Staging of Nasopharyngeal Carcinoma.

Early screening and precise staging are crucial for reducing mortality in patients with nasopharyngeal carcinoma (NPC). This study aimed to assess the performance of blood protein surface-enhanced Raman scattering (SERS) spectroscopy, combined with deep learning, for the precise detection of NPC. A highly efficient protein SERS analysis, based on a membrane purification technique and super-hydrophobic platform, was developed and applied to blood samples from 1164 subjects, including 225 healthy volunteers, 120 stage I, 249 stage II, 291 stage III, and 279 stage IV NPC patients. The proteins were rapidly purified from only 10 µL of blood plasma using the membrane purification technique. Then, the super-hydrophobic platform was prepared to pre-concentrate tiny amounts of proteins by forming a uniform deposition to provide repeatable SERS spectra. A total of 1164 high-quality protein SERS spectra were rapidly collected using a self-developed macro-Raman system. A convolutional neural network-based deep-learning algorithm was used to classify the spectra. An accuracy of 100% was achieved for distinguishing between the healthy and NPC groups, and accuracies of 96%, 96%, 100%, and 100% were found for the differential classification among the four NPC stages. This study demonstrated the great promise of SERS- and deep-learning-based blood protein testing for rapid, non-invasive, and precise screening and staging of NPC.

MicroRNA-145-5p modulates Krüppel-like factor 5 and inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma

BackgroundIn several human cancers, Krüppel-like factor 5 (KLF5), a zinc finger transcription factor, can contribute to both tumor progression or suppression; however, the precise role of KLF5 in nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, the association between KLF5 and microRNA-145-5p (miR-145-5p) in NPC cells was elucidated.ResultsOur results showed that KLF5 expression was up-regulated in NPC group compared to normal group. We found that KLF5 exhibited an oncogenic role in NPC cells. The upregulation of miR-145-5p inhibited the proliferation, migration, and invasion of NPC cells. It was observed that miR-145-5p could down-regulate the mRNA and protein expression of KLF5 in NPC cell lines. Additionally, the activity of focal adhesion kinase (FAK), a migration marker, was regulated by miR-145-5p and KLF5 in NPC cells.ConclusionsThe results of this study indicated that miR-145-5p could repress the proliferation, migration, and invasion of NPC cells via KLF5/FAK regulation, and could be a potential therapeutic target for patients with NPC.

Study of Three Potential Diagnostic Biomarkers in Nasopharyngeal Carcinoma Samples from Guilan, North of Iran.

Introduction Finding biomarkers for highly lethal cancers is a priority. Objective The current study was designed to understand the clinical significance of vascular endothelial growth factor (VEGF), latent membrane protein 1 (LMP1), and tumor necrosis factor-α (TNF-α) expression as the biomarkers, and evaluate their correlation with each other, in nasopharyngeal carcinoma (NPC) in the province of Guilan, North of Iran. Methods Gene expression was evaluated in 25 formalin-fixed paraffin-embedded (FFPE) blocks from cases of confirmed NPC and 20 FFPE samples of non-NPC by quantifying messenger ribonucleic acid (mRNA) and protein levels, using real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) methods, respectively. Furthermore, the correlations among the protein levels of different genes, along with the patients' demographic characteristics were assessed. Results Our findings on mRNA and protein levels demonstrated that the expression of the LMP1 gene in the NPC group was significantly elevated compared with that of the non-NPC group. In addition, the protein levels in the NPC group indicated a positive and significant correlation between LMP1 and VEGF expression. It was noted that both protein and mRNA levels showed no significant differences in the expression of TNF-α and VEGF genes between the NPC and control groups. Furthermore, there was no significant relationship between the expression of these proteins and the demographic characteristics of NPC patients. Conclusion Overall, a significant increase in LMP1 expression was observed in NPC patients, which may serve as a diagnostic biomarker for NPC. Also, LMP1 might be involved in NPC progression by inducing VEGF gene expression.

Head and Neck Cancer Types and Risks of Cervical-Cranial Vascular Complications within 5 Years after Radiation Therapy.

Background and purpose: to investigate the frequency of cervical–cranial vascular complications soon after radiation therapy (RT) and identify differences among patients with various types of head and neck cancer (HNC). Methods: We enrolled 496 patients with HNC who had received their final RT dose in our hospital. These patients underwent carotid duplex ultrasound (CDU) for monitoring significant carotid artery stenosis (CAS). Brain imaging were reviewed to detect vertebral, intracranial artery stenosis, or preexisted CAS before RT. Primary outcome was significant CAS at the internal or common carotid artery within first 5 years after RT. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of significant CAS between the groups using Kaplan–Meier and Cox-regression analyses. Results: Compared to the NPC group, the non-NPC group had a higher frequency of significant CAS (12.7% vs. 2.0%) and were more commonly associated with significant CAS after adjusting the covariates (Adjusted hazard ratio: 0.17, 95% confident interval: 0.05–0.57) during the follow-up period. All the non-NPC subtypes (oral cancer/oropharyngeal, hypopharyngeal, and laryngeal cancers) were associated with higher risks of significant CAS than the NPC group (p < 0.001 respectively). Conclusion: Significant CAS was more frequently noted within 5 years of RT among the patients with non-NPC HNC than among the patients with NPC. Scheduled carotid artery surveillance and vascular risk monitoring should be commenced earlier for patients with non-NPC HNC. By contrast, vascular surveillance could be deferred to 5 years after RT completion in NPC patients.

Expression of pepsin in nasopharyngeal carcinoma and its correlation with quality of life after radiotherapy

Objective: By analyzing the expression of pepsin in nasopharyngeal carcinoma (NPC) tissues, to investigate the correlation between laryngeal reflux (LPR) and NPC, as well as the effect of LPR on the quality of life of patients with NPC after radiotherapy. Methods: A total of 133 patients with NPC who underwent radiotherapy at the Department of Otorhinolaryngology of the Affiliated Hospital of Guizhou Medical University and the Affiliated Cancer Hospital of Guizhou Medical University from 2005 to 2019 were enrolled consecutively, including 90 males and 43 females, aged (44.32±7.47) years old. At the same period, 58 patients with chronic nasopharyngitis who underwent nasopharyngeal biopsy were selected as the control group. Immunohistochemical method was used to detect the expression of pepsin in nasopharyngeal specimens of the two groups. In addition, 188 normal individuals were selected as the normal group in the same period. NPC patients before and within 6 months after radiotherapy were inverstigated by the General Information Questionnaire and the Quality of Life Scale, and the pepsin levels in saliva of NPC patients before and after radiotherapy and the individuals in normal group were measured. SPSS 21.0 software was used for statistical analysis. Results: Pepsin expression in 133 specimens of NPC patients was strongly positive in 24 cases (18.05%), positive in 21 cases (15.79%), weakly positive in 69 cases (51.88%), and negative in 19 cases (14.29%). The specimens of control group had 10 cases of weakly positive (17.24%), 48 cases of negative (82.76%), but no strong positive or positive pepsin expression. The rate of positive pepsin expression in the NPC group was higher than that in the control group, with a statistically significant (χ2=83.15, P<0.001). The pepsin content in the saliva of NPC patients after radiotherapy ((30.31±7.82) ng/ml) was higher than that before radiotherapy ((20.47±8.21) ng/ml) and the normal group (5.11±2.13) ng/ml), and the pepsin content in saliva before radiotherapy was higher than that in the normal group, and all differences were statistically significant (all P<0.05). After radiotherapy, the five functional domains of quality of life and overall quality of life of NPC patients decreased, while the related symptom scores increased (all P<0.05). Multiple linear regression analysis showed that pepsin content in saliva was the influential factor of five functional domains of quality of life, related symptoms and overall quality of life in NPC patients after radiotherapy (all P<0.05). Conclusion: The positive rate of pepsin expression in NPC tissues is high, and the pepsin in saliva before and after radiotherapy of NPC patients is significantly higher than that in normal, suggesting that LPR may be involved in the process of NPC and affect the quality of life after radiotherapy in NPC patients.

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.

Concurrent chemoradiation therapy is associated with an accelerated risk of cardiovascular autonomic dysfunction in patients with nasopharyngeal carcinoma: A 9-year prospective follow-up study

BackgroundConcurrent chemoradiation therapy (CCRT) is the mainstay treatment for patients with nasopharyngeal carcinoma (NPC). Baroreflex impairment can be a late sequela in patients after neck radiotherapy. We hypothesized that cardiovascular autonomic dysfunction is a progressive process that can begin after CCRT and persists for a longer period. MethodsCardiovascular autonomic function was assessed in 29 newly diagnosed patients with NPC using standardized measures including heart rate response to deep breathing (HRDB), Valsalva ratio (VR), baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV), biomarkers of oxidative stress, and inflammation at three different time points (baseline, immediately after CCRT, and 9 years after enrollment). A healthy control group was recruited for the comparison. ResultsAlthough there was an aging effect on autonomic parameters in both groups during the 9 years of follow-up, the between-group comparison showed that there was a significant decrease in HRDB, VR, and HRV at the 9th year of follow-up in the NPC group. Repeated measures ANOVA after controlling for age and sex showed that both HRDB and triangle index of HRV had statistically significant differences between the two groups. ConclusionBased on our results, cardiovascular autonomic dysfunction after CCRT is a progressive and dynamic process. Cardiovagal impairment occurs in the early phase and persists in decline, while adrenergic dysfunction is significant only after a 9-year follow-up. In contrast to the current opinion, our study showed that both afferent and efferent baroreflex pathways can be involved after CCRT.

Radiotherapy Is Associated with an Accelerated Risk of Carotid Atherosclerosis in Patients with Nasopharyngeal Carcinoma: A Nine-Year Prospective Follow-Up Study.

Simple SummaryRadiotherapy has become a common treatment modality for nasopharyngeal carcinoma, and concurrent chemoradiation therapy prolongs the survival of patients. Radiotherapy leads to the increased generation of reactive oxygen species and free radicals to destroy abnormal cell growths within normal cell environmental conditions. However, the late effects on “bystander” organs (e.g., extracranial arteries) among survivors after radiotherapy have become increasingly prevalent. This study showed radiation-related extracranial vasculopathy is a progressive process that begins immediately after radiotherapy with significantly increased carotid IMT compared to the control group during the 9-year follow-up. Chronic inflammation and oxidative stress might serve to drive the process and also contribute to increased platelet activation.Radiation-related extracranial vasculopathy is a common late effect after radiation in patients with nasopharyngeal carcinoma (NPC). We proposed the hypothesis that radiation-related extracranial vasculopathy is a progressive process that can begin immediately after radiotherapy and persist for a longer period, and inflammation and oxidative stress may play a pivotal role in this process. Thirty-six newly diagnosed NPC patients were assessed with B-mode ultrasound for the common carotid artery (CCA) intima media thickness (IMT) measurement as well as surrogate markers at three different stages (baseline, immediately after concurrent chemoradiation therapy (CCRT), and 9 years after enrollment). A healthy control group was also recruited for comparison. Surrogate markers including a lipid profile, HbA1c, inflammation, oxidative stress, and platelet activation markers were assessed. The mean CCA IMT in the NPC group were increased immediately after CCRT (p = 0.043). The mean CCA IMT value after a 9-year follow-up also showed a significant increase in NPC and control group, respectively (p < 0.0001 and p < 0.0001, paired t test). The annual increase mean CCA IMT (mm) was 0.053 ± 0.025 and 0.014 ± 0.013 in NPC and control group, respectively (p < 0.0001). The baseline high sensitivity CRP (hs-CRP), thiol, TBARS, and CD63 level were significantly higher in the NPC group (hs-CRP, p = 0.001, thiol, p < 0.0001, TBARS, p = 0.05, and CD63 level, p = 0.04). The thiol and TBARS levels were significantly lower in NPC patients immediately after CCRT (thiol, p < 0.0001, and TBARS, p = 0.043). The CD62P level was significantly higher while the thiol level was significantly lower in the NPC group after a 9-year follow-up (CD62P level, p = 0.007; and thiol level, p = 0.004). Radiation-related extracranial vasculopathy is a progressive process that begins immediately after radiotherapy with significantly increased carotid IMT compared to the control group during the 9-year follow-up. Chronic inflammation and oxidative stress might serve to drive the process and also contribute to increased platelet activation.

ALDH1B1 predicts poor survival for locally advanced nasopharyngeal carcinoma patients.

BackgroundDistant metastasis and local recurrence remain the major reasons of treatment failure in locally advanced nasopharyngeal carcinoma (NPC). Therefore, exploring novel biomarkers for prognosis and sensitivity of radiotherapy in locally advanced NPC is crucial. This retrospective study evaluates the expression and prognostic value of aldehyde dehydrogenase 1B1 (ALDH1B1) for locally advanced NPC patients.MethodsSixty-seven locally advanced NPC patients and 22 chronic nasopharyngitis patients between September 2012 to November 2016 at The First Affiliated Hospital of University of South China were enrolled in this study. The expression of ALDH1B1 in tumor tissues were detected by using immunohistochemistry (IHC).ResultsSignificant difference was observed between NPC groups and Pharyngitis tissues groups, and NPC groups has a higher ratio of high ALDH1B1 expression. ALDH1B1 expression were significantly associated with age and radiotherapy response. The Kaplan-Meier analysis indicated that patients with high ALDH1B1 expression had a poor prognosis both in overall survival (OS) and progression-free survival (PFS). Univariate analysis found that age, radiotherapy response and ALDH1B1 expression were correlated with OS. Besides, factors affecting PFS are radiotherapy response and ALDH1B1 expression. Multivariate analysis revealed that radiotherapy response and ALDH1B1 expression were the independent prognostic factors for OS, whereas radiotherapy response was for PFS.ConclusionsThe expression of ALDH1B1 was correlated with age and radiotherapy response. Patients with high ALDH1B1 expression show a poor prognosis both in OS and DFS. ALDH1B1 expression were the independent prognostic factors for OS.