Treatment Of Nasopharyngeal Carcinoma Research Articles

Efficacy and safety of Anlotinib in combination with gemcitabine and cisplatin as a first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A single-arm clinical trial.

The effectiveness and safety of combining anlotinib with gemcitabine and cisplatin in the first-line treatment of recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) have not been definitively established. This research seeks to investigate the potential benefits and risks of utilizing this combination therapy in the first-line management of R/M NPC. The research involved 22 individuals diagnosed with R/M NPC and who had not undergone any previous treatment. These patients were administered a concomitant therapy of anlotinib, gemcitabine, and cisplatin in cycles occurring every 3 weeks. The primary focus of the study was to assess progression-free survival (PFS), while secondary endpoints included overall survival (OS), disease control rate (DCR), and objective response rate (ORR). The findings revealed that the median PFS duration for patients with R/M NPC receiving the GPA regimen as a first-line treatment was 12.6 months, with a 95% confidence interval (CI): 0.1 to 25.2. The median OS was reported as 37.4 months, with 95% CI: 28.0 to 46.8. The DCR in this study was 95.5%, while the ORR was 63.6%. Anlotinib has demonstrated a degree of effectiveness in the initial treatment of R/M NPC, while maintaining an acceptable level of safety.

Targeting EGFR-binding protein SLC7A11 enhancing antitumor immunity of T cells via inducing MHC-I antigen presentation in nasopharyngeal carcinoma

Approximately 80% of nasopharyngeal carcinoma (NPC) patients exhibit EGFR overexpression. The overexpression of EGFR has been linked to its potential role in modulating major histocompatibility complex class I (MHC-I) molecules. We discovered that EGFR, operating in a kinase-independent manner, played a role in stabilizing the expression of SLC7A11, which subsequently inhibited MHC-I antigen presentation. This mechanism, in turn, provided protection to NPC cells against T cell-mediated cytotoxicity. The underlying molecular processes revealed that the high and stable expression of SLC7A11 hindered the nuclear entry of GR, thereby suppressing TAP1 transcription and the presentation of MHC-I molecules. Additionally, elevated SLC7A11 expression led to an increase in FAF2 expression and triggered ERAD-dependent degradation of MHC-I, resulting in a reduction of MHC-I molecules on the cell membrane. The NPC patients exhibiting high EGFR and low MHC-I expression, combined with a scarcity of CD8+ T cells (EGFRhighMHC-IlowCD8few phenotype), experienced considerably shorter overall survival times compared to other situations. What is more, our study demonstrated that sorafenib had the capability to enhance the MHC-I antigen presentation process, thereby facilitating T cell-mediated killing of NPC cells via targeting SLC7A11. Consequently, targeting SLC7A11 with sorafenib emerges as a promising therapeutic strategy for the treatment of NPC.

RNF138 contributes to cisplatin resistance in nasopharyngeal carcinoma cells

Resistance to chemotherapy is a significant concern in the treatment of nasopharyngeal carcinoma (NPC), and occurs due to various mechanisms. This study is aimed to evaluate the effects of RING finger protein 138 (RNF138) in the development of cisplatin resistance to NPC. After gene overexpression and silencing, the expression levels of RNF138 were evaluated. The impacts of RNF138 on the proliferation and apoptosis rate of NPC cells were then assessed. γ-H2AX-mediated DNA damage was determined via immunofluorescence assay. Moreover, a tumor xenograft mouse model was developed to investigate the role of RNF138 on NPC progression in vivo. Additionally, transcriptome analysis was performed in 5–8 F cells transfection with OE-RNF1138 or OE-NC.Cisplatin significantly inhibited the proliferation, and promoted apoptosis and DNA damage in NPC cells; however, overexpression of RNF138 reversed the aforementioned regulatory role of cisplatin on NPC cells. Knockdown of RNF138 resulted in contrasting phenotypic outcomes. Additionally, in nude mice, RNF138 overexpression attenuated the suppressive effects of cisplatin on the growth of xenograft tumor, while RNF138 silencing further enhanced the inhibiting role of cisplatin. We further indicated that in 5–8 F cells following RNF138 overexpression, some pathways such as PI3K-Akt signaling pathway, human papillomavirus infection and ErbB signaling pathway that have been reported to be associated with NPC progression and cisplatin resistance were significantly enriched. These findings indicate that the modulation of RNF138 could potentially address the issue of chemotherapy failure by overcoming cisplatin resistance in NPC cells, making it a promising candidate for targeted drug therapy.

MUC5B regulates alterations in the immune microenvironment in nasopharyngeal carcinoma via the Wnt/β-catenin signaling pathway

ObjectiveTo screen potential differentially expressed genes related to immune function in nasopharyngeal carcinoma through an online database, and to verify their mechanism of action, so as to provide a reference for the diagnosis and treatment of nasopharyngeal carcinoma in the future.MethodsDifferentially expressed genes were analyzed from the GSE227541 dataset, and functional enrichment analysis was conducted. With mucin 5B, oligomeric mucus/gel-forming as the focus, the correlation between its expression and immune indexes was analyzed by using the TIMER database. The expressions of mucin 5B, oligomeric mucus/gel-forming in clinical NPC tissues and adjacent tissue samples were detected Furthermore, mucin 5B, oligomeric mucus/gel-forming abnormal expression vectors were constructed and transfected into human NPC cell CNE-2Z to detect alterations in cell activity, ferroptosis and the immune microenvironment. In addition, the role of the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma was observed, and the influence of mucin 5B, oligomeric mucus/gel-forming on this pathway was discussed.ResultsA total of 42 differentially expressed genes were found in the GSE227541 dataset, among which mucin 5B, oligomeric mucus/gel-forming was obviously at the core of the entire network. In nasopharyngeal carcinoma tissues, the research team observed the upregulated expression of mucin 5B, oligomeric mucus/gel-forming (P < 0.05). In vitro, increased expression of elevated mucin 5B, oligomeric mucus/gel-forming activates nasopharyngeal carcinoma cell activity and immune escape and inhibits ferroptosis. In terms of pathways, upregulating mucin 5B, oligomeric mucus/gel-forming expression could activate the Wnt/β-catenin pathway.ConclusionsMucin 5B, oligomeric mucus/gel-forming regulates the immune escape of nasopharyngeal carcinoma cells and participates in tumor progression by mediating the Wnt/β-catenin signaling pathway.

The multi-target mechanism of action of Selaginella doederleinii Hieron in the treatment of nasopharyngeal carcinoma: a network pharmacology and multi-omics analysis

Nasopharyngeal carcinoma (NPC) presents significant treatment challenges due to its complex etiology and late-stage diagnosis. The traditional Chinese medicine Selaginella doederleinii Hieron (S. doederleinii) has shown potentiality in NPC treatment due to its multi-target, multi-pathway anti-cancer mechanisms. First, we identified NPC related target genes from databases like GeneCards, OMIM, and DisGeNET, and performed WGCNA analysis on the GSE53819 dataset to identify several important gene modules related to NPC. Active components and their targets in S. doederleinii were screened from the TCMSP and other databases, identifying 32 overlapping genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these genes are primarily involved in critical biological processes like protein phosphorylation and cell cycle regulation. A protein–protein interaction network was constructed, and cytoHubba identified six key genes (BCL2, MAPK14, ABCB1, PLK1, ATM, HMOX1). Kaplan–Meier analysis and immune infiltration analysis further showed that these key genes are closely related to the prognosis and immune microenvironment of NPC patients. Single-cell RNA sequencing analysis revealed the expression distribution of key genes across different immune cell types and explored their roles in the differentiation process of malignant cells through pseudotime trajectory analysis. Molecular docking and dynamics simulation results indicated that the Berberine-MAPK14 and Matairesinol-PLK1 complexes have high binding affinity and stability. Binding free energy calculations confirmed the stability of these complexes. Based on our comprehensive multi-level analysis, the active components of S. doederleinii may play a significant role in the treatment of NPC through multi-pathway and multi-target synergistic effects.

Changing Landscape of Head and Neck Squamous Cell Carcinoma and Nasopharyngeal Carcinoma Treatment and Survival Trends in Thailand: A 13-Year Multicenter Retrospective Study of Patients.

The incidence and survival rates of head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC) vary globally, influenced by factors such as ethnicity, lifestyle, and health care systems. A retrospective analysis was conducted on patients with HNSCC treated between 2008 and 2020 in four major Thai academic cancer centers, using a multidisciplinary multicenter database. The study focused on the evolution of patient characteristics, survival changes, and treatment landscape alterations over time. Among 6,319 patients, the most common primary sites were nasopharynx (33%), oral cavity (23%), oropharynx (17%), larynx (15%), and hypopharynx (8%). An increase in human papillomavirus-related oropharyngeal carcinoma was noted, from 13% in 2008 to 42% in 2019-2020. The majority of patients presented with locally advanced (LA) stages (IVa/b: 50%, III: 26%). Chemoradiotherapy (54%) and surgery (24%) were the main treatments, with cisplatin (79%) being most commonly used in chemoradiation. Overall survival (OS) improved annually across all subsites, correlating with an increase in intensity-modulated radiotherapy (IMRT) use, from 25% in 2008 to 90% in 2019-2020. The median follow-up duration was 4.59 years, with a minimum of 2.75 years. Patients treated with IMRT had significantly longer OS compared with those treated with non-IMRT techniques, in both NPC and non-NPC HNSCC (P < .001). To our knowledge, this is the largest study in Thailand that demonstrates increasing survival outcomes in patients with HNSCC and NPC, despite commonly presenting with LA stages. The increasing use of IMRT may be contributing to improved survival outcomes in both patients with NPC and non-NPC HNSCC patients.

Programmed cell death in nasopharyngeal carcinoma: Mechanisms and therapeutic targets.

Programmed cell death is a type of autonomic and orderly cell death mode controlled by genes that maintain homeostasis and growth. Tumor is a typical manifestation of an imbalance in environmental homeostasis in the human body. Currently, several tumor treatments are designed to trigger the death of tumor cells. Nasopharyngeal carcinoma is one of the most common malignant tumors in China. It displays obvious regional and ethnic differences in its incidence, being typically high in the south and low in the north of China. Nasopharyngeal carcinoma is currently considered to be a polygenic inherited disease and is often mediated by the interaction between multiple genes or between genes and the environment. Apoptosis has long been considered the key to tumor treatment, while other cell death pathways have often been overlooked. The current study provides an overview of the relationship among apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and nasopharyngeal carcinoma, and the regulatory pathways of nasopharyngeal carcinoma based on five cell death modes were synthesized from the view of molecule. We hope this review will help explore additional, novel programmed cell death targets for the treatment of nasopharyngeal carcinoma and thus promote in-depth research.

Exosomes derived from cancer-associated fibrolasts mediated ciplatin resistance

Objective: Nasopharyngeal carcinoma (NPC), a highly invasive form of head and neck cancer, carries a significant risk of distant metastasis. NPC is particularly prevalent in Asia and has a high incidence in southern China. Cisplatin-diamminedichloroplatinum (DDP), a chemotherapy agent, is commonly employed in NPC treatment. Despite DDP’s efficacy, many patients eventually develop resistance to it over the course of their therapy, which significantly hinders treatment outcomes. Cancer-associated fibroblasts (CAFs) are key components of the tumor micro-environment and contribute to tumor progression and chemotherapy resistance. Exosomes secreted by CAFs serve as crucial mediators of intercellular communication and participate in modulating diverse biological processes. This study aimed to explore how exosomes derived from CAFs contribute to DDP resistance in NPC. Material and Methods: An in vitro coculture system was used to simulate the interaction between CAFs and NPC cells, and exosomes secreted by CAFs were isolated and characterized. The expression of autophagy hallmark proteins was detected by Western blot and quantitative real-time polymerase chain reaction. Autophagy intensity was quantified using monodansylcadaverine staining, and cell proliferation was assessed by colony formation assays and methylthiazolyldiphenyl–tetrazolium assays. NPC cells were treated with autophagy inducers (rapamycin), and the expression of Ras homologue enriched in brain (Rheb), mammalian target of rapamycin complex (mTORC1), and UNC51-like kinase was detected. Immunofluorescence was used to determine the cellular localization and expression intensity of mTORC1, and the effect on DDP sensitivity was evaluated through cell proliferation rates. In addition, the exosome-mediated resistance mechanism was further validated using an in vivo xenograft tumor model. Results: Coculture of CAFs with NPC cells significantly promoted the proliferation of NPC cells (P &lt; 0.01), significantly elevated the IC50 value of DDP (P &lt; 0.01), and elevated the resistance of NPC cells to DDP. CAF-derived exosomes elevated autophagy hallmark proteins light chain 3B-II, Beclin, and increased the autophagy intensity (P &lt; 0.01). CAF-derived exosomes promoted autophagy by inhibiting mTORC1 (P &lt; 0.01). In the in vitro model, exosomes promoted the growth of tumor tissues (P &lt; 0.01), and the inhibition of exosome secretion reversed the promotion effect of autophagy (P &lt; 0.01) and elevated the sensitivity of NPC cells to DDP. Conclusion: CAF-derived exosomes promote protective autophagy in NPC cells through the Rheb/mTOR axis, and result in DDP resistance in NPC.

The Role of PD-1/PD-L1 Inhibitors in the Treatment of Nasopharyngeal Carcinoma in the Epstein-barr Virus Microenvironment

This article offers an extensive examination of nasopharyngeal carcinoma (NPC), with a particular emphasis on its epidemiological features, relationship with Epstein-Barr virus (EBV) infection, classification system, and current immunotherapy approaches. NPC is notably prevalent in East and Southeast Asia, displaying a robust association with EBV infection, particularly in the non-keratinized subtype. Considering the successful implementation of PD-1/PD-L1 immune checkpoint substance across various cancer, their potential therapeutic benefits in NPC have attracted considerable attention. Although PD-1/PD-L1 inhibitors have exhibited effectualness in NPC patients, the response rate remains inconsistent, suggesting a requirement for deeper investigation into the regulatory mechanisms that govern PD-L1 expression. Furthermore, the approach of combined interferon therapy, designed to augment anti-tumor immunity, has demonstrated potential in enhancing therapeutic outcomes and extending patient survival when administered concomitantly with PD-1/PD-L1 inhibitors. However, several obstacles remain, including drug resistance and the substantial heterogeneity observed in NPC tumors. Tumors from different patients display variations in gene expression patterns, immune microenvironment composition, and other factors, which may lead to divergent patient responses to the combined treatment regimen of PD-1/PD-L1 inhibitors and interferon. This article highlights the research significance of PD-1/PD-L1 combined with interferon in NPC treatment and anticipates its extensive clinical application in the future. Nonetheless, to achieve this goal, several challenges must be tackled through persistent and rigorous research and exploration.

EBV-induced upregulation of CD55 reduces the efficacy of cetuximab treatment in nasopharyngeal carcinoma

Cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody, has been shown to improve survival in nasopharyngeal carcinoma (NPC) patients. However, a correlation between the expression of EGFR and the response to cetuximab has not been observed, indicating that the mechanism underlying the effects of cetuximab needs to be further elucidated. The antitumour response involves immunotherapeutic mechanisms that target tumour-associated antigens, including complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC), act either alone or, more often, in combination. However, EBV infected NPC cells often develop resistance mechanisms that allow them to evade immune surveillance. Here, we found that overexpression of the complement-regulated protein CD55 in EBV-associated NPC cells mainly suppresses ADCC activity thus reduces the efficacy of cetuximab. Mechanistically, EBV latent membrane protein 1 (LMP1) mediated upregulation of CD55 through the NF-κB signalling pathway. The present study provides a rationale for the development of CD55 inhibitors to improve the clinical efficacy of cetuximab in NPC.

LncRNA C7orf13 facilitates cell proliferation and metastasis in nasopharyngeal carcinoma via targeting miR‐449c/miR‐28‐5p‐FMNL2 axis

AbstractThis study was to determine the involvement of long non‐coding RNA C7orf13 in nasopharyngeal carcinoma (NPC) and its underlying mechanism. Real‐time quantitative PCR results indicated that C7orf13 was overexpressed in NPC and associated with malignant features. C7orf13 knockdown significantly suppressed the proliferation, migration and invasion of NPC cells. Furthermore, we found that C7orf13 sequestered miR‐449c and miR‐28‐5p in NPC cells by dual‐luciferase reporter assays and RNA immunoprecipitation analysis. Sequent experiments showed that C7orf13 has a positive relationship with formin‐like 2 (FMNL2) in NPC tissues. Moreover, C7orf13 knockdown weakened FMNL2‐mediated cell invasion and migration. Finally, functional experiments revealed that the positive effect of C7orf13 on cell migration and invasion was mediated by the miR‐449c/miR‐28‐5p‐FMNL2 axis. Generally, our study identifies the biological role of long non‐coding RNA C7orf13 in the malignant process of NPC, which may pave a new way for the diagnosis and treatment of NPC.

Fluorinated polyethyleneimine vectors with serum resistance and adjuvant effect to deliver LMP2 mRNA vaccine for nasopharyngeal carcinoma therapy.

Latent membrane protein 2 (LMP2), which is an important protein of Epstein-Barr virus (EBV) in the latent phase to mediate metastasis and recurrence, has shown great potential as a targeting antigen in mRNA vaccine for nasopharyngeal carcinoma (NPC) therapy. In this study, an LMP2 mRNA vaccine was developed based on a serum-resistant fluorinated polyethyleneimine (TKPF) with the self-adjuvant effect for achieving a strong anti-tumor immunity in NPC treatment. Specifically, the proposed vaccine PEG[TKPF/mLMP2] was comprised of a TKPF/mLMP2 core formed by the cationic TKPF and LMP2 mRNA, together with a dialdehyde poly (ethyl glycol) (OHC-PEG-CHO) coating. PEG[TKPF/mLMP2] showed less protein absorption to enable serum resistance to maintain ∼50 % transfection efficiency under 50 % FBS media. In addition, PEG[TKPF/mLMP2] could render enhanced internalization and lysosomal escape of mRNA by DC cells via positive charge and fluorine groups, followed by efficient transfection and expression, eventually triggering DC maturation and antigen presentation to T cells as demonstrated by in vitro studies. The activated antigen-specific T cells would attack tumor cells expressing LMP2 and release pro-inflammatory cytokines including IFN-γ, IL-6, and TNF-α. Furthermore, in vivo studies manifested effective spleen transfection and activated T cells by PEG[TKPF/mLMP2] to prevent tumor cell growth and prolong mouse survival in both prophylactical and therapeutical models. Notably, PEG[TKPF] revealed self-adjuvant effect to induce a strong immune response for boosting the anti-tumor potency of LMP2 mRNA. In summary, the fabricated LMP2 mRNA vaccine facilitated by the efficient and self-adjuvant vector induced robust immunotherapeutic efficacy, providing a possible solution for NPC therapy. STATEMENT OF SIGNIFICANCE: Latent membrane protein 2 (LMP2), which is a key Epstein-Barr virus (EBV) protein for metastasis and recurrence, can be targeted as an antigen for mRNA vaccine development to treat nasopharyngeal carcinoma (NPC). However, the current LMP2 vaccine is still inefficient in inducing potent anti-NPC immunity. Although mRNA has emerged as an effective tool to rejuvenate LMP2 vaccine development, it still suffers from vulnerability to serum conditions and weak immune response. In this study, we developed an LMP2 mRNA vaccine based on a serum-resistant fluorinated polyethyleneimine (TKPF) with self-adjuvant effects to achieve strong anti-tumor immunity in NPC treatment. The proposed PEG[TKPF/mLMP2] vaccine efficiently delivers to dendritic cells (DCs) for activating T cell maturation, ultimately suppressing the growth of LMP2-expressing tumors in both prophylactic and therapeutic mouse models.

CircKRT75 augments the cisplatin chemoresistance of nasopharyngeal carcinoma via targeting miR-659/CCAR2 axis.

Cisplatin resistance is a clinical challenge limiting the treatment of nasopharyngeal carcinoma (NPC). CircRNAs have been evidenced as key molecules involved in tumor advancement and drug resistance. The present study aimed to elucidate the potential biological value of circKRT75 in NPC cisplatin resistance. CircKRT75 levels in NPC clinical samples and parental/resistant cell lines were analyzed based on qRT-PCR. CCK-8 and flow cytometry were adopted to assess the impacts of circKRT75 on the growth viability and apoptotic ability of NPC resistant cells. Meanwhile, western blot was performed to detect changes in the expression of apoptosis-related proteins. Bioinformatics analysis predicted miRNAs and mRNAs downstream of circKRT75, and the interaction between circKRT75 and downstream targets was validated by RNA pull-down, dual-luciferase reporter and rescue experiments. CircKRT75 was notably enhanced in NPC tissues and NPC cisplatin-resistant cells. Functional experiments disclosed that circKRT75 silencing repressed NPC-resistant cell growth and promoted apoptosis. Bioinformatics screening identified that circKRT75 performed as a molecular sponge for miR-659, and CCAR2 was a direct target of miR-659. Further rescue assays confirmed that miR-659 inhibitor restored the inhibitory effect of circKRT75 knockdown on the growth of drug-resistant cells, while CCAR2 silencing could reverse the promotion of NPC cisplatin resistance by circKRT75 upregulation. Additionally, animal experiments revealed that circKRT75 knockdown restrained NPC cisplatin resistance in vivo. CircKRT75 contributed to cisplatin resistance in NPC through miR-659/CCAR2 signaling, which provided a novel perspective and direction to solve the problem of chemoresistance in NPC.

LncRNA SNHG14 Facilitates Cisplatin Resistance Through Upregulating Notch2 via Binding to U2AF2 in Nasopharyngeal Carcinoma.

Cisplatin (DDP) is one of the commonly used chemotherapeutic drugs for nasopharyngeal carcinoma (NPC) patients, and the resistance of tumor cells to cisplatin is main obstacle for NPC treatment. This study explored effect and possible mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) on drug resistance of NPC cells to cisplatin. Levels of SNHG14 and Notch2 in NPC tissues and cells were confirmed using RT-qPCR. Western blot detected Notch2 and ABCB1 expression in NPC cells. IC50 of cisplatin-treated NPC cells was tested utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell proliferation and apoptosis were evaluated utilizing colony formation experiment and flow cytometry, respectively. RNA immunoprecipitation (RIP) assay was utilized to validate the target genes of U2AF2. Notch2 mRNA stability was tested using actinomycin D. SNHG14 level was increased in both cisplatin-resistant NPC tissues and cell lines. SNHG14 silencing in HNE1/DDP cells resulted in inhibition of chemoresistance to cisplatin. Conversely, upregulation of SNHG14 in HNE1 cells enhanced their resistance to cisplatin. SNHG14 exhibited an interaction with U2AF2, leading to stabilization of Notch2 mRNA. Finally, Notch2 was involved in SNHG14-mediated cisplatin resistance in NPC cells. Our findings demonstrate SNHG14 plays a significant role in promoting chemoresistance of NPC cells to cisplatin through U2AF2/Notch2 axis. These results highlight potential therapeutic targets for NPC treatment.

CircINADL promotes nasopharyngeal carcinoma metastasis by inhibiting HuR ubiquitin degradation and disrupting the hippo signaling pathway

Distant metastasis is a primary factor contributing to the low survival rate of patients with nasopharyngeal carcinoma (NPC). Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer initiation and progression. However, the mechanisms underlying the abnormal expression and biological function of circRNA in NPC remain unclear. In this study, we identified a new circRNA, circINADL, which was upregulated in NPC tissues and positively correlated with the clinical stage of NPC. We found that the FUS RNA binding protein (FUS) promoted the transcription of circINADL in NPC cells. Elevated circINADL levels were shown to enhance NPC cells metastasis. Mechanistically, circINADL attenuated the interaction between human antigen R (HuR) and the E3 ubiquitin ligase β-TrCP, thereby inhibited the ubiquitination and degradation of HuR. Consequently, CircINADL enhanced the stability of the HuR target gene Yes1-associated transcriptional regulator (YAP1), leading to the dysregulation of the Hippo signaling pathway. In conclusion, our study reveals the function of circINADL in promoting NPC metastasis and highlights its potential as a biomarker and therapeutic target for NPC treatment.

HNRNPH1 stabilizes FLOT2 mRNA in a non-canonical m6A-dependent manner to promote malignant progression in nasopharyngeal carcinoma.

The mechanism underlying the upregulation of FLOT2 in tumors, especially its regulatory mechanism at the RNA level, remains unclear. The purpose of this study is to investigate the regulatory mechanism of FLOT2 upregulation in tumors, particularly at the RNA level, and its role in nasopharyngeal carcinoma (NPC) progression. We identified the role of HNRNPH1 in maintaining FLOT2 mRNA stability and its dependency on the m6A modification. We explored the interaction between HNRNPH1 and METTL14, a key enzyme in m6A modification, and its impact on FLOT2 mRNA stability. We also assessed the expression levels of HNRNPH1 and METTL14 in NPC and their correlation with patient malignancy and prognosis. Experimental approaches included in vitro and in vivo assays to study the effects of HNRNPH1 knockdown on NPC cell proliferation and invasion. HNRNPH1 is highly expressed in NPC and stabilizes FLOT2 mRNA through an m6A-dependent mechanism. HNRNPH1 interacts with METTL14 to prevent its degradation by STUB1 E3 ligases, leading to increased m6A modification of FLOT2 by METTL14. Additionally, IGF2BP3 was shown to recognize the m6A modification on FLOT2 mRNA, further stabilizing it. High expression of HNRNPH1 and METTL14 were observed in NPC and were positively associated with increased malignancy and poorer patient outcomes. HNRNPH1 knockdown significantly reduced the proliferation and invasive capabilities of NPC cells. Restoration of METTL14 in HNRNPH1-depleted cells could rescue FLOT2 expression and the malignant phenotype, but this effect was negated by the knockdown of FLOT2. Our study elucidates a novel mechanism where HNRNPH1 and METTL14 work together to maintain the stability of FLOT2 mRNA, thereby promoting NPC progression. Targeting this pathway presents a promising therapeutic strategy for the treatment of NPC.

Exploration of the value of concurrent chemotherapy for T2N1 nasopharyngeal carcinoma under intensity modulated radiotherapy mode.

In the era of intensity-modulated radiation therapy (IMRT), the status of concurrent chemoradiotherapy(CCRT) for stage II nasopharyngeal carcinoma(NPC), particularly for patients in T2N1 subtype, remains controversial nowadays. This study exclusively aims to explore the value of concurrent chemotherapy in the treatment of T2N1 NPC under IMRT mode. A retrospective analysis was conducted on 218 cases of T2N1 NPC patients treated at our hospital from January 2015 to December 2020, comprising 75 cases treated with IMRT and 143 cases treated with CCRT. The study compared therapeutic outcomes and side effects between the two groups. The 5-year progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRRFS) and,distant metastasis-free survival (DMFS) estimated by the K-M method for the IMRT vs. CCRT groups were 86.1% vs. 85.1%,89.3% vs. 87.9%, 95.9% vs. 94.9%,and 90.2% vs. 89.1%, respectively, with no statistically significant differences (Log-rank P>0.05 for all comparisons). Cox regression analysis identified Epstein-Barr virus (EBV) DNA copy level (≥1000 vs. <1000 copies/ml)(the cutoff value was determined through the ROC curve), lymph node necrosis (yes vs. no) and extra-nodal extension (yes vs. no) as independent prognostic factors for PFS(P<0.05 for all comparisons). Subgroup analysis indicated an interaction effect between lymph node necrosis (yes vs. no) and treatment modality (IMRT vs. CCRT) regarding PFS (P for interaction<0.05). In the subgroup with lymph node necrosis, IMRT compared to CCRT had a poorer prognosis (HR: 1.85,95% CI: 1.02-3.50). CCRT was noted to increase acute hematological, gastrointestinal and other toxicities. This study provides a reference for clinical treatment decisions in T2N1 NPC. For the entire population of T2N1 NPC, the therapeutic effects of IMRT and CCRT are comparable, with increased acute toxicities in the latter. However, for patients with EBV-DNA copy level ≥1000 copies/ml, lymph node necrosis and extra-nodal extension, CCRT may be considered as appropriate. Particularly, patients with lymph node necrosis may be potential beneficiaries for CCRT.

Risk Factors for Unplanned Emergency Department Visits in Patients with Nasopharyngeal Carcinoma During Radiotherapy.

Background/Objectives: Nasopharyngeal carcinoma (NPC) is commonly treated with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). However, unplanned emergency department (ED) visits during treatment can disrupt therapy and impact patient outcomes. This study aims to identify the risk factors associated with unplanned ED visits in patients with NPC receiving RT or CCRT. Methods: We retrospectively analyzed 2111 patients with NPC treated between 2001 and 2019 at Chang Gung Memorial Hospital. Patients were categorized based on whether they experienced an unplanned ED visit during or up to three months post-treatment. Demographic and clinical variables were compared using the Chi-squared test, and survival outcomes were assessed using Kaplan-Meier analysis. Results: Among the cohort, 573 patients (27.2%) experienced at least 1 unplanned ED visit. Risk factors for unplanned ED visits included older age (p < 0.001), hypertension (p < 0.001), higher Charlson Comorbidity Index (p = 0.001), and advanced clinical stage (T stage, p = 0.0046; N stage, p = 0.0034; M stage, p = 0.0008). No significant difference in ED visit rates was observed between RT alone and CCRT groups. Conclusions: Unplanned ED visits were common during NPC treatment, with risk factors primarily related to patient age, comorbidities, and disease stage. Identifying high-risk patients may enable interventions to reduce ED visits, improve survival outcomes, and alleviate healthcare costs.

Surgical treatment of nasopharyngeal carcinoma

Surgical treatment of nasopharyngeal carcinoma

Concurrent chemoradiotherapy with S-1 versus platinum in the treatment of locoregionally advanced nasopharyngeal carcinoma: a multicenter, retrospective, propensity score-matched analysis.

Literature data are scarce on concurrent chemoradiotherapy (CCRT) with S-1 for locally advanced nasopharyngeal carcinoma (LANPC) treatment. This study compared the efficacy and safety of the S-1 versus platinum-based CCRT in LANPC treatment. Methods: This study enrolled 547 patients newly diagnosed with LANPC who underwent CCRT with S-1 or platinum at three institutions. Propensity score matching in a 1:1 ratio balancing baseline features was performed. Survival and adverse effects were compared between groups. Of 160 patients in the cohort, 100 eligible were propensity score matched. Matched dataset analyses showed a higher 5-year overall survival rate (87.1% vs. 84.7%, P = 0.833), progression-free survival (79.6% vs. 75.5%, P = 0.669), locoregional recurrence-free survival (87.0% vs. 84.7%, P = 0.518), and distant metastasis-free survival (84.8% vs. 83.0%, P = 0.780) in the S-1 group than in the platinum-based CCRT group, although not statistically significant. Objective response rate (98.0% vs. 88.0%, P = 0.117) was significantly higher in the S-1 than in the platinum-based regimen, although it was not statistically reflected. Compared with platinum-based, those undergoing S-1-based chemotherapy demonstrated a higher incidence of grade 3 mucositis (20.0% vs. 2.0%, P = 0.016) in the S-1 group and a lower incidence of leukopenia (44.0% vs. 68.0%, P = 0.033), neutropenia (28.0% vs. 52.0%, P = 0.032), anemia (22.0% vs. 44.0%, P = 0.040), nephrotoxicity (4.0% vs. 20.0%, P = 0.028), and nausea/vomiting (30.0% vs. 56.0%, P = 0.019). The results suggest that S-1 can be used as a concurrent chemotherapy regimen during radiotherapy for patients with LANPC, since it presents a noninferior survival benefit compared with platinum and shows tolerable adverse effects.