Background. Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, the identification of the molecular mechanisms and the development of novel therapeutic strategies are important. Previous studies suggest that PNCK promotes tumor growth by suppressing PI3K/AKT/mTOR signaling in NPC. However, the underlying regulatory mechanism of PNCK for NPC invasion and metastasis remains unclear. Methods. The PNCK expression level was evaluated in nonmetastatic and metastatic NPC specimens by mRNA sequencing and immunohistochemistry. In vitro migration and invasion and in vivo nude mouse metastasis model and zebrafish model were used to evaluate the effects of PNCK ectopic expression on the metastatic ability of NPC cells. Gene set enrichment and western blot analyses were used to investigate the PNCK downstream signaling pathway. Results. Human metastatic NPC samples showed elevated PNCK expression at both mRNA and protein levels. Upregulated PNCK promoted in vitro NPC cell migration, invasion, and the formation of lung metastases; the vascular-labeled fluorescence signal increased in the in vivo zebrafish model. Mechanistically, pathway analysis showed that the upregulation of PNCK may promote cell metastasis by activating the NF-κB/VEGF signaling pathway. Conclusions. These findings revealed the specific critical role of PNCK in promoting NPC metastasis and angiogenesis, which suggested that PNCK may have implications as a potential therapeutic target for individualized NPC treatment.

Early screening and precise staging are crucial for reducing mortality in patients with nasopharyngeal carcinoma (NPC). This study aimed to assess the performance of blood protein surface-enhanced Raman scattering (SERS) spectroscopy, combined with deep learning, for the precise detection of NPC. A highly efficient protein SERS analysis, based on a membrane purification technique and super-hydrophobic platform, was developed and applied to blood samples from 1164 subjects, including 225 healthy volunteers, 120 stage I, 249 stage II, 291 stage III, and 279 stage IV NPC patients. The proteins were rapidly purified from only 10 µL of blood plasma using the membrane purification technique. Then, the super-hydrophobic platform was prepared to pre-concentrate tiny amounts of proteins by forming a uniform deposition to provide repeatable SERS spectra. A total of 1164 high-quality protein SERS spectra were rapidly collected using a self-developed macro-Raman system. A convolutional neural network-based deep-learning algorithm was used to classify the spectra. An accuracy of 100% was achieved for distinguishing between the healthy and NPC groups, and accuracies of 96%, 96%, 100%, and 100% were found for the differential classification among the four NPC stages. This study demonstrated the great promise of SERS- and deep-learning-based blood protein testing for rapid, non-invasive, and precise screening and staging of NPC.

Background The landscape of the tumor microenvironment (TME) is intricately linked to the development of head and neck squamous cell carcinoma (HNSCC) and significantly influences immunotherapy efficacy. Recent research has underscored the pivotal role of PNCK in cancer progression, yet its relationship with immunotherapy remains elusive. Methods We leveraged sequencing data from our cohort and public databases to evaluate PNCK expression, prognostic significance, and immune efficacy prediction. In vitro and in vivo experiments explored the role of PNCK in HNSCC progression. Animal models assessed the therapeutic effects and survival benefits of PNCK knockdown combined with immune checkpoint inhibitors (ICIs). Single-cell transcriptomics analyzed the impact of PNCK on the TME, and proteomic studies elucidated the mechanisms. Results PNCK exerts multifaceted critical roles in the progression of HNSCC. Lower PNCK expression is associated with improved prognosis, enhanced immune cell infiltration, and increased responsiveness to ICIs. Conversely, PNCK promotes HNSCC cell migration, invasion, proliferation, colony formation, zebrafish angiogenesis, and tumor growth in mice. Moreover, targeting PNCK enhances sensitivity to ICIs and leads to significant alterations in the T-cell and B-cell ratios within the TME. These changes are attributed to the inhibition of nuclear transcription of PNCK-phosphorylated ZEB1, which restricts cytokine release and inflames the immune microenvironment to regulate the TME. Conclusions Inhibition of PNCK may be a potential strategy for treating HNSCC, as it may activate the immune response and improve the TME, thereby enhancing the efficacy of immunotherapy for HNSCC patients.

Purpose: The prognosis of head and neck squamous cell carcinoma (HNSCC) is poor. Necroptosis is a novel programmed form of necrotic cell death. The prognostic value of necroptosis-associated lncRNAs expression in HNSCC has not been explored.Methods: We downloaded mRNA expression data of HNSCC patients from TCGA databases. Prognostic lncRNAs were identified by univariate Cox regression. LASSO was used to establish a model with necroptosis-related lncRNAs. Kaplan-Meier analysis and ROC were applied to verify the model. Finally, functional studies including gene set enrichment analyses, immune microenvironment analysis, and anti-tumor compound IC50 prediction were performed.Results: We identified 1,117 necroptosis-related lncRNAs. The Cox regression showed 55 lncRNAs were associated with patient survival (p < 0.05). The risk model of 24- lncRNAs signature categorized patients into high and low risk groups. The patients in the low-risk group survived longer than the high-risk group (p < 0.001). Validation assays including ROC curve, nomogram and correction curves confirmed the prediction capability of the 24-lncRNA risk mode. Functional studies showed the two patient groups had distinct immunity conditions and IC50.Conclusion: The 24-lncRNA model has potential to guide treatment of HNSCC. Future clinical studies are needed to verify the model.

Nasopharyngeal carcinoma (NPC) remains a major healthcare burden in endemic regions, and locally advanced disease demands optimal radiotherapy for curative intent. Although both Volumetric Modulated Arc Therapy (VMAT) and tomotherapy (TOMO) are both advanced conformal radiotherapy techniques, their comparative efficacy in locally advanced NPC has not been fully clarified by large-scale studies that adequately control for selection bias. This study compared the therapeutic efficacy and safety of VMAT versus TOMO in patients with locally advanced NPC. We performed a retrospective cohort study of 1,974 patients with histologically confirmed locally advanced NPC treated at our institution between January 2016 and December 2019. Patients received either VMAT (n = 1,720) or TOMO (n = 254) combined with systemic therapy per institutional protocols. To reduce selection bias, propensity score matching (PSM) was conducted at a 1:1 ratio using nearest-neighbor matching without replacement, with a 0.2 standard deviation caliper to balance baseline characteristics between groups. Primary endpoints included overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). The secondary endpoints were treatment response rates and treatment-related adverse events. After PSM, 979 patients were included in the final analysis (728 VMAT and 251 TOMO). Standardized mean differences (SMDs) for all baseline variables were < 0.1, confirming adequate balance between groups. With a median follow-up of 42 months, no significant differences in the 3-year survival rates were observed between the VMAT and TOMO groups: OS (85.2% vs. 87.1%, P = 0.645), PFS (78.9% vs. 81.2%,P = 0.391), LRFS (91.3% vs. 93.1%, P = 0.505), and DMFS (85.7% vs. 87.4%, P = 0.383). Both techniques achieved high overall response rates (ORR) (96.7% vs. 97.6%, p = 0.418). For safety, xerostomia occurred significantly less frequently in the TOMO group (33.86% vs. 46.84%, p < 0.001), consistent with its superior ability to spare parotid glands, while other adverse events showed no significant intergroup differences. VMAT and TOMO yield comparable therapeutic efficacies in patients with locally advanced NPC. Both advanced radiotherapy techniques are effective options in multimodality care. The choice between them should be based on institutional capacity and patient-specific factors, including quality-of-life needs and target volume anatomy, rather than anticipated survival benefits.