The effect of socioeconomic factors on receipt of definitive treatment and survival outcomes in non‐metastatic head and neck squamous cell carcinoma (HNSCC) remains unclear. Eligible patients (n = 37 ...995) were identified from the United States Surveillance, Epidemiology and End Results (SEER) database between 2007 and 2012. Socioeconomic factors (i.e., median household income, education level, unemployment rate, insurance status, marital status and residence) were included in univariate/multivariate Cox regression analysis; validated factors were used to generate nomograms for cause‐specific survival (CSS) and overall survival (OS), and a prognostic score model for risk stratification. Low‐ and high‐risk groups were compared for all cancer subsites. Impact of race/ethnicity on survival was investigated in each risk group. Marital status, median household income and insurance status were included in the nomograms for CSS and OS, which had higher c‐indexes than the 6th edition TNM staging system (all P < 0.001). Based on three disadvantageous socioeconomic factors (i.e., unmarried status, uninsured status, median household income <US $65 394), the prognostic score model generated four risk subgroups with scores of 0, 1, 2 or 3, which had significantly separated CSS/OS curves (all P < 0.001). Low‐risk patients (score 0–1) were more likely to receive definitive treatment and obtain better CSS/OS than high‐risk patients (score 2–3). Chinese and non‐Hispanic black patients with high‐risk socioeconomic status had best and poorest CSS/OS, respectively. Therefore, marital status, median household income and insurance status have significance for predicting survival outcomes. Low‐risk socioeconomic status and Chinese race/ethnicity confer protective effects in HNSCC.
We built nomograms for CSS/OS and a prognostic score model for risk stratification based on validated socioeconomic factors, such as marital status, median household income and insurance status. Both nomograms had higher efficacies than the 6th edition TNM staging system, and the prognostic score model generated four risk subgroups with separated CSS/OS. Low‐risk socioeconomic status and Chinese race/ethnicity confer protective effects on patients with non‐matastatic HNSCC.
The optimal post-treatment surveillance strategy that can detect early recurrence of a cancer within limited visits remains unexplored. Here we adopt nasopharyngeal carcinoma as the study model to ...establish an approach to surveillance that balances the effectiveness of disease detection versus costs. A total of 7,043 newly-diagnosed patients are grouped according to a clinic-molecular risk grouping system. We use a random survival forest model to simulate the monthly probability of disease recurrence, and thereby establish risk-based surveillance arrangements that can maximize the efficacy of recurrence detection per visit. Markov decision-analytic models further validate that the risk-based surveillance outperforms the control strategies and is the most cost-effective. These results are confirmed in an external validation cohort. Finally, we recommend the risk-based surveillance arrangement which requires 10, 11, 13 and 14 visits for group I to IV. Our surveillance strategies might pave the way for individualized and economic surveillance for cancer survivors.
Epstein–Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA‐IgA) and viral capsid antigen (VCA‐IgA) are the most commonly used ...to screen for NPC in endemic areas. However, the prognostic value of serum EA‐IgA and VCA‐IgA in patients with NPC is less clear. We hypothesize that serum EA‐IgA and VCA‐IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non‐metastatic NPC and undetectable pEBV DNA were included. Serum EA‐IgA and VCA‐IgA were determined by ELISA. After analysis, serum EA‐IgA and VCA‐IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA‐IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA‐IgA >1:120 had significantly inferior 5‐year progression‐free survival (80.4% vs 89.6%, P = 0.025), distant metastasis‐free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse‐free survival (88.4% vs 95.6%, P = 0.023; log–rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA‐IgA became insignificant. Further analyses revealed that serum VCA‐IgA was not an independent prognostic factor in early N (N0–1) or advanced N (N2–3) stage NPC. In summary, although both EA‐IgA and VCA‐IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.
To the best of our knowledge, the current study is the first large‐scale study to demonstrate the impact of EBV antibodies on the prognosis of patients with non‐metastatic NPC from a population with a high prevalence of both EBV infection and NPC. Our study findings did not confirm the role of EA‐IgA and VCA‐IgA as prognostic biomarkers in patients with NPC and undetectable pEBV DNA. However, it is plausible that EA‐IgA and VCA‐IgA may enhance patient stratification by providing an additional layer of information on disease burden. In support of this suggestion, EA‐IgA and VCA‐IgA were positively associated with T stage, N stage and overall stage.
Li–CO2 batteries are regarded as a promising candidate for the next‐generation high‐performance electrochemical energy storage system owing to their ultrahigh theoretical energy density and ...environmentally friendly CO2 fixation ability. Until now, the majority of reported catalysts for Li–CO2 batteries are in the powder state. Thus, the air electrodes are produced in 2D rigid bulk structure and their electrochemical properties are negatively influenced by binder. The nondeformable feature and unsatisfactory performance of the cathode have already become the main obstacles that hinder Li–CO2 batteries toward ubiquity for wearable electronics. In this work, for the first time, a flexible hybrid fiber is reported comprising highly surface‐wrinkled and N‐doped carbon nanotube (CNT) networks anchored on metal wire as the cathode integrated with high performance and high flexibility for fiber‐shaped Li–CO2 battery. It exhibits a large discharge capacity as high as 9292.3 mAh g−1, an improved cycling performance of 45 cycles, and a decent rate capability. A quasi‐solid‐state flexible fiber‐shaped Li–CO2 battery is constructed to illustrate the advantages on mechanical flexibility of this fiber‐shaped cathode. Experiments and theoretical simulations prove that those doped pyridinic nitrogen atoms play a critical role in facilitating the kinetics of CO2 reduction and evolution reaction, thereby enabling distinctly enhanced electrochemical performance.
A flexible hybrid fiber comprising highly surface‐wrinkled and N‐doped carbon nanotube (CNT) networks anchored on metal wire as the cathode integrated with high performance and high flexibility is reported for fiber‐shaped flexible Li–CO2 batteries. Abundant catalytic active sites originating from highly‐wrinkled surfaces and enhanced reaction kinetics by doped pyridinic nitrogen atoms improve the electrochemical performance of the battery.
Increasing evidence has revealed the roles of long noncoding RNAs (lncRNAs) as tumor biomarkers. Here, we introduce an immune-associated nine-lncRNA signature for predicting distant metastasis in ...locoregionally advanced nasopharyngeal carcinoma (LA-NPC). The nine lncRNAs are identified through microarray profiling, followed by RT-qPCR validation and selection using a machine learning method in the training cohort (n = 177). This nine-lncRNA signature classifies patients into high and low risk groups, which have significantly different distant metastasis-free survival. Validations in the Guangzhou internal (n = 177) and Guilin external (n = 150) cohorts yield similar results, confirming that the signature is an independent risk factor for distant metastasis and outperforms anatomy-based metrics in identifying patients with high metastatic risk. Integrative analyses show that this nine-lncRNA signature correlates with immune activity and lymphocyte infiltration, which is validated by digital pathology. Our results suggest that the immune-associated nine-lncRNA signature can serve as a promising biomarker for metastasis prediction in LA-NPC.
The aim of this trial was to address whether elective ipsilateral upper-neck irradiation (UNI) sparing the uninvolved lower neck provides similar regional relapse-free survival compared with standard ...whole-neck irradiation (WNI) in patients with nasopharyngeal carcinoma.
This open-label, non-inferiority, randomised, controlled, phase 3 trial was done at three Chinese medical centres. Patients aged 18–65 years with untreated, non-keratinising, non-distant metastatic (M0) nasopharyngeal carcinoma; with N0–N1 disease (according to International Union Against Cancer–American Joint Committee on Cancer TNM classification, seventh edition); and a Karnofsky performance status score of 70 or higher were randomly assigned (1:1) to receive elective UNI or WNI of the uninvolved neck. Total radiation doses of 70 Gy (for the primary tumour volume and the enlarged retropharyngeal nodes), 66–70 Gy (for the involved cervical lymph nodes), 60–62 Gy (for the high-risk target volume), and 54–56 Gy (for the low-risk target volume) were administered in 30–33 fractions, five fractions per week. Patients with stage II–IVA disease were recommended to receive combined intravenous cisplatin-based chemotherapy (either induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone). Randomisation was done centrally by the Clinical Trials Centre of Sun Yat-sen University Cancer Centre by means of a computer-generated random number code with a block size of four. Patients were stratified according to treatment centre and nodal status. Investigators and patients were not masked to treatment allocation. The primary endpoint was regional relapse-free survival in the intention-to-treat population. Non-inferiority was indicated if the upper limit of the 95% CI of the difference in 3-year regional relapse-free survival between the UNI and WNI groups was within 8%. Adverse events were analysed in the safety population (defined as all patients who commenced the randomly assigned treatment). This study is registered with ClinicalTrials.gov, NCT02642107, and is closed.
Between Jan 22, 2016, and May 23, 2018, 446 patients from 469 screened were randomly assigned to receive UNI (n=224) or WNI (n=222). Median follow-up was 53 months (IQR 46–59). 3-year regional relapse-free survival was similar in the UNI and WNI groups (97·7% 95% CI 95·7–99·7 in the UNI group vs 96·3% 93·8–98·8 in the WNI group; difference −1·4% 95% CI −4·6 to 1·8; pnon-inferiority<0·0001). Although acute radiation-related toxic effects were similar between the groups, the incidence of late toxicity was lower in the UNI group than in the WNI group, including any-grade hypothyroidism (66 30% of 222 patients vs 87 39% of 221), skin toxicity (32 14% vs 55 25%), dysphagia (38 17% vs 71 32%), and neck tissue damage (50 23% vs 88 40%). No patients died during treatment. After treatment, one patient in the WNI group died from a non-cancer-related cause (dermatomyositis).
Elective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0–N1 nasopharyngeal carcinoma.
Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province, and the Overseas Expertise Introduction Project for Discipline Innovation.
For the Chinese translation of the abstract see Supplementary Materials section.
Transcription factors (TFs) engage in various cellular essential processes including differentiation, growth and migration. However, the master TF involved in distant metastasis of nasopharyngeal ...carcinoma (NPC) remains largely unclear. Here we show that KLF5 regulates actin remodeling to enhance NPC metastasis. We analyzed the msVIPER algorithm-generated transcriptional regulatory networks and identified KLF5 as a master TF of metastatic NPC linked to poor clinical outcomes. KLF5 regulates actin remodeling and lamellipodia formation to promote the metastasis of NPC cells in vitro and in vivo. Mechanistically, KLF5 preferentially occupies distal enhancer regions of ACTN4 to activate its transcription, whereby decoding the informative DNA sequences. ACTN4, extensively localized within actin cytoskeleton, facilitates dense and branched actin networks and lamellipodia formation at the cell leading edge, empowering cells to migrate faster. Collectively, our findings reveal that KLF5 controls robust transcription program of ACTN4 to modulate actin remodeling and augment cell motility which enhances NPC metastasis, and provide new potential biomarkers and therapeutic interventions for NPC.
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•Co(OH)(NO3) (CoNH) is adopted to instantaneously realize oriented atom substitution and vacancies generation.•The atom substitutional doping for S/Se/Mo/P into CoNH can be ...accomplished.•The electron arrangement, chemical environment, and adsorption ability are obtained.•This work provides fresh light on the accurate atom incorporation and vacancy engineering.
The accurate identification and manipulation for synergistic atom substitution and vacancy is significant and challenging for the overall water splitting (OWS) and theoretical analysis. Herein, a unique Co(OH)(NO3) (CoNH) material has been adopted to instantaneously realize oriented atom substitution and vacancies generation through fast impregnation. We found that in alkaline solution, the nitrate groups are prone to dissolve, thus forming nitrate vacancies that are the preferential sites for foreign atoms. Therefore, the controlled atom substitutional doping and vacancies can be simultaneously accomplished. As verification, after dipping in respective solution, S/Se/Mo/P was doped and nitrate deficiencies formed. The atom replacement and vacancy synergistically modulate the electron arrangement, chemical environment, and adsorption capability of host materials, thus boosting electrocatalytic OWS activity. In addition, the precise structure with definite lattice is propitious for the reveal of the structure–property connection. By theory calculation, the optimized electronic structure and adsorption ability of well-defined structures are also uncovered. This present work is expected to shed fresh light on accurate atom incorporation and vacancy engineering, thus achieving a deeper understanding of the structure-composition-property relationship.
Frontier evidence suggests that dysregulation of long noncoding RNAs (lncRNA) is ubiquitous in all human tumors, indicating that lncRNAs might have essential roles in tumorigenesis. Therefore, an ...in-depth study of the roles of lncRNA in nasopharyngeal carcinoma (NPC) carcinogenesis might be helpful to provide novel therapeutic targets. Here we report that lncRNA TINCR was significantly upregulated in NPC and was associated positively with poor survival. Silencing TINCR inhibited NPC progression and cisplatin resistance. Mechanistically, TINCR bound ACLY and protected it from ubiquitin degradation to maintain total cellular acetyl-CoA levels. Accumulation of cellular acetyl-CoA promoted
lipid biosynthesis and histone H3K27 acetylation, which ultimately regulated the peptidyl arginine deiminase 1 (PADI1)-MAPK-MMP2/9 pathway. In addition, insulin-like growth factor 2 mRNA-binding protein 3 interacted with TINCR and slowed its decay, which partially accounted for TINCR upregulation in NPC. These findings demonstrate that TINCR acts as a crucial driver of NPC progression and chemoresistance and highlights the newly identified TINCR-ACLY-PADI1-MAPK-MMP2/9 axis as a potential therapeutic target in NPC. SIGNIFICANCE: TINCR-mediated regulation of a PADI1-MAPK-MMP2/9 signaling pathway plays a critical role in NPC progression and chemoresistance, marking TINCR as a viable therapeutic target in this disease.
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