Prognosis Of Nasopharyngeal Carcinoma Research Articles

Deep learning based analysis of G3BP1 protein expression to predict the prognosis of nasopharyngeal carcinoma.

Ras-GTPase-activating protein (GAP)-binding protein 1 (G3BP1) emerges as a pivotal oncogenic gene across various malignancies, notably including nasopharyngeal carcinoma (NPC). The use of automated image analysis tools for immunohistochemical (IHC) staining of particular proteins is highly beneficial, as it could reduce the burden on pathologists. Interestingly, there have been no prior studies that have examined G3BP1 IHC staining using digital pathology. Whole-slide images (WSIs) were meticulously collected and annotated by experienced pathologists. A model was intricately designed and rigorously tested to yield the quantitative data regarding staining intensity and extent. The collective output data was subjected multiplicative analysis, exploring its correlation with the prognosis. The G3BP1 molecular marker scoring model was successfully established utilizing deep learning methodologies, with a calculated threshold staining scores of 1.5. Notably, patients with NPC exhibiting higher expression levels of G3BP1 proteins displayed significantly lower for overall survival rates (OS). Multivariate analysis further validated that positive expression of G3BP1 stood as an independent poorer prognostic factors, indicating a poorer prognosis for NPC patients. Computational pathology emerges as a transformative tool capable of substantially reducing the burden on pathologists while concurrently enhancing and diagnostic sensitivity and specificity. The positive expression of G3BP1 protein serves as valuable, independent biomarker, offering predictive insights into a poor prognosis for patients with NPC.

Systemic immune inflammation index combined with Epstein-Barr virus DNA for predicting the prognosis of nasopharyngeal carcinoma: A retrospective study.

Cancer has consistently been the leading cause of death worldwide, with head and neck cancer (HNC) being one of the top ten causes of cancer-related death. Nasopharyngeal carcinoma (NPC), in particular, is a cancer that is unique to East Asia. Numerous studies have shown that the Epstein-Barr virus (EBV) DNA load and the systemic immune inflammation (SII) index can serve as prognostic indicators for NPC patients. However, no studies have compared different predictive models of inflammatory factors. This study combines the SII and the EBV virus load in patients with stage I to IV NPC and compares different inflammatory factor models to determine the best predictive model. We reviewed 240 patients with stage I to IV NPC who were diagnosed between January 2016 and July 2023. We collected data from adult patients who were diagnosed with NPC and included those who completed the definitive staging workup and treatment in this analysis. We tested various inflammatory markers and the EBV DNA load via Cox regression for survival analysis. We found that the EBV viral load, the SII, and the SIRI are related to the severity of nasopharyngeal cancer. In the univariate Cox regression analysis, clinical stage, EBV virus load (HR: 2.15, 95% CI: 1.19-3.90), NLR (2.37, 1.29-4.34), PLR (2.7, 1.06-6.87), SIRI (2.02, 1.11-3.68), and SII (2.45, 1.251-4.89) were prognostic factors for overall survival. In the multivariate analysis, after adjusting for sex, age and clinical stage, a higher EBV virus load and SII were associated with a worse prognosis (HR: 4.71, 1.95-11.41). The combination of the EBV viral load and the SII was a better predictor of NPC prognosis.

GNA14 may be a potential prognostic biomarker in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a highly invasive malignant tumor. Recurrence and distant metastasis represent the primary causes of treatment failure. This study aimed to identify biomarkers highly associated with NPC and investigate its roles in tumor progression. Transcriptome sequencing (RNA-seq) data of NPC and normal tissues were downloaded from the Gene Expression Omnibus (GEO) database. By analyzing the RNA-seq data, we found that G Protein Subunit Alpha 14 (GNA14) is closely associated with the diagnosis and prognosis of NPC. Immunohistochemistry (IHC) was used to detect the expression of GNA14 in tumor tissues of 165 NPC patients, and we analyzed the relationship between GNA14 expression and patient prognosis. The potential mechanisms by which GNA14 affects tumor prognosis were preliminarily analyzed using bioinformatics analysis. Analysis of RNA-seq data and IHC showed that GNA14 expression was downregulated in NPC (p < 0.001, p < 0.01, respectively), and low expression of GNA14 was closely associated with poor prognosis. IHC analysis showed that patients with low GNA14 expression had significantly shorter progression-free survival (PFS) and distant metastasis-free survival (DMFS) than those with high GNA14 expression (p = 0.023, p = 0.008, respectively). Multivariate analysis indicated that the GNA14 expression was an independent risk factor for DMFS (p = 0.030). The DMFS nomogram included GNA14 expression, EBV DNA, and N stage as prognostic factors and the concordance index (C-index) of the nomogram was 0.73. Bioinformatics analysis indicated that NPC patients with low GNA14 expression might represent lower levels of immune cell infiltration and poorer drug sensitivity. Low GNA14 expression may be a risk factor for poor prognosis in NPC.

A prognostic nomogram for patients with III-IV nasopharyngeal carcinoma based on dynamic changes in the inflammatory and nutrition index.

The purpose of the study was to explore the value of dynamic changes in inflammatory and nutritional index after comprehensive treatment in patients with stage III-IVA nasopharyngeal carcinoma (NPC). A prognostic model was also established and validated for progression-free survival (PFS) of patients. We retrospectively selected 279 NPC patients with stage III-IVA. Their general clinical data and hematological index were collected and then calculated the changes during treatment. X-tile software was used to determine the optimal cut-off value. COX regression, Lasso method, and Boruta method were used to variable selection and model establishment. Using the bootstrap internal validation method, concordance index (C-index), calibration plot, and Kaplan-Meier curves were used to evaluate the model. To test the prognostic value of the model, we have also evaluated the performance of the nomogram against a conventional tumor metastasis staging system (TNM). Multivariable COX regression analysis demonstrated that clinical staging, delta lymphocyte, delta monocyte, delta albumin, delta platelet-to-lymphocyte ratio and delta systemic immune inflammation index were related to the PFS of NPC patients. The C-index of the model was 0.712, and the calibration curve indicated that the model had good consistency. The C-index of the TNM staging system was 0.597, which was considerably lower compared to our model (P = 0.015). We demonstrated the predictive value of dynamic changes in inflammatory and nutritional indices for the prognosis of NPC by successfully establishing and validating a prognostic model for predicting 1- and 3-year PFS after comprehensive treatment in patients with stage III-IVA NPC.

BRD7 enhances the radiosensitivity of nasopharyngeal carcinoma cells by negatively regulating USP5/METTL3 axis-mediated homologous recombination repair.

An important reason for the poor prognosis of nasopharyngeal carcinoma (NPC) patients is radioresistance. Our previous studies demonstrated that BRD7 is expressed at low levels in NPC and functions as a tumor suppressor to inhibit NPC progression and metastasis. However, the role and mechanism of BRD7 in the development of radioresistance in NPC cells remain unclear. In this study, we first found that BRD7 was lowly expressed in radioresistant NPC tissues and cells compared to radiosensitive tissues and cells and that overexpression of BRD7 promoted the induction of DNA double-strand breaks and increased radiosensitivity in NPC cells. Mechanistically, BRD7 competitively inhibits the binding of the deubiquitinating enzyme USP5 to METTL3, thereby reducing the protein stability of METTL3 through the ubiquitin-proteasome pathway. Furthermore, METTL3 was confirmed to suppress the induction of DSBs and promote the development of NPC radioresistance by regulating BRCA1- and RAD51-mediated homologous recombination repair. Moreover, high BRD7 expression and low METTL3 expression are positively correlated with radiosensitivity and good prognosis in NPC patients. Taken together, our findings reveal that BRD7 promotes the radiosensitization of NPC cells by negatively regulating USP5/METTL3 axis activity and indicate that targeting the BRD7/METTL3 axis might be a novel therapeutic strategy for NPC radiosensitization.

Impact of the radiotherapy rhythm on prognosis in nasopharyngeal carcinoma

Objective The role of chronoradiobiology in nasopharyngeal carcinoma (NPC) has not been fully elucidated. We sought to investigate the impact of radiotherapy rhythm on the survival outcomes of individuals to explore a chronomodulated radiation strategy to improve prognosis of NPC. Methods A cohort comprising non-metastatic NPC patients subjected to intensity-modulated radiotherapy at Fujian Cancer Hospital between Jan. 2016 and Dec. 2019 was assembled. Rhythmic fluctuation of radiotherapy (RFRT) was quantified based on the temporal distribution of radiation delivery. Cox proportional hazard model was performed to explore the impact of radiotherapy rhythm on all-cause mortality. The maximally selected rank statistics method was employed to discern an optimal cutoff. Sensitivity analyses were conducted to ensure the robustness of observed associations. Results Our analysis encompassed 2245 patients, with a median follow-up duration of 55 months, during which 315 individuals succumbed. Multivariate Cox regression analysis unveiled a significant correlation between prolonged RFRT and heightened mortality risk in NPC patients (HR, 1.17, 95% CI, 1.07-1.27, p < .001), a relationship robust to comprehensive adjustment for confounding variables. A cutoff value of 3 h was selected for potential clinical application, beyond which patients exhibited markedly poorer survival outcomes. Subgroup analyses consistently underscored the directional consistency of observed effects. Conclusion Our study sheds light on the potential advantages of scheduling radiotherapy sessions at consistent times. These findings have implications for optimizing radiotherapy schedules and warrant further investigation into personalized chronotherapy approaches in NPC management.

A novel proteomic prognostic signature characterizes the immune landscape and predicts nasopharyngeal carcinoma prognosis

BackgroundNasopharyngeal carcinoma (NPC) is a highly diverse and aggressive cancer type, leading to varying prognoses and responses to immunotherapy. This study aims to develop a protein-based signature that provides new insights into assessing the prognosis and immunotherapeutic response in NPC patients. Methods and ResultsWe obtained transcriptomic and proteomic data for NPC from TCGA and CPTAC databases, respectively. Differentially expressed proteins with prognostic significance were identified using limma combined with uniCox analysis. A prognostic protein signature was created utilizing the LASSO algorithm. Receiver operating characteristic (ROC) curve analysis along with Kaplan-Meier survival analysis was conducted to assess the predictive accuracy of this signature. To evaluate immune infiltration levels among patients categorized by high or low risk scores (RPscores), we employed ssGSEA and ESTIMATE methods, while TIDE was used to forecast responses to immunotherapy. Our research pinpointed four critical prognostic proteins: CdSTA, AGR3, DUSP14, and LRRC17, allowing us to compute risk scores (RPscores). Kaplan-Meier curves demonstrated that individuals in the low-risk category exhibited better survival rates. Furthermore, RPscore effectively predicted overall survival across both training and testing cohorts. The ssGSEA results indicated that RPscore is linked with an immune-suppressive microenvironment correlating with diminished immune responses. Notably, DUSP14 showed significant upregulation in NPC cases; its role in promoting cell invasion and metastasis was confirmed through in vitro studies. ConclusionWe have established a robust protein-related signature capable of accurately forecasting prognosis as well as immunotherapy outcomes for NPC patients. Moreover, DUSP14 emerged as a potential therapeutic target due to its strong association with patient prognosis in nasopharyngeal carcinoma.

A systematic review of the predictive value of radiomics for nasopharyngeal carcinoma prognosis.

Radiomics has been widely used in the study of tumours, which has predictive and prognostic value in nasopharyngeal carcinoma (NPC). Therefore, we collected relevant literature to explore the role of current radiomics in predicting the prognosis of NPC. We performed a systematic literature review and meta-analysis in accordance with the preferred reporting items in the systematic evaluation and meta-analysis guidelines. We included papers on radiomics published before May 5, 2024, to evaluate the predictive ability of radiomics for the prognosis of NPC. The methodological quality of the included articles was evaluated using the radiomics quality score. The area under the curve (AUC), combined sensitivity and combined specificity were used to evaluate the ability of radiomics models to predict the prognosis of NPC. A total of 20 studies met the inclusion criteria for the current systematic review, and 13 papers were included in the meta-analysis. The radiomics quality score ranged from 7 to 20 (maximum score: 36). The diagnostic test forest plots showed that the diagnostic OR of radiology was 11.04 (95% CI: 5.11-23.87), while the ORs for sensitivity and 1-specificity were 0.75 (95% CI: 0.73-0.78) and 0.74 (95% CI: 0.72-0.76), respectively. It cannot be determined whether the combined model was superior to the radiomics model for predicting the prognosis of NPC. It is unclear whether the fact that the radiomics model was composed of features extracted from MRI is due to CT. The AUC of PFS was larger than that of disease-free survival (P < .05). The overall AUC value is 0.8265. This study summarized all the studies that examined the predictive value of radiomics for NPC prognosis. Based on the summarized AUC values, as well as sensitivity and 1-specificity, it can be concluded that radiomics has good performance in predicting the prognosis of NPC. Radiomics models have certain advantages in predicting the effectiveness of PFS compared to predicting disease-free survival. It cannot be determined whether the combination model is superior to the radiomics model in predicting NPC prognosis, nor can it be determined whether imaging methods have differences in predictive ability. The findings confirmed and provided further evidence supporting the effectiveness of radiomics for the prediction of cancer prognosis.

Dual role of targeting NAE1 in nasopharyngeal carcinoma: Antitumor effects yet inducing radiotherapy resistance

Background and objectivesThe inhibitor MLN4924 of Neural Precursor Cell-Expressed Developmentally Down-Regulated 8 (NEDD8) Activating Enzyme 1 (NAE1) has been found to suppress the growth of nasopharyngeal carcinoma (NPC). However, its effect on NPC's radiotherapy sensitivity remains unclear. MethodsBy integrating single-cell RNA sequencing and bulk RNA sequencing, we predict the impact of NAE1 on the cell cycle, cell death, and its relationship with radiotherapy sensitivity and prognosis in NPC. The effect of inhibiting NAE1 on NPC cell behavior and radiation sensitivity is explored through MLN4924 intervention in vitro and in vivo. We construct a prognosis prediction model based on NAE1 using machine learning methods and validate the efficacy of NAE1 and the model in clinical cohorts. ResultsNPC patients with high NAE1 expression have better prognosis and higher expression in the radiotherapy-sensitive group. Inhibiting NAE1 with MLN4924 causes cell cycle arrest in NPC cells, preventing them from entering the G2/M phase, thereby inhibiting proliferation but not affecting migration and metastasis. However, in vitro and in vivo experiments demonstrate that inhibiting NAE1 with MLN4924 leads to increased resistance of NPC to radiation. ConclusionsTargeting NAE1 for NPC treatment may have dual effects, inhibiting NPC proliferation while also increasing radiation resistance.

LncRNA BC200 promotes the development of EBV-associated nasopharyngeal carcinoma by competitively binding to miR-6834-5p to upregulate TYMS expression

Nasopharyngeal carcinoma (NPC) is closely related to Epstein–Barr virus (EBV) infection. Long noncoding RNAs (lncRNAs) play important roles in cancers. However, the molecular mechanism underlying the roles of lncRNAs in EBV-associated NPC remains largely unclear. In this study, we confirmed that the expression of the lncRNA brain cytoplasmic 200 (BC200) was significantly increased in EBV-infected NPC cells and tissues. BC200 facilitated the growth and migration of NPC cells, suggesting that it participated in NPC progression by functioning as an oncogene. Mechanistically, BC200 was found to act as a ceRNA by sponging and inhibiting miR-6834-5p. Thymidylate synthetase (TYMS), whose high expression was reported to be an independent indicator of poor prognosis in NPC via an unknown mechanism, was identified as a target gene of miR-6834-5p in the present study. BC200 upregulated TYMS expression in a manner that depends on miR-6834-5p. TYMS was abnormally upregulated in EBV-positive NPC cells and tissues, and its ectopic expression contributed to the proliferation and migration of NPC cells. This study highlights the role of lncRNA BC200, which is upregulated by EBV, in promoting the development of NPC, suggesting that BC200-mediated ceRNA network may be valuable biomarkers for the diagnosis and treatment of EBV-associated NPC.

EIF4A3-Induced Upregulation of hsa_circ_0049396 Attenuates the Tumorigenesis of Nasopharyngeal Carcinoma by Regulating the Hippo-YAP Pathway.

Circular RNAs (circRNAs) and eukaryotic translation initiation factor 4A3 (EIF4A3) have been reported to participate in the pathogenesis of nasopharyngeal carcinoma (NPC), but their mechanism has not been fully understood. This research aimed to confirm the role and regulatory mechanism of hsa_circ_0049396 interacting with EIF4A3 in NPC tumorigenesis. Quantitative real time polymerase chain reaction (qRT-PCR) was executed to detect the levels of hsa_circ_0049396 and EIF4A3. Cell function experiments and nude mice xenograft assay were used to confirm the role of hsa_circ_0049396 in NPC. The regulatory effect of EIA4A3 on hsa_circ_0049396 was determined by circInteractome prediction, RNA binding protein immunoprecipitation (RIP) assay, and qRT-PCR. In addition, the Hippo-YAP pathway-related proteins and EIF4A3 protein were detected by western blotting. hsa_circ_0049396 was proved to be downregulated in NPC samples, and its low expression indicated the poor prognosis of NPC. After upregulating hsa_circ_0049396 in NPC cells, the proliferation, migration, invasion, and tumor growth invivo were suppressed by inhibiting the Hippo-YAP pathway. Moreover, EIF4A3 bound to the flanking regions of the hsa_circ_0049396 to enhance hsa_circ_0049396 expression in NPC cells. hsa_circ_0049396 mediated by EIF4A3 in NPC can attenuate NPC tumorigenesis by inhibiting the Hippo-YAP pathway. This finding may provide a potential early diagnostic biomarker or drug target to improve the precision medicine approaches of NPC.

Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma.

Homologous recombination deficiency (HRD) score is a reliable indicator of genomic instability. The significance of HRD in nasopharyngeal carcinoma (NPC), particularly its influence on prognosis and the immune microenvironment, has yet to be adequately explored. Understanding HRD status comprehensively can offer valuable insights for guiding precision treatment. We utilised three cohorts to investigate HRD status in NPC: the Zhujiang cohort from local collection and the Hong Kong (SRA288429) and Singapore (SRP035573) cohorts from public datasets. The GATK (genome analysis toolkit) best practice process was employed to investigate germline and somatic BRCA1/2 mutations and various bioinformatics tools and algorithms to examine the association between HRD status and clinical molecular characteristics. We found that individuals with a negative HRD status (no-HRD) exhibited a higher risk of recurrence [hazard ratio (HR), 1.43; 95% confidence interval (CI), 2.03-333.76; p = 0.012] in the Zhujiang cohort, whereas, in the Singapore cohort, they experienced a higher risk of mortality (HR, 26.04; 95% CI, 1.43-34.21; p = 0.016) compared with those in the HRD group. In vitro experiments demonstrated that NPC cells with BRCA1 knockdown exhibit heightened sensitivity to chemoradiotherapy. Furthermore, the HRD group showed significantly higher tumour mutational burden and tumour neoantigen burden levels than the no-HRD group. Immune infiltration analysis indicated that HRD tissues tend to have a non-inflamed tumour microenvironment. In conclusion, patients with HRD exhibit a comparatively favourable prognosis in NPC, possibly associated with a non-inflammatory immune microenvironment. These findings have positive implications for treatment stratification, enabling the selection of more precise and effective therapeutic approaches and aiding in the prediction of treatment response and prognosis to a certain extent.

Treatment-Related Lymphopenia is Possibly a Marker of Good Prognosis in Nasopharyngeal Carcinoma: a Propensity-Score Matching Analysis

Treatment-Related Lymphopenia is Possibly a Marker of Good Prognosis in Nasopharyngeal Carcinoma: a Propensity-Score Matching Analysis

Angiogenesis in nasopharyngeal carcinoma: insights, imaging, and therapeutic strategies.

Nasopharyngeal carcinoma (NPC) is a highly prevalent head and neck malignancy in southern China frequently diagnosed at advanced stages owing to subtle early symptoms and associated metastasis. Angiogenesis emerges as a pivotal factor in NPC progression, with numerous angiogenesis-related factors showing aberrant expression and contributing to increased neovascularization within NPC tumors. These abnormal vessels not only nourish tumor growth but also facilitate metastasis, culminating in unfavorable patient outcomes. Multiple studies have demonstrated the applicability of various imaging techniques for assessing angiogenesis in NPC tumors, thus serving as a foundation for personalized treatment strategies and prognostic assessments. Anti-angiogenic therapies have exhibited significant potential for inhibiting NPC angiogenesis and exerting anti-tumor effects. To enhance efficacy, anti-angiogenic drugs are frequently combined with other treatment modalities to synergistically enhance anti-tumor effects while mitigating the side effects associated with single-agent therapies, consequently improving patient prognosis. Identifying the potential mechanisms and key targets underlying NPC angiogenesis and exploring more effective detection and treatment approaches holds promise for shaping the future of NPC diagnosis, treatment, and prognosis, thereby offering new avenues and perspectives for research and clinical practice.

Novel prognostic biomarkers in nasopharyngeal carcinoma unveiled by mega-data bioinformatics analysis

Nasopharyngeal carcinoma (NPC) is commonly diagnosed at an advanced stage with a high incidence rate in Southeast Asia and Southeast China. However, the limited availability of NPC patient survival data in public databases has resulted in less rigorous studies examining the prediction of NPC survival through construction of Kaplan-Meier curves. These studies have primarily relied on small samples of NPC patients with progression-free survival (PFS) information or data from head and neck squamous cell carcinoma (HNSCC) studies almost without NPC patients. Thus, we coanalyzed RNA expression profiles in eleven datasets (46 normal (control) vs 160 tumor (NPC)) downloaded from the Gene Expression Omnibus (GEO) database and survival data provided by Jun Ma from Sun Yat-sen University. Then, differential analysis, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and network analysis were performed using STRING database. After that, 2142 upregulated differentially expressed genes (DEGs) and 3857 downregulated DEGs were screened. Twenty-five of them were identified as hub genes, which were enriched in several pathways (cilium movement, extracellular matrix structural constituent, homologous recombination and cell cycle). Utilizing the comprehensive dataset we amassed from GEO database, we conducted a survival analysis of DEGs and subsequently constructed survival models. Seven DEGs (RASGRP2, MOCOS, TTC9, ARHGAP4, DPM3, CD37, and CD72) were identified and closely related to the survival prognosis of NPC. Finally, qRT-PCR, WB and IHC were performed to confirm the elevated expression of RASGRP2 and the decreased expression of TTC9, CD37, DPM3 and ARHGAP4, consistent with the DEG analysis. Conclusively, our findings provide insights into the novel prognostic biomarkers of NPC by mega-data bioinformatics analysis, which suggests that they may serve special targets in the treatment of NPC.

MiR-122-5p regulates erastin-induced ferroptosis via CS in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a tumor that occurs in the nasopharynx. Although advances in detection and treatment have improved the prognosis of NPC the treatment of advanced NPC remains challenging. Here, we explored the effect of microRNA (miR)-122-5p on erastin-induced ferroptosis in NPC cells and the role of ferroptosis in the development of NPC. The effect of miR-122-5p silencing and overexpression and the effect of citrate synthase on erastin-induced lipid peroxidation in NPC cells was analyzed by measuring the amounts of malondialdehyde, Fe2+, glutathione, and reactive oxygen species and the morphological alterations of mitochondria. The malignant biological behavior of NPC cells was examined by cell counting kit-8, EDU, colony formation, Transwell, and wound healing assays. The effects of miR-122-5p on cell proliferation and migration associated with ferroptosis were examined in vivo in a mouse model of NPC generated by subcutaneous injection of NPC cells. We found that erastin induced ferroptosis in NPC cells. miR-122-5p overexpression inhibited CS, thereby promoting erastin-induced ferroptosis in NPC cells and decreasing NPC cell proliferation, migration, and invasion.

Radiomics-based lymph nodes prognostic models from three MRI regions in nasopharyngeal carcinoma

Accurate prediction of the prognosis of nasopharyngeal carcinoma (NPC) is important for treatment. Lymph nodes metastasis is an important predictor for distant failure and regional recurrence in patients with NPC. Traditionally, subjective radiological evaluation increases concerns regarding the accuracy and consistency of predictions. Radiomics is an objective and quantitative evaluation algorithm for medical images. This retrospective analysis was conducted based on the data of 729 patients newly diagnosed with NPC without distant metastases to evaluate the performance of radiomics pretreatment using magnetic resonance imaging (MRI)-determined metastatic lymph nodes models to predict NPC prognosis with three delineation methods. Radiomics features were extracted from all lymph nodes (ALN), largest lymph node (LLN), and largest slice of the largest lymph node (LSLN) to generate three radiomics signatures. The radiomics signatures, clinical model, and radiomics-clinic merged models were developed in training cohort for predicting overall survival (OS). The results showed that LSLN signature with clinical factors predicted OS with high accuracy and robustness using pretreatment MR-determined metastatic lymph nodes (C-index [95 % confidence interval]: 0.762[0.760–0.763]), providing a new tool for treatment planning in NPC.

Combined pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts survival and prognosis in patients with non-metastatic nasopharyngeal carcinoma: a retrospective study

The clinical significance of the combination of neutrophil–lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.

PICK1 inhibits the malignancy of nasopharyngeal carcinoma and serves as a novel prognostic marker

Although many important advances have been made in the treatment of nasopharyngeal carcinoma (NPC) in recent years, local recurrence and distant metastasis remain the main factors affecting NPC prognosis. Biomarkers for predicting the prognosis of NPC need to be urgently identified. Here, we used whole-exon sequencing (WES) to determine whether PICK1 mutations are associated with the prognosis of NPC. Functionally, PICK1 inhibits the proliferation and metastasis of NPC cells both in vivo and in vitro. Mechanistically, PICK1 inhibited the expression of proteins related to the Wnt/β-catenin signaling pathway. PICK1 restrained the nuclear accumulation of β-catenin and accelerated the degradation of β-catenin through the ubiquitin-proteasome pathway. The reduced PICK1 levels were significantly associated with poor patient prognosis. Hence, our study findings reveal the mechanism by which PICK1 inactivates the Wnt/β-catenin signaling pathway, thereby inhibiting the progression of NPC. They support PICK1 as a potential tumor suppressor and prognostic marker for NPC.

High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma.

Protein phosphatase 1 catalytic subunit gamma (PPP1CC) promotes DNA repair and tumor development and progression, however, its underlying mechanisms remain unclear. This study investigated the molecular mechanism of PPP1CC's involvement in DNA repair and the potential clinical implications. High expression of PPP1CC was significantly correlated with radioresistance and poor prognosis in human nasopharyngeal carcinoma (NPC) patients. The mechanistic study revealed that PPP1CC bound to Ku70/Ku80 heterodimers and activated DNA-PKcs by promoting DNA-PK holoenzyme formation, which enhanced nonhomologous end junction (NHEJ) -mediated DNA repair and led to radioresistance. Importantly, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) interacted with PPP1CC to enhance its stability by removing the K48-linked polyubiquitin chain at Lys234 to prevent PPP1CC degradation. Therefore, BRCC3 helped the overexpressed PPP1CC to maintain its high protein level, thereby sustaining the elevation of DNA repair capacity and radioresistance. Our study identified the molecular mechanism by which PPP1CC promotes NHEJ-mediated DNA repair and radioresistance, suggesting that the BRCC3-PPP1CC-Ku70 axis is a potential therapeutic target to improve the efficacy of radiotherapy.