Nasopharyngeal carcinoma with leptomeningeal metastases has been treated with comprehensive treatment for long-term survival: A case report and literature review.

RATIONALE: Nasopharyngeal carcinoma has a high incidence in East and Southeast Asia, often with distant metastasis. However, leptomeningeal metastasis (LM) is extremely rare and usually has a poor prognosis. This paper reports the clinical treatment of a patient with meningeal metastasis of nasopharyngeal carcinoma (NPC) in order to improve the clinician's understanding of the disease. Early diagnosis of the disease can alleviate the pain of patients and prolong their survival time. PATIENT CONCERNS: We report the case of a 55-year-old female with a history of NPC with LM. Brain magnetic resonance imaging showed temporal lobe enhancement, peripheral edema, and enhancement of the adjacent meninges. Cerebrospinal fluid cytology suggests the presence of malignant tumor cells. DIAGNOSES: The patient was diagnosed with LM from NPC. INTERVENTIONS: The patients were regularly given targeted therapy with nimotuzumab, immunotherapy with karyolizumab, and lumbar intrathecal methotrexate chemotherapy and supportive treatment. OUTCOMES: The patient had survived for 3 years since the diagnosis of LM and was in good condition and still under active antitumor treatment. LESSONS: Leptomeningeal metastasis of NPC is a rare disease. Although there is currently no unified treatment plan, the neurological symptoms can still be controlled and the quality of life can be improved through active treatment.

Study on the value of Inhibin B in the diagnosis of nasopharyngeal carcinoma and its correlation with traditional Chinese medicine syndromes: An observational study.

To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum, and to evaluate the potential of Inhibin B as a new biomarker for NPC. Paraffin specimens of pathologically confirmed NPC tissues and paracancerous tissues were retrospectively collected, and the expression of Inhibin α (INHA) and Inhibin ßB (INHBB) was detected by SP method, and their relationship with clinicopathological indexes was analyzed; in addition, patients with NPC who had received radiotherapy were included as the study subjects, and Epstein-Barr virus DNA (EBV-DNA), INHA, and INHBB in patients were detected by using the fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and chemiluminescent immuno-sandwiching method, respectively. EBV-DNA, EBV-viral capsid antigen-immunoglobulin A (VCA IgA), INHA, and INHBB were detected in the patients, respectively, and their relationships with traditional Chinese medicine (TCM) patterns were also analyzed. The expression of INHA and INHBB in NPC tissues was lower than that in paracancerous tissues, and the expression of INHA in NPC patients was correlated with lymphatic metastasis, clinical staging, and TCM staging; the levels of EBV-DNA and VCA IgA were higher than that of healthy populations in NPC patients and were higher than that of patients with stage III + IV than that of patients with stage I + II, and the levels of INHA and INHBB were lower than those of healthy populations and were lower than those of patients with stage III + IV than that of patients with stage I + II. The levels of INHA and INHBB in nasopharyngeal cancer patients were lower than those in healthy people, and the levels in stage III + IV patients were lower than those in stage I + II patients. The levels of EBV-DNA and VCA IgA in nasopharyngeal cancer patients were correlated with the Chinese medicine patterns, and had different patterns. The expression of Inhibin B may be related to the progression of NPC, and it has certain typing significance for different TCM syndromes of NPC, which is helpful for TCM typing diagnosis.

New T staging recommendations for recurrent nasopharyngeal carcinoma.

OBJECTIVE: The International Union for Cancer Control/American Joint Committee on Cancer (UICC/AJCC) rT staging is not clinically practical for recurrent nasopharyngeal carcinoma (rNPC). The aim of this study was to establish a new rT staging to guide the treatment of rNPC. METHODS: We conducted a retrospective analysis of 175 patients diagnosed with rNPC between January 2012 and December 2020, using ROC curve analysis to evaluate its effectiveness. RESULTS: We analyzed the overall survival (OS) and progression-free survival(PFS) of patients diagnosed with rNPC according to the 8th (UICC/AJCC) rT staging, and found that the overall survival of rT1 and rT2 patients (OS; 29.98% vs. 27.09%, p = 0.8059) and progression-free survival (PFS; 28.48% vs. 26.12%, p = 0.4045) had no significant difference. In rT1 and rT2 patients of this study, overall survival(OS; 30.44% vs. 24.91%, p = 0.0229) and progression-free survival(PFS 29.12% vs. 24.03%, p = 0.0459) had a significant difference. Smoking, family history, and time interval of initial recurrence were independent prognostic factors for OS and PFS. CONCLUSION: The new rT staging of this study has a better predictive value for survival of rNPC patients than the 8th (UICC/AJCC) rT staging.

Locally advanced nasopharyngeal carcinoma in adolescents treated with tomotherapy: Experience at King Faisal Specialist Hospital and Research Centre.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare disease worldwide; To the best of our knowledge, there is no established standard of care specifically tailored for the adolescent population. The majority of existing research relies on retrospective data analysis. OBJECTIVE: Evaluate clinical features, treatment results, prognostic factors and late toxicities of locally advanced NPC patients treated with tomotherapy. DESIGN: Retrospective. SETTINGS: Tertiary care hospital. PATIENTS AND METHODS: Between January 2007 and January 2020, we treated patients with NPC, aged between 14 and 21 years, with concomitant chemoradiotherapy using tomotherapy at our institution. We prospectively collected details of clinical characteristics, treatment modalities, outcomes and prognostic factors of these patients and then analysed them retrospectively. MAIN OUTCOME MEASURES: 3-5 years overall survival (OS), 3-5 years locoregional control rate, 3-5 years disease-free survival (DFS), prognostic factors. SAMPLE SIZE: 51 patients. RESULTS: There were 26 male and 25 female patients included in our study. The mean age was 16.5 years, 5 (9.8%) patients with stage III, and 46 (90.2%) with stage IVa according to the American Joint Committee on Cancer, 8th edition staging system. Most patients (98%) received two or more cycles of induction chemotherapy. All patients received concomitant chemoradiotherapy. The median total dose of radiotherapy delivered was 6600 cGy (range 4800-7000). With a median follow-up of 73 months (range 9-168 months), a 5-year locoregional control rate, 5-year OS and 5-year DFS rates were 100%, 86.8% and 71.7%, respectively. Five years later, disease control was 71.7%. Ten (19.6%) patients had disease recurrence in the form of distant metastases during the follow up. CONCLUSIONS: Helical tomotherapy has an excellent late toxicity profile without compromising clinical outcome for patients with NPC. Radiotherapy remains the mainstay of treatment of nasopharyngeal carcinoma to achieve remarkable local control rates. LIMITATIONS: Single institution experience, small number of patients, and retrospective design.

Comparison of efficacy of neoadjuvant chemotherapy with gemcitabine plus cisplatin versus docetaxil, cisplatin, plus fluorouracil in locally advanced nasopharyngeal carcinoma.

Induction followed by concurrent chemoradiation (CCRT) is the standard of care for locally advanced nasopharyngeal carcinoma (LANPC). This study evaluated and compared the efficacy of two regimens of neoadjuvant chemotherapy along with CCRT in LANPC. Patients with LANPC were randomly divided in Group I (receiving neoadjuvant gemcitabine and cisplatin) and Group II (receiving neoadjuvant docetaxil, cisplatin and fluorouracil). Both groups also received concurrent single agent (i.e., cisplatin) chemotherapy and radiotherapy (70Gy). Treatment response was assessed at 8 weeks after the completion of CCRT using RECIST criteria. A total of 68 LANPC patients were enrolled. Group I comprised of 32 patients, with male to female ratio of 2.2, a mean (range, median) age of 38.6±11.3 (19-58, 36) years. Group II comprised of 36 patients, with male to female ratio of 3.5, mean (range, median) age of 40.9 ±11.6 (17-63, 40) years. The complete response was higher whereas the partial response was lower in Group I as compared to Group II (23/32 versus 16/36 and 06/32 versus 18/36, respectively). LANPC patients receiving gemcitabine plus cisplatin based neoadjuvant chemotherapy showed higher response, as compared with docetaxil, cisplatin and fluorouracil based neoadjuvant chemotherapy.

Downregulation of KLF5 by EBER1 via the ERK signaling pathway in EBV-positive nasopharyngeal carcinoma cells: implications for latent EBV infection.

Nasopharyngeal carcinoma (NPC) carcinogenesis and malignant transformation are intimately associated with Epstein-Barr virus (EBV) infection. A zinc-fingered transcription factor known as Krüppel-like factor 5 (KLF5) has been shown to be aberrantly expressed in a number of cancer types. However, little is known about the regulatory pathways and roles of KLF5 in EBV-positive NPC. Our study found that KLF5 expression was significantly lower in EBV-positive NPC than in EBV-negative NPC. Further investigation revealed that EBER1, which is encoded by EBV, down-regulates KLF5 via the extracellular signal-regulated kinase (ERK) signalling pathway. This down-regulation of KLF5 by EBER1 contributes to maintaining latent EBV infection in NPC. Furthermore, we uncovered the biological roles of KLF5 in NPC cells. Specifically, KLF5 may influence the cell cycle, prevent apoptosis, and encourage cell migration and proliferation - all of which have a generally pro-cancer impact. In conclusion, these findings offer novel strategies for EBV-positive NPC patients' antitumour treatment.

A nomogram based on nutritional and inflammatory parameters to predict DMFS and identify beneficiaries of adjuvant chemotherapy in IVA-stage nasopharyngeal carcinoma.

OBJECTIVE: This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy. METHODS: A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value. RESULTS: In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity. CONCLUSIONS: In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

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.

The Role of PTEN in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment.

Prodrug-conjugated tumor-seeking commensals for targeted cancer therapy.

Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%.

Targeting Cancer Mitochondria by Inducing an Abnormal Mitochondrial Unfolded Protein Response Leads to Tumor Suppression.

The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions. This study investigates the role of UPRmt in modulating the response of nasopharyngeal carcinoma cells to cisplatin-induced stress. We report that the inhibition of UPRmt via AEB5F exacerbates cisplatin cytotoxicity, as evidenced by increased lactate dehydrogenase (LDH) release and apoptosis, characterized by a surge in TUNEL-positive cells. Conversely, the activation of UPRmt with oligomycin attenuates these effects, preserving cell viability and reducing apoptotic markers. Immunofluorescence assays reveal that UPRmt activation maintains mitochondrial membrane potential and ATP production in the presence of cisplatin, countering the rise in reactive oxygen species (ROS) and inhibiting caspase-9 activation. These findings suggest that UPRmt serves as a cytoprotective mechanism in cancer cells, mitigating cisplatin-induced mitochondrial dysfunction and apoptosis. The data underscore the therapeutic potential of modulating UPRmt to improve the efficacy and reduce the side effects of cisplatin chemotherapy. This study provides a foundation for future research on the exploitation of UPRmt in cancer treatment, with the aim of enhancing patient outcomes by leveraging the cellular stress response pathways.

Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.

BACKGROUND: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. RESULTS: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. CONCLUSIONS: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.

Comprehensive analysis of recently discovered lncRNA-associated competing endogenous RNA network in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) arises from the epithelium of the nasopharynx and is characterized by geography-dependent incidence. Despite the high mortality rate, specifically in some ethnic groups, the mechanisms underlying NPC pathogenesis are not thoroughly understood and there is an urgent need to detect the potential and clinically applicable biomarkers to ameliorate the overall survival rate and improve the prognosis of patients. In recent years, research has increasingly focused on the importance of long non-coding RNAs (LncRNAs) in cancer progression. LncRNAs play critical roles in regulating gene expression through mechanisms such as competitively binding to microRNAs (CeRNA). While numerous LncRNAs have been studied in nasopharyngeal carcinoma (NPC), their potential as diagnostic and prognostic biomarkers have not been systematically examined. In the present study, we delve into elucidating the biological functions, molecular mechanisms, and clinical significance of newly identified LncRNAs that serve as sponges for different microRNAs in NPC. We highlight their regulatory mechanisms in promoting cell proliferation, invasion, and metastasis, and discuss their implications in diverse cancer-related signaling pathways. Our overall goal is to emboss the fundamental roles of LncRNA-mediated CeRNA networks in NPC progression, which may open up new avenues for determining the pathogenesis of NPC and developing effective prevention and treatment strategies.

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Prognostic Significance of Excision Repair Cross-Complementation Group 1 on Circulating Tumor Cells for Nasopharyngeal Carcinoma.

BACKGROUND: Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC. METHODS: We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed. RESULTS: The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001). CONCLUSION: Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

BackgroundLiquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC.MethodsWe retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed.ResultsThe positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001).ConclusionOur findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

Enhanced MRI Radiomics Based Model for Predicting Recurrence or Metastasis of Nasopharyngeal Cancer (NC) Undergoing Concurrent Chemoradiotherapy: A Retrospective Study.

Nasopharyngeal Carcinoma (NC) refers to the malignant tumor that occurs at the top and side walls of the nasopharyngeal cavity. The NC incidence rate always dominates the first among the malignant tumors of the ear, nose and throat, and mainly occurs in Asia. NC cases are mainly concentrated in southern provinces in China, with about 4 million existing NC. With the pollution of environment and pickled diet, and the increase of life pressure, the domestic NC incidence rate has reached 4.5-6.5/100000 and is increasing year by year. It was reported that the known main causes of NC include hereditary factor, genetic mutations, and EB virus infection, common clinical symptoms of NC include nasal congestion, bloody mucus, etc. About 90% of NC is highly sensitive to radiotherapy which is regard as the preferred treatment method; However, for NC with lower differentiation, larger volume, and recurrence after treatment, surgical resection and local protons and heavy ions therapy are also indispensable means. According to reports, the subtle heterogeneity and diversity exists in some NC, with about 80% of NC undergone radiotherapy and about 25% experienced recurrence and death within five years after radiotherapy in China. Therefore, screening the NC population with suspected recurrence after concurrent chemoradiotherapy may improve survival rates in current clinical decision-making.

NC is one of the prevalent malignancies of the head and neck region with poor prognosis. The aim of this study is to establish a predictive model for assessing NC prognosis using clinical and MR radiomics data.

FLI1 promotes IFN-γ-induced kynurenine production to impair anti-tumor immunity.

Nasopharyngeal carcinoma (NPC)-mediated immunosuppression within the tumor microenvironment (TME) frequently culminates in the failure of otherwise promising immunotherapies. In this study, we identify tumor-intrinsic FLI1 as a critical mediator in impairing T cell anti-tumor immunity. A mechanistic inquiry reveals that FLI1 orchestrates the expression of CBP and STAT1, facilitating chromatin accessibility and transcriptional activation of IDO1 in response to T cell-released IFN-γ. This regulatory cascade ultimately leads to augmented IDO1 expression, resulting in heightened synthesis of kynurenine (Kyn) in tumor cells. This, in turn, fosters CD8+ T cell exhaustion and regulatory T cell (Treg) differentiation. Intriguingly, we find that pharmacological inhibition of FLI1 effectively obstructs the CBP/STAT1-IDO1-Kyn axis, thereby invigorating both spontaneous and checkpoint therapy-induced immune responses, culminating in enhanced tumor eradication. In conclusion, our findings delineate FLI1-mediated Kyn metabolism as an immune evasion mechanism in NPC, furnishing valuable insights into potential therapeutic interventions.

Ethno-geographic distribution and histopathological classification of nasopharyngeal carcinoma in a single center in Nepal.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) shows geographic and ethnic variation with specific etiopathogenesis. This study characterized the distribution of NPC patients stratified by ethnicity, geography, and histology in a tertiary-level cancer center in Nepal. METHODS: A descriptive retrospective study was designed to analyze NPC cases from different regions among patients visiting the hospital from 2016 to 2021. Demographic and clinical information was obtained from medical records. Ethical approval was granted by the Nepal Health Research Council (NHRC). Data analyses and visualization were carried out with R software. RESULTS: During the six-year period, a total of 65 individuals were diagnosed with NPC, comprising 42 males and 23 females. Patient median age was 43 years (range 11-85 years). A bimodal age distribution of cases was observed with peaks in patients aged 30-39 years and 50-59 years. Of the NPC patients studied, 29 were from Koshi Province, with 7 cases from Ilam district and 6 cases from Morang district. There were 18 patients in Bagmati Province, and Kathmandu district had the highest number of cases within this region, with 8 patients. The highest proportion of cases were observed among patients of Janajati ethnicity (60%), including Rai, Limbu, and Sherpa people. Histologically, undifferentiated non-keratinizing NPC was the most commonly observed subtype, accounting for 43.1% of cases, followed by 20% differentiated non-keratinizing NPC and 4.6% keratinizing NPC across the entire sample population. The majority of patients (75.3%) were diagnosed at an advanced stage (stage III or IV) with none diagnosed at stage I. CONCLUSIONS: In our study, most cases of NPC occurred in patients from provinces in eastern Nepal (Koshi province), and of the Janajati ethnic community. The most common histological subtype was undifferentiated non-keratinizing carcinoma. Further epidemiological studies could address differences in prevalence and the challenge of late presentation of NPC patients in Nepal.

Comparative Proteomics Identified EXOSC1 as a Target Protein of Anticancer Peptide LVTX-8 in Nasopharyngeal Carcinoma Cells.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy that usually occurs among the nose and throat. Due to mild initial symptoms, most patients are diagnosed in the late stage, and the recurrence rate of tumors is high, resulting in many deaths every year. Traditional radiotherapy and chemotherapy are prone to causing drug resistance and significant side effects. Therefore, searching for new bioactive drugs including anticancer peptides is necessary and urgent. LVTX-8 is a peptide toxin synthesized from the cDNA library of the spider Lycosa vittata, which is consisting of 25 amino acids. In this study, a series of in vitro cell experiments such as cell toxicity, colony formation, and cell migration assays were performed to exam the anticancer activity of LVTX-8 in NPC cells (5-8F and CNE-2). The results suggested that LVTX-8 significantly inhibited cell proliferation and migration of NPC cells. To find the potential molecular targets for the anticancer capability of LVTX-8, high-throughput proteomic and bioinformatics analysis were conducted on NPC cells. The results identified EXOSC1 as a potential target protein with significantly differential expression levels under LVTX-8+/LVTX-8- conditions. The results in this research indicate that spider peptide toxin LVTX-8 exhibits significant anticancer activity in NPC, and EXOSC1 may serve as a target protein for its anticancer activity. These findings provide a reference for the development of new therapeutic drugs for NPC and offer new ideas for the discovery of biomarkers related to NPC diagnosis. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the data set identifier PXD050542.