Pretreatment platelet count improves the prognostic performance of the TNM staging system and aids in planning therapeutic regimens for nasopharyngeal carcinoma:a singleinstitutional study of 2,626 patients

Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer.This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma(NPC).Methods:A total of 2,626 patients with NPC were retrospectively analyzed.Platelet count >300 × 10~9/L was defined as thrombocytosis.Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy.Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overall survival(OS)[hazard ratio(HR) = 1.810,95%confidence interval(CI) = 1.531-2.140,P < 0.001]and distant metastasis-free survival(DMFS)(HR = 1.873,95%CI = 1.475-2.379,P < 0.001) in the entire patient cohort.Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category,N category,or TNM classification(all P < 0.001).Receiver operating characteristic(ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count(P = 0.030).Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis(HR = 0.416,95%CI = 0.226-0.765,P = 0.005).Conclusions:Pretreatment platelet count,when combined with TNM classification,is a useful indicator for metastasis and survival in patients with NPC.It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.

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

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

ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin-3 and NRXN3

Background:Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma(NPC).However,the epigenetic mechanisms underlying NPC metastasis remains poorly understood.We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment.Methods:Bisulfite pyrosequencing was used to analyze zinc finger protein 582(ZNF582)methylation in NPC tissues and cell lines.Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting were used to determine the expression of ZNF582.In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC.ZNF582-targeting genes were identified by chromatin immunoprecipitation sequencing(ChIP-seq)and were confirmed by ChIP-qPCR and luciferase assay.Results:ZNF582 promoter was hypermethylated in NPC,and both the mRNA and protein levels of ZNF582 were down-regulated in NPC tissues and cell lines.The restoration of ZNF582 inhibited NPC migration,invasion,and metastasis,while the knockdown of ZNF582 promoted NPC migration,invasion,and metastasis in vitro and in vivo.ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin-3 and NRXN3.Both Nectin-3 and NRXN3 were identified as functional targets of ZNF582,and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis.Conclusions:ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin-3 and NRXN3,which may provide novel therapeutic targets for NPC treatment.

Low-dose metronomic chemotherapy improves tumor control in nasopharyngeal carcinoma

1 BACKGROUND Nasopharyngeal carcinoma(NPC)is a unique head and neck malignancy prevalent in East Asia[1].It is highly malignant,with the non-keratinizing pathological subtype constituting approximately 95%of NPC cases in endemic areas.Chemotherapy in combination with radiotherapy is recommended for locoregionally advanced NPC(LANPC),especially in subgroups at higher risk of distant metastasis(e.g.,N2-3 vs.N0-1 diseases,high vs.low plasma Epstein-Barr virus[EBV]DNA copy number)[2,3].Concurrent chemoradiotherapy with or without induction chemotherapy is considered the backbone of the current chemoradiotherapy strategies for NPC[2,3].Nevertheless,although complete clinical remission could be achieved in more than 90%of patients after definitive chemoradiotherapy,about 20%-30%of patients will have disease recurrence subsequently[4,5],which might be caused minimal residual disease(MRD),either at locoregional or distant sites[6,7].Thus,adjuvant therapy is needed to improve tumor control.

Correction to: ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin-3 and NRXN3

Following publication of this article[1],the authors noticed that the mismatched images were inadvertently included in Figure 5(migration assays of SUNE1-shNRXN3-#2 group in Figure 5I)and Figure 6(invasion assays of SUNE1-ZNF582+Nectin3 group in Figure 6A).This error has now been corrected online.