Overall Survival Of Nasopharyngeal Carcinoma Patients Research Articles

Characteristics and treatment of epistaxis in nasopharyngeal carcinoma

ObjectivesTo analyze the risk factors and explore effective treatments for epistaxis in nasopharyngeal carcinoma (NPC) patients. MethodsFrom March 2006 to February 2020, 351 epistaxis patients visited our center and 195 patients meeting the inclusion criteria were enrolled in the study. Characteristics and treatments, including step-up hemostatic treatment (including medication, anterior ± posterior nostril packing, or further surgical hemostasis) and the CTPI emergency hemostasis method (including common carotid artery compression, tracheotomy / intubation, packing of nasal and nasopharynx, and interventional treatment), were analyzed. ResultsThe median total bleeding volume was 100.0 ml (range 20–4430 ml). 126 (64.6 %) and 69 (35.4 %) patients suffered from non-massive epistaxis and massive epistaxis. The 1-year overall survival (OS) rate was 60.1 % for patients with massive epistaxis and 97.3 % for those with non-massive epistaxis treated with step-up hemostatic treatment. Among patients with massive epistaxis, the 1-year OS rate was 80.0 % for those who received CTPI and 13.3 % for those who received step-up hemostatic treatment. ConclusionICA exposure and hemostasis failure was adverse prognostic factors for OS in NPC patients with epistaxis. The step-up hemostatic treatment is effective for controlling non-massive epistaxis. The CTPI emergency method might be an effective hemostasis treatment for NPC patients with massive epistaxis, especially those with PRNN and ICA exposure.

A positive feedback loop between PLD1 and NF-κB signaling promotes tumorigenesis of nasopharyngeal carcinoma

Phospholipase D (PLD) lipid-signaling enzyme superfamily has been widely implicated in various human malignancies, but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma (NPC). Here, we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis. Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines, correlating with worse disease-free and overall survival in NPC patients. Functional assays further elucidate the oncogenic role of PLD1, demonstrating its pivotal promotion of critical tumorigenic processes such as cell proliferation and migration in vitro, as well as tumor growth in vivo. Notably, our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression. Specifically, PLD1 enhances NF-κB activity by facilitating the phosphorylation and nuclear translocation of RELA, which in turn binds to the promoter of PLD1, augmenting its expression. Moreover, RELA overexpression markedly rescues the inhibitory effects in PLD1-depleted NPC cells. Importantly, the application of the PLD1 inhibitor, VU0155069, substantially inhibits NPC tumorigenesis in a patient-derived xenograft model. Together, our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.

LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein

Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.

Triglyceride-inflammation score established on account of random survival forest for predicting survival in patients with nasopharyngeal carcinoma: a retrospective study.

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. 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. 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. 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.

Development and internal validation of a nomogram based on peripheral blood inflammatory markers for predicting prognosis in nasopharyngeal carcinoma.

Inflammatory markers, including the product of neutrophil count, platelet count, and monocyte count divided by lymphocyte count (PIV) and the platelet-to-white blood cell ratio (PWR), have not been previously reported as prognostic factors in nasopharyngeal carcinoma (NPC) patients. In order to predict overall survival (OS) in NPC patients, our goal was to create and internally evaluate a nomogram based on inflammatory markers (PIV, PWR). A retrospective study was done on patients who received an NPC diagnosis between January 2015 and December 2018. After identifying independent prognostic indicators linked to OS using Cox proportional hazards regression analysis, we created a nomogram with the factors we had chosen. A total of 630 NPC patients in all were split into training (n = 441) and validation sets (n = 189) after being enrolled in a population-based study in 2015-2018 and monitored for a median of 5.9 years. In the training set, the age, PIV, and PWR, selected as independent predictors for OS via multivariate Cox's regression model, were chosen to develop a nomogram. Both training and validation cohorts had C-indices of 0.850 (95% confidence interval [CI]: 0.768-0.849) and 0.851 (95% CI: 0.765-0.877). Furthermore, compared with traditional TNM staging, our nomogram demonstrated greater accuracy in predicting patient outcomes. The risk stratification model derived from our prediction model may facilitate personalized treatment strategies for NPC patients. Our findings confirmed the prognostic significance of the PWR and PIV in NPC. High PIV levels (>363.47) and low PWR (≤36.42) values are associated with worse OS in NPC patients.

Targeting Glutamine Metabolism through Glutaminase Inhibition Suppresses Cell Proliferation and Progression in Nasopharyngeal Carcinoma.

Glutaminase (GLS), the key enzyme involved in glutamine metabolism, has been identified as a critical player in tumor growth and progression. The GLS inhibitor CB-839 has entered several clinical trials against a variety of tumors. Our study aimed to investigate the role and underlying mechanism of GLS and its inhibitor CB-839 in nasopharyngeal carcinoma (NPC). The expression, downstream genes, and signaling pathways of GLS in NPC were determined by real-time polymerase chain reaction (RT-PCR), PCR array, western blotting (WB), and immunohistochemical staining (IHC), and the phenotype of GLS was confirmed by in vivo experiments of subcutaneous tumor formation in mice and in vitro experiments of functional biology, including Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell migration, and Boyden invasion assay. Finally, it was also verified whether the treatment of NPC cells by GLS inhibitor CB-839 can change various biological functions and protein expression to achieve the purpose of blocking tumor progression. GLS was remarkably overexpressed in NPC cells and tissues, predicting a poor overall survival of NPC patients. GLS promoted cell cycle, proliferation, colony formation, migratory, and invasive capacities by regulating Cyclin D2 (CCND2) via PI3K/AKT/mTOR pathway in NPC in vitro and in vivo. Notably, CB-839 showed an effective anti-NPC tumor effect by blocking the biological functions of the tumor. The first innovative proof is that GLS promotes cell proliferation by regulating CCND2 via PI3K/AKT/mTOR pathway in NPC, and GLS inhibitor CB-839 may serve as a new potential therapeutic target for NPC treatment.

Prognostic significance of the novel nutrition-inflammation marker of lymphocyte-C-reactive protein ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy.

Recent studies indicate that the novel lymphocyte-C-reactive protein ratio (LCR) is strongly associated with the survival of various tumors, but its prognostic value in nasopharyngeal carcinoma (NPC) is understudied. This study aimed to explore the relationship between LCR and overall survival (OS) in NPC and develop a predictive model. A total of 841 NPC patients who received concurrent chemoradiotherapy (CCRT) between January 2010 and December 2014 were retrospectively enrolled and randomly divided into a training cohort (n = 589) and a validation cohort (n = 252), and 122 patients between January 2015 and March 2015 were included as an additional validation cohort. Univariate and multivariate Cox analyses were performed to identify variables associated with OS and construct a predictive nomogram. The predictive accuracy of the nomogram was evaluated and independently validated. The LCR score differentiated NPC patients into two groups with distinct prognoses (HR = 0.53; 95% CI: 0.32-0.89, P = 0.014). Multivariate analysis showed that age, T stage, N stage, EBV-DNA status, and LCR score were independently associated with OS, and a predictive nomogram was developed. The nomogram had a good performance for the prediction of OS [C-index = 0.770 (95% CI: 0.675-0.864)]. and outperformed the traditional staging system [C-index = 0.589 (95% CI: 0.385-0.792)]. The results were internally and additionally validated using independent cohorts. The pretreatment LCR could independently predict the overall survival in NPC patients. A novel LCR-based prognostic model of an easy-to-use nomogram was established, and it outperformed the conventional staging system in terms of predictive power. Further external verification remains necessary.

Prognostic Value of Serum Transferrin Level before Radiotherapy on Radio-Sensitivity and Survival in Patients with Nasopharyngeal Carcinoma.

To investigate the prognostic value of serum transferrin (TRF) level before intensity-modulated radiation therapy (IMRT) on radio-sensitivity and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). From October 2012 to October 2016, a total of 348 patients with NPC in the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed in our study. The concentration of serum TRF was detected by the method of enzyme-linked immunosorbent assay (ELISA). In the whole group, 46 patients received IMRT, and 302 patients received IMRT plus chemotherapy. The radio-sensitive tumor was defined when the local tumor lesions disappeared completely in the nasopharyngeal MRI scan and no tumor residues were found under the electronic nasopharyngoscope one month after the end of radiotherapy. The serum TRF level before IMRT was (1.34-3.89) g/L, with a median of 2.16 g/L and a mean of (2.20 ± 0.42) g/L. In the whole group, 242 cases (69.5%) were radiosensitive, and 106 cases (30.5%) were insensitive. The number of radiosensitive patients in the group of HTRF (transferrin > 2.16 g/L) and LTRF (transferrin ≤ 2.16 g/L) before radiotherapy was 129 (74.6%) and 113 (64.6%), respectively. The difference in radio-sensitivity between the two groups was statistically significant (χ2 = 4.103, p = 0.043). Logistic regression analysis showed that the level of TRF before radiotherapy (OR = 1.702; 95% CI 1.044~2.775; p = 0.033) was an independent factor for radio-sensitivity. The log-rank test showed that patients in the LTRF group achieved a significantly worse OS (χ2 = 5.388, p = 0.02) than those in the HTRF group. Cox regression analysis showed that baseline TRF level (HR = 1.706; 95% CI 1.065~2.731; p = 0.026) was an independent prognostic factor for overall survival. The low level of TRF before IMRT is a risk factor for radio-sensitivity and a prognostic factor for poor OS in NPC patients. It may be a promising marker to predict radio-sensitivity and OS in NPC patients who accept IMRT.

Retrospective analysis of Porphyromonas gingivalis in patients with nasopharyngeal carcinoma in central China.

Little is known about the presence and possible role of Porphyromonas gingivalis (P. gingivalis) in nasopharyngeal carcinoma (NPC), its co-infection with Epstein-Barr virus (EBV), or their association with clinical characteristics of patients with NPC in Central China, where NPC is non-endemic. A total of 45 NPC formalin-fixed paraffin-embedded (FFPE) tissues were retrospectively analyzed using immunohistochemistry (IHC) and a nested PCR combined with DNA sequencing to detect the presence of P. gingivalis, and using reverse transcription-quantitative PCR to detect the presence of EBV. Clinical data including EBV and P. gingivalis status were associated with overall survival (OS). All tumors were undifferentiated, non-keratinizing carcinomas, of which 40/45 (88.9%) were positive for EBV (EBV+), 26/45 (57.8%) were positive for P. gingivalis (by IHC), and 7/45 (15.6%) were positive for P. gingivalis DNA (P. gingivalis +). All seven P. gingivalis DNA-positive NPCs were co-infected with EBV. The 5-year survival rates of the patients with EBV-/P. gingivalis -, EBV+/P. gingivalis -, and EBV+/P. gingivalis + tumors were 60.0% (3/5), 39.4% (13/33) and 42.9% (3/7), respectively. No significant difference was found between the OS of NPC patients among the different infection groups (P=0.793). In conclusion, to the best of our knowledge, this is the first study to describe and confirm the presence of P. gingivalis in FFPE tissues from patients with NPC. P. gingivalis was found to co-exist with EBV in NPC tumor tissues, but is not etiologically relevant to NPC in non-endemic areas, such as Central China.

Prognostic value of MR-detected mandibular nerve involvement: potential indication for future individual induction chemotherapy in T4 nasopharyngeal carcinoma

PurposeTo investigate the prognostic significance of MR-detected mandibular nerve involvement (MNI) and its value for induction chemotherapy (IC) administration in patients with nasopharyngeal carcinoma (NPC) and T4 disease.MethodsThis retrospective study enrolled 792 non-metastatic, biopsy-proven NPC patients. Univariate and multivariate analysis were used to evaluate potential prognosticators. The inter-observer agreement was assessed by the kappa values.ResultsMR-detected MNI was observed in 141 (72.3%) patients among 195 patients with T4 disease, with excellent agreement between the readers (kappa = 0.926). Patients with MR-detected MNI presented better 5-year overall survival (OS) (hazard ratio [HR], 0.40; P = 0.006) than those with MR-negative MNI. Of these patients, IC treatment was verified as an independent factor (HR: 0.35; P = 0.014) with preferable effect on OS.ConclusionMR-detected MNI could serve as an independent favorable prognostic predictor for OS in NPC patients with stage T4, which should be considered for stratifying these patients for IC administration.

Knockdown of Annexin A2 Enhances Radiosensitivity by Increasing G2/M-Phase Arrest, Apoptosis and Activating the p38 MAPK-HSP27 Pathway in Nasopharyngeal Carcinoma.

Annexin A2 (ANXA2) has been found to be involved in cancer proliferation, metastasis and prognosis; however, its exact role in nasopharyngeal carcinoma (NPC) radioresistance remains unknown. We found that ANXA2 expression was correlated with prognosis in NPC patients, and longer overall survival in NPC patients with low ANXA2 expression than those with high ANXA2 expression. ANXA2 knockdown increased the radiosensitivity in radioresistant NPC cells, and ANXA2 overexpression decreased the radiosensitivity in NPC cells. Knocking-down ANXA2 expression increased the irradiation-induced apoptosis of radioresistant NPC cells, and ANXA2 overexpression decreased the irradiation-induced apoptosis of NPC cells. ANXA2 knockdown induced G2/M phase arrest in NPC cells post-irradiation, and ANXA2 overexpression abrogated G2/M phase arrest in NPC cells post-irradiation. ANXA2 overexpression resulted in inhibition of the p38 MAPK-HSP27 pathway, while ANXA2 knockdown resulted in activation of the p38 MAPK-HSP27 pathway. In addition, ANXA2 knockdown increased the radiosensitivity of the xenografted tumors in nude mice. Our data demonstrate that knockdown of Annexin A2 enhanced radiosensitivity in NPC by increasing G2/M-phase arrest, apoptosis and activating the p38 MAPK-HSP27 pathway. ANXA2 may be a promising target used to overcome radioresistance in NPC.

Exosomal miR-205-5p enhances angiogenesis and nasopharyngeal carcinoma metastasis by targeting desmocollin-2

The aim of this study was to investigate whether and how exosomal miR-205-5p regulated angiogenesis and nasopharyngeal carcinoma (NPC) metastasis. We found that up-regulated serum exosomal miR-205-5p levels were associated with NPC progression and worse overall survival of NPC patients. miR-205-5p over-expression significantly increased tube formation, wound healing, migration and invasion of NPC cells, and lung metastasis of NPC tumors, whereas miR-205-5p inhibition had opposite effects. Exosomal miR-205-5p from NPC cells promoted the migration, tube formation, and microvessel density (MVD) of HUVECs in vitro and in vivo. Furthermore, bioinformatics-, luciferase reporter-, and biotinylated miR-205-5p-based pull-down assays indicated that miR-205-5p directly bound to the 3′ UTR of desmocollin-2 (DSC2). Exosomal miR-205-5p targeted DSC2 to enhance the EGFR/ERK signaling and MMP2/MMP9 expression, promoting angiogenesis and NPC metastasis, which was abrogated by DSC2 over-expression. Finally, the levels of miR-205-5p transcripts were positively correlated with MVD but negatively with DSC2 expression in NPC tissues, and patients with miR-205high/DSC2low NPC had worse overall survival. In conclusion, exosomal miR-205-5p promotes angiogenesis and NPC metastasis by targeting DSC2 to enhance EGFR/ERK signaling and MMP expression. This exosomal/miR-205-5p/EGFR/ERK axis may be a new therapeutic target for intervention of NPC metastasis.

Prognostic value of EGFR and p-EGFR in nasopharyngeal carcinoma: A systematic review and meta-analysis.

Purpose:To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.Methods:A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).Results:A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I2 = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I2 = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).Conclusion:In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.Ethics and dissemination:This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.INPLASY registration number:INPLASY 202150010

Development and validation of a risk prediction score for patients with nasopharyngeal carcinoma

BackgroundWe aimed to develop and validate a predictive model for the overall survival (OS) of patients with nasopharyngeal carcinoma (NPC).MethodsOverall, 519 patients were retrospectively reviewed in this study. In addition, a random forest model was used to identify significant prognostic factors for OS among NPC patients. Then, calibration plot and concordance index (C-index) were utilized to evaluate the predictive accuracy of the nomogram model.ResultsWe used a random forest model to select the three most important features, dNLR, HGB and EBV DNA, which were significantly associated with the OS of NPC patients. Furthermore, the C-index of our model for OS were 0.733 (95% CI 0.673 ~ 0.793) and 0.772 (95% CI 0.691 ~ 0.853) in the two cohorts, which was significantly higher than that of the TNM stage, treatment, and EBV DNA. Based on the model risk score, patients were divided into two groups, associated with low-risk and high-risk. Kaplan–Meier curves demonstrated that the two subgroups were significantly associated with OS in the primary cohort, as well as in the validation cohort. The nomogram for OS was established using the risk score, TNM stage and EBV DNA in the two cohorts. The nomogram achieved a higher C-index of 0.783 (95% CI 0.730 ~ 0.836) than that of the risk score model 0.733 (95% CI 0.673 ~ 0.793) in the primary cohort (P = 0.005).ConclusionsThe established risk score model and nomogram resulted in more accurate prognostic prediction for individual patient with NPC.

Expression of ANCR in nasopharyngeal carcinoma patients and its clinical significance.

Anti-differentiation non-coding RNA (ANCR), a long non-coding RNA, is involved in the development, progression and metastasis of various human cancers. However, its clinical significance in nasopharyngeal carcinoma (NPC) still remains unknown. This study aimed to investigate ANCR expression and its clinical significance in NPC.Totally, 96 NPC tissues and 24 non-cancerous nasopharyngeal mucosa tissues were used. The levels of ANCR were determined by qRT-PCR. Relationship of ANCR with patient clinical characteristics, disease-free survival and overall survival (OS) was evaluated.ANCR expression was increased in NPC tissues compared to non-cancerous nasopharyngeal mucosae. ANCR expression was significantly related to lymph node metastasis, clinical stage, and tumor differentiation (P < .05). Kaplan-Meier survival analysis revealed that high level of ANCR expression was significantly associated with poor disease-free survival but not with OS in NPC patients. Univariate analysis showed a significant association between increased ANCR expression and adverse OS (P < .05), but multivariate analysis suggested that ANCR could not be used as an independent prognostic factor for NPC patients.ANCR is involved in the development and progression of NPC, but whether it can be used as an effective therapeutic target for NPC needs further study.

A novel prognostic model predicts overall survival in patients with nasopharyngeal carcinoma based on clinical features and blood biomarkers.

This study aims to develop and validate a novel prognostic model to estimate overall survival (OS) in nasopharyngeal carcinoma (NPC) patients based on clinical features and blood biomarkers. We assessed the model's incremental value to the TNM staging system, clinical treatment, and Epstein‐Barr virus (EBV) DNA copy number for individual OS estimation. We retrospectively analyzed 519 consecutive patients with NPC. A prognostic model was generated using the Lasso regression model in the training cohort. Then we compared the predictive accuracy of the novel prognostic model with TNM staging, clinical treatment, and EBV DNA copy number using concordance index (C‐index), time‐dependent ROC (tdROC), and decision curve analysis (DCA). Subsequently, we built a nomogram for OS incorporating the prognostic model, TNM staging, and clinical treatment. Finally, we stratified patients into high‐risk and low‐risk groups according to the model risk score, and we analyzed the survival time of these two groups using Kaplan–Meier survival plots. All results were validated in the independent validation cohort. Using the Lasso regression, we established a prognostic model consisting of 13 variables with respect to patient prognosis. The C‐index, tdROC, and DCA showed that the prognostic model had good predictive accuracy and discriminatory power in the training cohort than did TNM staging, clinical treatment, and EBV DNA copy number. Nomogram consisting of the prognostic model, TNM staging, clinical treatment, and EBV DNA copy number showed some superior net benefit. Based on the model risk score, we split the patients into two subgroups: low‐risk (risk score ≤ −1.423) and high‐risk (risk score > −1.423). There were significant differences in OS between the two subgroups of patients. Similar results were observed in the validation cohort. The proposed novel prognostic model based on clinical features and serological markers may represent a promising tool for estimating OS in NPC patients.

Downregulation of adipose triglyceride lipase by EB viral-encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is one of the most common human cancers in South-East Asia exhibiting typical features of lipid accumulation. EBV-encoded latent membrane protein 2A (LMP2A) is expressed in most NPCs enhancing migration and invasion. We recently showed an increased accumulation of lipid droplets in NPC, compared with normal nasopharyngeal epithelium. It is important to uncover the mechanism behind this lipid metabolic shift to better understand the pathogenesis of NPC and provide potential therapeutic targets. We show that LMP2A increased lipid accumulation in NPC cells. LMP2A could block lipid degradation by downregulating the lipolytic gene adipose triglycerol lipase (ATGL). This is in contrast to lipid accumulation due to enhanced lipid biosynthesis seen in many cancers. Suppression of ATGL resulted in enhanced migration invitro, and ATGL was found downregulated in NPC biopsies. The reduced expression level of ATGL correlated with poor overall survival in NPC patients. Our findings reveal a new role of LMP2A in lipid metabolism, correlating with NPC patient survival depending on ATGL downregulation.

Acylglycerol kinase promotes the stemness of nasopharyngeal carcinoma cells by promoting β-catenin translocation to the nucleus through activating PI3K/Akt pathway.

Recent evidences show that acylglycerol kinase (AGK) expression is related to the occurrence and development of various human cancers. However, its roles in nasopharyngeal carcinoma (NPC) progression are still unclear. This work aims to explore the roles of AGK in NPC cell stemness. It was shown that AGK expression was higher in NPC tissues compared to the adjacent tissues. Online dataset analysis revealed that AGK expression was negatively correlated with the overall survival of NPC patients. Gain and loss of functional experiments demonstrated that AGK positively regulated the stemness of NPC cells, as evident by the change of the tumor sphere-formation ability, ALDH1 activity and expression of stemness critical regulators. KEGG analysis were performed to determine the potential pathways of AGK involved in NPC cell stemness and showed that the PI3K/Akt pathway exhibited the most correlation with AGK expression. Further mechanistic studies confirmed that AGK promoted the stemness of NPC cells through activating the PI3K/Akt pathway, and thus enhancing β-catenin accumulation in nucleus. This study demonstrates a novel AGK/PI3K/Akt/β-catenin axis involving in NPC cell stemness.

MicroRNA-93, upregulated in serum of nasopharyngeal carcinoma patients, promotes tumor cell proliferation by targeting PDCD4.

Deregulation of microRNAs (miRs) has been demonstrated to contribute to the development and malignant progression of nasopharyngeal carcinoma (NPC). Recently, miR-93 was reported to be significantly upregulated in NPC tissues and cell lines, and promote the proliferation, migration and invasion of NPC cells in vitro, as well as tumor growth in vivo. However, whether there is any clinical value of serum miR-93 expression in NPC still remains unclear. Therefore, the present study aimed to explore the clinical significance of serum miR-93 expression in NPC. A total of 85 serum samples from NPC patients and 30 from healthy controls were collected. Reverse transcription-quantitative polymerase chain reaction data demonstrated that the serum expression of miR-93 was significantly increased in NPC patients, when compared with those in healthy controls. Following receiving chemo-radiotherapy, the serum miR-93 levels were significantly decreased in NPC patients. Furthermore, the increased serum levels of miR-93 were significantly associated with advanced grade, clinical stage, lymph node metastasis, as well as worse 5-year overall survival of NPC patients. Furthermore, the serum miR-93 expression was demonstrated to be an independent factor for predicating the prognosis of NPC. In vitro experiments demonstrated that knockdown of miR-93 caused a decrease in NPC cell proliferation, whereas overexpression of miR-93 promoted NPC cell proliferation. PDCD4 was then identified as a direct target of miR-93 in NPC cells. Overexpression of PDCD4 significantly eliminated the promoting effects of miR-93 overexpression on NPC cell proliferation. Taken together, these findings suggest that the serum miR-93 expression could be used as a predicator for the clinical outcome of NPC patients, and suggest that miR-93 may also become a potential therapeutic target for NPC treatment.

Targeting fatty acid synthase sensitizes human nasopharyngeal carcinoma cells to radiation via downregulating frizzled class receptor 10.

Objective: Our aim was to test the hypothesis that fatty acid synthase (FASN) expression contributes to radioresistance of nasopharyngeal carcinoma (NPC) cells and that inhibiting FASN enhances radiosensitivity.Methods: Targeting FASN using epigallocatechin gallate (EGCG) or RNA interference in NPC cell lines that overexpress endogenous FASN was performed to determine their effects on cellular response to radiation in vitro using MTT and colony formation assays, and in vivo using xenograft animal models. Western blot, immunohistochemistry, real-time PCR arrays, and real-time RT-PCR were used to determine the relationship between FASN and frizzled class receptor 10 (FZD10) expression. FZD10 knockdown and overexpression were used to determine its role in mediating FASN function in cellular response to radiation. Immunohistochemical staining was used to determine FASN and FZD10 expressions in human NPC tissues, followed by analysis of their association with the overall survival of patients.Results: FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells, both in vitro and in vivo. There was a positive association between FASN and FZD10 expression in NPC cell lines grown as monolayers or xenografts, as well as human tissues. FASN knockdown reduced FZD10 expression, and rescue of FZD10 expression abolished FASN knockdown-induced enhancement of radiosensitivity. FASN and FZD10 were both negatively associated with overall survival of NPC patients.Conclusions: FASN contributes to radioresistance, possibly via FZD10 in NPC cells. Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients. EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs.