Marker For Nasopharyngeal Carcinoma Research Articles

Metachronous Second Primary in the Form of Nasopharyngeal Carcinoma Following Treatment of Small Cell Neuroendocrine Carcinoma of the Head and Neck: Dual Tracer PET/CT Findings Highlighting SSTR2 Expression and Its Theranostic Implications

AbstractPatients of head and neck squamous cell carcinoma (HNSCC) experience increased risk of developing second primary cancer (SPC) necessitating active surveillance during their disease course. SPCs are associated with poor prognosis and are the leading cause of long-term morbidity and mortality impacting survival of patients with HNSCC. Small cell neuroendocrine carcinoma (SmNEC) is a rare but aggressive neoplasm with poor prognosis and high risk of local recurrence and distant metastasis. We report an exceedingly rare case of nasopharyngeal carcinoma (NPC) presenting as a recurrence in the form of metachronous second primary to primary SmNEC 9 years after chemotherapy. The dual tracer positron emission tomography and computed tomography (PET/CT) imaging approach ([68Ga]Ga-DOTATATE-PET/CT with 18F-FDG-PET/CT) was explored in such metachronous NPCs, and the findings are illustrated with its potential for theranostic applications. NPC is a rare malignancy with significant geographical variations in incidence rates. Somatostatin receptor 2 (SSTR2) expression in NPC is well documented and can serve as a potential theragnostic marker in advanced NPC where the successful outcome is minimal with currently available treatment modalities.

Serum inflammatory markers as prognostic marker for nasopharyngeal carcinoma with liver metastasis: a multi-center retrospective study.

This retrospective study investigated the prognostic value of serum inflammatory markers in nasopharyngeal carcinoma (NPC) patients, focusing on their association with overall survival (OS) and liver metastasis-free survival (LMFS). The study included 314 NPC patients treated between 2010 and 2020. Clinical characteristics, treatment methods, and serum inflammatory markers were assessed. Patients were categorized into two groups of with and without liver metastasis. Univariate and multivariate Cox regression and Kaplan-Meier survival analyses were performed to investigate the prognostic value of serum inflammatory markers in NPC patients with and without liver metastasis. In the whole cohort, univariate Cox regression analysis singled out tumor necrosis factor-α (TNF-α) (HR = 1.57, 95% CI 1.44-4.90, p = 0.004) and neutrophil-to-lymphocyte ratio (NLR) (HR = 2.13, 95% CI 1.33-3.99, p = 0.009), which were significantly associated with poorer OS. In patients with liver metastasis, TNF-α and NLR could not independently predict OS. However, high TNF-α levels were independently associated with worse OS in patients without liver metastasis (HR (95% CI) = 2.75 (1.67-8.68), p < 0.001). High NLR levels could independently predict poor OS in both groups with (HR (95% CI) = 1.94 (1.77-6.38), p = 0.010) and without liver metastasis (HR (95% CI) = 1.58 (1.19-7.54), p = 0.009). Ultimately, TNF-α and NLR could not significantly predict LMFS. This study highlights the prognostic significance of TNF-α and NLR in NPC patients, especially in those with liver metastasis. These inflammatory markers could serve as valuable indicators for assessing the prognosis of NPC patients. Further research is warranted to validate their clinical utility and explore potential therapeutic implications.

PICK1 inhibits the malignancy of nasopharyngeal carcinoma and serves as a novel prognostic marker

Although many important advances have been made in the treatment of nasopharyngeal carcinoma (NPC) in recent years, local recurrence and distant metastasis remain the main factors affecting NPC prognosis. Biomarkers for predicting the prognosis of NPC need to be urgently identified. Here, we used whole-exon sequencing (WES) to determine whether PICK1 mutations are associated with the prognosis of NPC. Functionally, PICK1 inhibits the proliferation and metastasis of NPC cells both in vivo and in vitro. Mechanistically, PICK1 inhibited the expression of proteins related to the Wnt/β-catenin signaling pathway. PICK1 restrained the nuclear accumulation of β-catenin and accelerated the degradation of β-catenin through the ubiquitin-proteasome pathway. The reduced PICK1 levels were significantly associated with poor patient prognosis. Hence, our study findings reveal the mechanism by which PICK1 inactivates the Wnt/β-catenin signaling pathway, thereby inhibiting the progression of NPC. They support PICK1 as a potential tumor suppressor and prognostic marker for NPC.

AI-Based Risk Score from Tumour-Infiltrating Lymphocyte Predicts Locoregional-Free Survival in Nasopharyngeal Carcinoma.

Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein-Barr virus DNA, are not sensitive to locoregional recurrence. We gathered 385 whole-slide images (WSIs) from haematoxylin and eosin (H&E)-stained NPC sections (n = 367 cases), which were collected from Sun Yat-sen University Cancer Centre. We developed a deep learning algorithm to detect tumour nuclei and lymphocyte nuclei in WSIs, followed by density-based clustering to quantify the tumour-infiltrating lymphocytes (TILs) into 12 scores. The Random Survival Forest model was then trained on the TILs to generate risk score. Based on Kaplan-Meier analysis, the proposed methods were able to stratify low- and high-risk NPC cases in a validation set of locoregional recurrence with a statically significant result (p < 0.001). This finding was also found in distant metastasis-free survival (p < 0.001), progression-free survival (p < 0.001), and regional recurrence-free survival (p < 0.05). Furthermore, in both univariate analysis (HR: 1.58, CI: 1.13-2.19, p < 0.05) and multivariate analysis (HR:1.59, CI: 1.11-2.28, p < 0.05), we also found that our methods demonstrated a strong prognostic value for locoregional recurrence. The proposed novel digital markers could potentially be utilised to assist treatment decisions in cases of NPC.

C2orf48 promotes the progression of nasopharyngeal carcinoma by regulating high mobility group AT-hook 2.

Recurrence and metastasis are the major factors affecting the survival of nasopharyngeal carcinoma (NPC), and the mechanism remains unclear. Long non-coding RNA chromosome 2 open reading frame 48 (C2orf48) has been shown to influence the prognosis of many cancers. However, C2orf48's function in NPC has not been clarified. In this investigation, C2orf48 expression in NPC was measured by quantitative real-time PCR (qRT-PCR) at the cellular and tissue levels, and the association between C2orf48 expression and the prognosis of patients with NPC was examined. Additionally, the effects of C2orf48 and high mobility group AT-hook 2 (HMGA2) upon NPC proliferation, migration, and invasion were examined employing the MTT assay, colony formation assay, and transwell assay, respectively. Furthermore, the association between C2orf48 and HMGA2 in NPC was investigated. Our research demonstrated that C2orf48 was overexpressed in NPC tissues and cell lines, and compared to patients with lower levels of C2orf48 expression, those with higher levels had poorer 5-year overall survival and progression-free survival. Functionally, C2orf48 overexpression accelerated NPC cells proliferation, migration, and invasion. Besides, the tandem mass tag (TMT) quantitative proteomic analysis indicated that HMGA2 may be a target of C2orf48. Moreover, upregulation of C2orf48 could increase HMGA2 expression, and HMGA2 silencing could counteract the proliferation, migration, and invasion changes induced by C2orf48 in NPC cells. These results reveal that overexpression of C2orf48 can promote NPC cells proliferation, migration, and invasion via regulating the expression of HMGA2 and C2orf48 may be a potentially important prognostic marker for NPC.

Multi-omics analysis reveals the association between elevated KIF18B expression and unfavorable prognosis, immune evasion, and regulatory T cell activation in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. The expression profile and functions of kinesin family member 18B (KIF18B) remain unclear in NPC. Bulk and single-cell transcriptome data for NPC were downloaded. KIF18B expression differences in NPC and normal tissues and its prognostic value were validated by immunohistochemistry and Cox model. We performed multi-faceted functional enrichment analysis on KIF18B. Immune infiltration was analyzed comprehensively by the CIBERSORT, EPIC, and quanTIseq algorithms and the BisqueRNA package and confirmed by immunofluorescence assay. The intercellular communication were investigated by the CellChat package. We explored the dynamics of KIF18B expression by pseudotime trajectory. M6A modification analysis rely on SRAMP platform. The treatment response were evaluated by Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore and IC50 value. KIF18B overexpression in NPC led to unfavorable prognosis, and significantly associated with advanced T, N, and stage classifications. Functional analysis demonstrated that KIF18B was involved in immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification and therapeutic responses. The deconvolution algorithm indicated that activated regulatory T cells (Tregs) had the strongest positive correlation with KIF18B among immune cells (R = 0.631). Validated by immunofluorescence assay, the high KIF18B expression group displayed a notable rise in Tregs infiltration, accompanied by a substantial decrease in the infiltration of CD8+ T cells and macrophages. In the intercellular communication network, malignant cells with high KIF18B expression implicated in more interactions, and activated and recruited Tregs by modulating cytokines, chemokines, and immune checkpoints. KIF18B was upregulated in more advanced malignant cells and influenced EMT by regulating ITGA6, VIM, and ZEB1/2. KIF18B expression was positively related to m6A "writer" and "reader" genes, and negatively related to "eraser" genes. The KIF18B high expression group exhibited a higher TIDE score and elevated IC50 values for the commonly used chemotherapy drugs, gemcitabine, oxaliplatin, and 5-fluorouracil. KIF18B is a significant prognostic marker in NPC, and may modulate immune evasion and EMT. M6A modification may account for the aberrant overexpression of KIF18B in NPC. Furthermore, KIF18B may predict response to immunotherapy and chemotherapy.

SYNPO2 upregulation is an unfavorable prognostic factor for nasopharyngeal carcinoma patients.

Nasopharyngeal carcinoma (NPC) is the most common malignant neoplasm of the nasopharynx. Despite improvements in the clinical treatment strategies for NPC, NPC patients usually have poor survival rates because of late diagnosis, tumor metastasis, and recurrence. Therefore, the identification of potential diagnostic and prognostic markers for NPC is imperative. We investigated the differential expression of cell adhesion-related genes (gene ontology:0003779) and tumorigenesis-related genes (GSE12452) in patients with NPC. The correlations between synaptopodin-2 (SYNPO2) immune expression and clinicopathological features were analyzed using Pearson chi-square test. Multivariate analysis was performed using Cox proportional hazards model. SYNPO2 expression was significantly higher in NPC tumor tissues than in nontumor tissues. High SYNPO2 expression was significantly associated with the advanced disease stage (P = .006). Univariate analysis showed that high expression of SYNPO2 was associated with poor disease-specific survival, distal metastasis-free survival, and local recurrence-free survival in patients with NPC. Notably, our multivariate analysis demonstrated that high SYNPO2 expression was substantially correlated with inferior disease-specific survival (hazard ratio = 1.968, P = .012) and local recurrence-free survival (hazard ratio = 3.386, P = .001). Overall, our findings reveal that SYNPO2 may aid in the development of potential prognostic biomarkers for NPC patients.

ZIC2 induces pro-tumor macrophage polarization in nasopharyngeal carcinoma by activating the JUNB/MCSF axis

Nasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor of the head and neck that often exhibits local recurrence and distant metastasis. The molecular mechanisms are understudied, and effective therapeutic targets are still lacking. In our study, we found that the transcription factor ZIC2 was highly expressed in NPC. Although ZIC family members play important roles in neural development and carcinogenesis, the specific mechanism and clinical significance of ZIC2 in the tumorigenesis and immune regulation of NPC remain elusive. Here, we first reported that high expression of ZIC2 triggered the secretion of MCSF in NPC cells, induced M2 polarization of tumor-associated macrophages (TAMs), and affected the secretion of TAM-related cytokines. Mechanistically, ChIP-seq and RNA-seq analyses identified JUNB as a downstream target of ZIC2. Furthermore, ZIC2 was significantly enriched in the promoter site of JUNB and activated JUNB promoter activity, as shown by ChIP-qPCR and luciferase assays. In addition, JUNB and MCSF participated in ZIC2-induced M2 TAMs polarization. Thus, blocking JUNB and MCSF could reverse ZIC2-mediated M2 TAMs polarization. Moreover, Kaplan-Meier survival analyses indicated that high expression of ZIC2, JUNB, and CD163 was positively associated with a poor prognosis in NPC. Overexpression of ZIC2 induced tumor growth in vivo, with the increase of JUNB, MCSF secretion, and CD163. In summary, our study implies that ZIC2 induces M2 TAM polarization, at least in part through regulation of JUNB/MCSF and that ZIC2, JUNB, and CD163 can be utilized as prognostic markers for NPC and as therapeutic targets for cancer immunotherapy.

Methylated tumor suppressor gene SCARA5 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma.

Background: SCARA5 may play an important role in nasopharyngeal carcinoma. Materials & methods: PCR and immunohistochemistry were used to detect the expression and promoter methylation of SCARA5. Cell proliferation assays, spheroid culture, flow cytometry analysis, Transwell assays and xenotransplantation tests were utilized to determine the functional effects of SCARA5. RNA-sequencing, western blotting, immunofluorescence and dual-luciferase reporter assays were used to assess SCARA5-mediated outcomes. Results: SCARA5 was downregulated by promoter methylation. Overexpression of SCARA5 inhibited cell migration, invasion and proliferation. SCARA5 enhanced nasopharyngeal carcinoma cell sensitivity to chemotherapy with cisplatin and 5-fluorouracil. SCARA5 drives tumor apoptosis by downregulating HSPA2. Conclusion: SCARA5 may be a useful clinical marker innasopharyngeal carcinoma.

Lipocalin-2 Upregulation in Nasopharyngeal Carcinoma: A Novel Potential Diagnostic Biomarker.

Lipocalin-2 (LCN2) deregulation has been reported in several types of cancer and is implicated in the proliferation, migration, angiogenesis, and progression of tumors. However, its aberrant expression has been rarely studied in nasopharyngeal carcinoma (NPC). In the present study, we investigated the expression of LCN2 in NPC patients. In this descriptive cross-sectional study, 29 NPC and 20 non-cancerous control paraffin pathology blocks were obtained from the seven-year (2011 to 2018) archive of Razi Laboratory in Rasht, Iran. LCN2 mRNA expression was evaluated through quantitative real-time PCR. In addition, immunohistochemistry was performed to evaluate LCN2 expression at the protein level. The fold change value and total immunostaining score (TIS) were applied for quantitative evaluation. The nonparametric Mann-Whitney U test and Fisher's exact test were used through GraphPad Prism 8.3.0 software. P<0.05 was considered statistically significant. Our results revealed that LCN2 mRNA and protein levels in NPC tissues were significantly higher than control tissues (P=0.028 and P=0.002, respectively). At the protein level, 65.51% (19/29) of NPC patients were categorized as having high LCN2 expression (TIS>3) and 34.47% (10/29) as low expression (TIS≤3). While in the control group, 25% (5/20) of subjects represented a high expression of LCN2 (TIS>3), and 75% (15/20) showed no or weak expression (TIS≤3). No significant correlation was found between the overexpression of LCN2 at the protein level and the demographic features of the patients. Our findings suggest that LCN2 might be considered a potential new diagnostic marker for NPC. However, this warrants further studies.

Development of a Duplex Serological Multiplex Assay for the Simultaneous Detection of Epstein-Barr Virus IgA and IgG Antibodies in Nasopharyngeal Carcinoma Patients.

Epstein-Barr virus (EBV) IgA and IgG antibodies in serum from nasopharyngeal carcinoma (NPC) patients are well-established markers for EBV-positive NPC. Luminex-based multiplex serology can analyze antibodies to multiple antigens simultaneously; however, the detection of both IgA and IgG antibodies requires separate measurements. Here we describe the development and validation of a novel duplex multiplex serology assay, which can analyze IgA and IgG antibodies against several antigens simultaneously. Secondary antibody/dye combinations, as well as serum dilution factors, were optimized, and 98 NPC cases matched to 142 controls from the Head and Neck 5000 study (HN5000) were assessed and compared to data previously generated in separate IgA and IgG multiplex assays. EBER in situ hybridization (EBER-ISH) data available for 41 tumors was used to calibrate antigen-specific cut-offs using receiver operating characteristic (ROC) analysis with a prespecified specificity of ≥90%. A directly R-Phycoerythrin-labeled IgG antibody in combination with a biotinylated IgA antibody and streptavidin-BV421 reporter conjugate was able to quantify both IgA and IgG antibodies in a duplex reaction in a 1:1000 serum dilution. The combined assessment of IgA and IgG antibodies in NPC cases and controls from the HN5000 study yielded similar sensitivities as the separate IgA and IgG multiplex assays (all > 90%), and the duplex serological multiplex assay was able to unequivocally define the EBV-positive NPC cases (AUC = 1). In conclusion, the simultaneous detection of IgA and IgG antibodies provides an alternative for the separate IgA/IgG antibody quantification and may present a promising approach for larger NPC screening studies in NPC endemic areas.

Thyroid dysfunction in Chinese nasopharyngeal carcinoma after anti-PD-1 therapy and its association with treatment response

BackgroundProgrammed cell death protein-1 (PD-1) blockade therapies have demonstrated efficacy in nasopharyngeal carcinoma (NPC). Thyroid dysfunction is among the most common immune-related adverse events. This study aimed to explore the clinical pattern of thyroid dysfunction and its relationship with survival marker in nonmetastatic NPC after immunotherapy.MethodsFrom January 1, 2019, to December 31, 2021, 165 pairs of nonmetastatic NPC patients (165 with and 165 without anti-PD-1 immunotherapy) matched by the propensity score matching method were included in this study. Thyroid function was assessed retrospectively before the first treatment and during each immunotherapy cycle.ResultsThe spectrum of thyroid dysfunction was different between the immunotherapy and control groups (P < 0.001). Compared with the control group, patients in the immunotherapy group developed more hypothyroidism (14.545% vs. 7.273%), less hyperthyroidism (10.909% vs. 23.636%), and a distinct pattern, biphasic thyroid dysfunction (3.030% vs. 0%). Immunotherapy also accelerates the onset of hypothyroidism, which was earlier with a median onset time difference of 32 days (P < 0.001). Patients who acquired thyroid dysfunction during immunotherapy had better complete biological response to treatment (OR, 10.980; P = 0.042).ConclusionsFor nonmetastatic NPC, thyroid dysfunction was associated with better response to treatment in immunotherapy but not in routine treatment. Thyroid function could be used as a predictor for survival and should be under regular and intensive surveillance in clinical practice of anti-PD-1 immunotherapy for nonmetastatic NPC.

Upregulated Long Non-coding RNA Lnc-MRPL39-2:1 Induces the Growth and Invasion of Nasopharyngeal Carcinoma by Binding to HuR and Stabilizing β-Catenin mRNA.

Long non-coding RNAs (lncRNAs) have been to regulate tumor progression and therapy resistance through various molecular mechanisms. In this study, we investigated the role of lncRNAs in nasopharyngeal carcinoma (NPC) and the underlying mechanism. Using lncRNA arrays to analyze the lncRNA profiles of the NPC and para-tumor tissues, we detected the novel lnc-MRPL39-2:1, which was validated by in situ hybridization and by the 5' and 3' rapid amplification of the cDNA ends. Further, its role in NPC cell growth and metastasis was verified in vitro and in vivo. The researchers conducted the RNA pull-down assays, mass spectrometry (MS), dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, and the MS2-RIP assays were then used to identify the lnc-MRPL39-2:1-interacting proteins and miRNAs. We found that lnc-MRPL39-2:1, which was highly expressed in in NPC tissues, was related to a poor prognosis in NPC patients. Furthermore, lnc-MRPL39-2:1 was shown to induce the growth and invasion of NPC by interacting directly with the Hu-antigen R (HuR) to upregulate β-catenin expression both in vivo and in vitro. Lnc-MRPL39-2:1 expression was also suppressed by microRNA (miR)-329. Thus, these findings indicate that lnc-MRPL39-2:1 is essential in NPC tumorigenesis and metastasis and highlight its potential as a prognostic marker and therapeutic target for NPC.

The valuable role of dynamic 18F FDG PET/CT-derived kinetic parameter [formula omitted] in patients with nasopharyngeal carcinoma prior to radiotherapy: A prospective study

Background and PurposeDynamic positron emission tomography/computed tomography (PET/CT) served the potential role of characterizing malignant foci. The main objective of this prospective study was to explore the advantage of dynamic PET/CT imaging in characterizing nasopharyngeal carcinoma (NPC). Methods and MaterialsPatients with probable head and neck disease underwent a local dynamic PET/CT scan followed by a whole-body static scan. Patlak analysis was used to generate parametric influx rate constant (Ki) images from 48 frames obtained from a dynamic PET/CT scan. By delineating the volumes-of-interest (VOIs) of: primary tumor (PT), lymph node (LN), and normal nasopharyngeal tissues (N), we acquired the corresponding Ki mean and SUVmean of each site respectively to perform the quantitative statistical analysis. ResultsQualified images of 71 patients with newly diagnosed NPC and 8 without nasopharyngeal malignant lesions were finally included. We found the correlations between Ki mean-PT and critical clinical features, including clinical stage (r = 0.368), T category (r = 0.643) and EBV-DNA copy status (r = 0.351), and Ki mean-PT differed within the group. SUVmean-PT showed correlations with clinical stage (r = 0.280) and T category (r = 0.472), but could hardly differ systematically within group of clinical features except T category. Ki mean-LN offered the positive correlations with N category (r = 0.294), M category (r = 0.238) and EBV-DNA copy status (r = 0.446), and differed within the group. In addition, Ki mean represented a sensitivity of 94.4 % and a specificity of 100 %, in distinguishing NPC from the non-NPC, when the cut-off was defined as 0.0106. When the cut-off of SUV being defined as 2.03, the sensitivity and specificity were both 100 %. ConclusionOur research confirmed Ki compared favorably to SUV in characterizing NPC and found that Ki can serve as an effective imaging marker of NPC.

Differentially Infiltrated Identification of Novel Diagnostic Biomarkers Associated with Immune Infiltration in Nasopharyngeal Carcinoma.

The prognostic value of tumor-infiltrating immune cells has been widely studied in nasopharyngeal carcinoma (NPC). However, the role of tumor-infiltrating immune cells in the diagnosis of NPC has not been fully elucidated. Thus, tumor-infiltrating immune cell-related biomarkers in the diagnosis of NPC patients were explored in the current study. Gene expression profiles of NPC patients were downloaded from the Gene Expression Omnibus (GEO) database. Differentially infiltrating immune cells (DDICs) between NPC and control samples were analyzed by the CIBERSORT algorithm. Weighted gene coexpression network analysis (WGCNA) was performed to screen hub genes significantly correlated with DDIC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of hub genes were performed with R package clusterProfiler. The diagnostic value of hub genes was evaluated by receiver operating characteristic (ROC) curves. RT-qPCR was conducted to validate the expression patterns of diagnostic markers in NPC and adjacent control tissues. The correlations between diagnostic markers and immunomodulators were analyzed using the TISIDB. The protein-protein interaction (PPI) network based on immunomodulators significantly associated with diagnostic biomarkers was constructed and visualized by STRING. The functional enrichment analysis of genes in the PPI network was analyzed by the WebGestalt online tool. The abundances of memory B cells, plasma cells, follicular helper T cells, activated NK cells, M0 macrophages, M1 macrophages, M2 macrophages, resting mast cells, and activated mast cells were significantly different between NPC and control samples. Dark orange was identified as the hub module, with a total of 371 genes associated with memory B cells, plasma cells, and M0 and M1 macrophages defined as hub genes, which were enriched into immune-related biological processes and pathways. FCER2, KHDRBS2, and IGSF9 were considered diagnostic biomarkers with areas under ROC curves as 0.985, 0.978, and 0.975, respectively. Moreover, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) suggested that the expression patterns of FCER2, KHDRBS2, and IGSF9 were consistent with the results in GEO datasets. TISIDB analysis revealed that FCER2, KHDRBS2, and IGSF9 had a strong association with 8 immunoinhibitors (BTLA, CD160, CD96, LAG3, PDCD1, TIGIT, CD244, and TGFB1) and 11 immunostimulators (CD27, CD28, CD40LG, CD48, ICOS, KLRC1, KLRK1, TMIGD2, TNFRSF13C, CXCR4, and C10 or f54). The PPI network implied that these 19 immunomodulators had interactions with other 50 genes. WebGestalt analysis demonstrated that 69 genes in the PPI network were enriched into cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and pathways in cancer. Our study identified novel diagnostic biomarkers and revealed potential immune-related mechanisms in NPC. These findings enlighten the investigation of the molecular mechanisms of tumor-infiltrating immune cells regulating NPC.

TRIM11, a new target of p53, facilitates the migration and invasion of nasopharyngeal carcinoma cells

BackgroundAlthough tripartite motif-containing protein 11 (TRIM11) is known to be associated with a variety of cancers, its role in nasopharyngeal carcinoma (NPC) is unclear.Methods and resultsTo investigate the role of TRIM11 in NPC, TRIM11 was stably overexpressed in 6–10B and CNE2 cells with lentiviral vectors and knocked down in S18 and 5–8F cells using the CRISPR/Cas9 system. Transwell assays and wound-healing assays revealed that TRIM11 facilitated the migration and invasion of NPC cells. Mechanistically, we found that p53 inhibits TRIM11 expression by binding to its promoter.ConclusionsTRIM11 may serve as a potential diagnostic marker for NPC and has a certain therapeutic value.

Long non-coding RNA RGMB-AS1 represses nasopharyngeal carcinoma progression via binding to forkhead box A1

ABSTRACT Long non-coding RNA RGMB-AS1 (RGMB antisense RNA 1) plays a crucial role in tumor progression. However, its underlying mechanism in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we analyzed the clinical significance of lncRNA RGMB-AS1 as a possible potential marker in NPC, and investigated the effect and mechanism of lncRNA RGMB-AS1 on proliferation, migration and epithelial mesenchymal transformation (EMT) of NPC by directly binding Forkhead box A1 (FOXA1) in vitro and in vivo. In conclusion, LncRNA RGMB-AS1 inhibits malignant behaviors and EMT by regulating FOXA1, and lncRNA RGMB-AS1 may be an important indicator of clinical prognosis.

Protein C receptor maintains cancer stem cell properties via activating lipid synthesis in nasopharyngeal carcinoma

Metastasis and recurrence account for 95% of deaths from nasopharyngeal carcinoma (NPC). Cancer stem cells (CSCs) are regarded as one of the main reasons for tumor cell resistance to clinical therapy, and cancer metastasis or recurrence, while little is known about CSCs in NPC. The present study uncovers a subpopulation of cells labeled as CD45−EPCAM+PROCR+ in NPC biopsy samples that exhibit stem cell-like characteristics. A relatively low number of these cells initiate xenograft tumors in mice. Functional analysis reveals that protein C receptor (PROCR) not only serves as a stem cell marker in NPC, but also maintains tumor cells’ stemness potential through regulating lipid metabolism and mitochondrial fission. Epistatic studies reveal that cAMP-protein kinase A stimulates Ca2+ release to manipulate lipid metabolism related genes’ expression. Finally, in a cohort of 207 NPC samples, PROCR expression is correlated with tumor metastasis or recurrence, and predicts poor prognosis. These novel findings link PROCR labeled CSCs with lipid metabolism and mitochondrial plasticity, and provides new clinical target against metastatic or recurrent NPC.

Nasopharyngeal carcinoma patients from Norway show elevated Epstein-Barr virus IgA and IgG antibodies prior to diagnosis

BackgroundIgA antibodies against few Epstein-Barr virus (EBV) proteins are established serological markers for nasopharyngeal carcinoma (NPC). We recently validated a novel, comprehensive EBV marker panel and showed that IgA, but also IgG antibodies against multiple EBV proteins are highly sensitive and specific for EBV-positive NPC at diagnosis. However, data about these novel biomarkers as prospective markers for NPC are sparse. MethodsThis study included 30 incident NPC cases and 60 matched controls from the Norwegian Janus Serum Bank. For 21 NPCs, molecular EBV and human papillomavirus (HPV) status were assessed by EBER-ISH and HPV DNA/RNA testing by PCR, respectively. IgA and IgG serum antibodies against 17 EBV antigens were analyzed in prediagnostic sera of cases (median lead time 14 years) and controls using multiplex serology. Sensitivities were calculated using receiver operating characteristic analysis pre-specified to yield 90% specificity in the control group. From 10 cases, serial samples were available. ResultsQuantitative EBV antibody levels were significantly elevated among all cases (p < 0.05) for three IgA and six IgG antibodies. The highest sensitivities for defining 12 EBER-ISH-positive NPCs were observed for BGLF2 IgA (67%) and BGLF2 IgG (83%). Increased IgA and IgG antibody levels between the first and last draw before diagnosis were observed for EBER-ISH positive, but not for EBER-ISH negative NPCs. Among 21 molecularly analyzed NPCs, 4 EBER-ISH negative NPCs showed concomitant positivity to HPV type-specific DNA and RNA; 3 NPCs were HPV16 and 1 NPC was HPV18 positive. ConclusionBoth, EBV IgA and IgG antibody levels are significantly elevated many years before diagnosis of EBV-positive NPCs in Norway, an NPC low-incidence region. This study provides insights into one of the largest available prospective sample collections of NPCs in a non-endemic country.

A Clinical Update on the Prognostic Effect of microRNA Biomarkers for Survival Outcome in Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

Simple SummaryCurrent estimates by GLOBOCAN now incorporate NPC as a malignancy discrete from other head and neck malignancies among the 36 disease locales assessed. Based on the latest report, the global cancer burden is estimated to have risen to 19.3 million new cases, and 9.6 million malignancies were recorded in 2020 throughout the world. The study has clinical implications and could improve treatment decision-making and post-treatment care. The study could also motivate future clinical research and development in the arena of NPC prognostic biomarkers.ve men and one in every six women develops cancer during their lifetime, and one out of eight men and one in every 11 women progresses to chronic stage. The study has clinical implications and could improve treatment decision-making and post-treatment care. The study could also motivate future clinical research and development in the arena of NPC prognostic biomarkers.Background: Nasopharyngeal carcinoma (NPC), a relatively uncommon malignancy in the Western world, is highly prevalent in Southeast Asia where the treatment outcomes are poor. Despite recent improvements in diagnosis and treatment locoregional control, distant metastasis and chemoresistance continue to be a significant cause of mortality. Identification of a reliable and comprehensive prognostic biomarker is highly desirable. The potential relevance of microRNAs (miRNAs) as prognostic markers in NPC is assessed in this systematic review and meta-analysis. Methods: A systematic review was performed using the PubMed and Science Direct databases. The search was limited to search results between 2018 and 2020 with the keywords and search strings developed as per the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The recovered articles were carefully screened based on the selection criteria. In the meta-analysis study, high and low expression levels of miRNAs were measured using the hazard ratio (HR) and 95 percent confidence interval (CI) for patients’ survival outcomes. Egger’s bias indicator test and funnel plot symmetry were used to assess the risk of bias. Results: Amongst the 25 studies, 13 fulfilled the conditions of inclusion in this meta-analysis. The researchers further delved into the 21 miRNA expression levels from 3015 NPC patients to ascertain a link between miRNA’s predictive role and survival outcomes. The majority of the articles retrieved during this study were from China, with two studies from Canada and Malaysia. The overall pooled effect size estimation (HR) for dysregulated miRNAs was 1.590 (95% CI: 1.253–2.017), displaying that miRNA marker expression increased the risk of mortality in NPC patients by 59%. Conclusions: This meta-analysis is novel and looks at the prognostic significance of miRNAs as biomarkers in NPC patients using a continuous version pooled meta-analysis. Although our findings are ambiguous, they do show that greater miRNA expression in NPC may be associated with a lower overall survival rate. To acquire clear conclusions, more prospective studies with large cohorts are required to determine the clinical utility of miRNAs as prognostic biomarkers.