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Annals of the Academy of Medicine,... Apr 2024
Topics: Humans; Nasopharyngeal Neoplasms; Algorithms; Early Detection of Cancer; Male; Female; Middle Aged; Adult; Mass Screening; Cohort Studies; Singapore
PubMed: 38920184
DOI: 10.47102/annals-acadmedsg.2023273 -
Radiation Oncology (London, England) Jun 2024Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor-node-metastasis stages. Moreover, end-of-treatment tumor regression is...
Quantitative parameter analysis of pretreatment dual-energy computed tomography in nasopharyngeal carcinoma cervical lymph node characteristics and prediction of radiotherapy sensitivity.
BACKGROUND
Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor-node-metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck-lymph node radiotherapy in patients with NPC.
METHODS
Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression.
RESULTS
DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73-0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively.
CONCLUSION
Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool.
Topics: Humans; Male; Female; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Tomography, X-Ray Computed; Lymph Nodes; Adult; Nomograms; Aged; Lymphatic Metastasis; Neck; Retrospective Studies; Prognosis; ROC Curve; Young Adult; Radiography, Dual-Energy Scanned Projection
PubMed: 38918834
DOI: 10.1186/s13014-024-02468-9 -
BMC Oral Health Jun 2024Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and...
BACKGROUND
Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.
METHODS
A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.
RESULTS
Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267-0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036-7.825, p = 0.043).
CONCLUSIONS
We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.
Topics: Humans; Oropharyngeal Neoplasms; Male; Female; Middle Aged; Prognosis; LIM Domain Proteins; Biomarkers, Tumor; Carcinoma, Squamous Cell; Aged; Transcription Factors; Membrane Glycoproteins; Adult; Ki-67 Antigen; Hyaluronan Receptors; Tumor Suppressor Protein p53; Papillomavirus Infections; Immunohistochemistry; Aged, 80 and over; Survival Rate
PubMed: 38918827
DOI: 10.1186/s12903-024-04510-4 -
World Journal of Surgical Oncology Jun 2024Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear.
METHODS
A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators.
RESULTS
The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4 and CD8 T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86 macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters.
CONCLUSION
Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC.
Topics: Humans; Tumor Microenvironment; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Male; Survival Rate; Female
PubMed: 38918785
DOI: 10.1186/s12957-024-03441-2 -
BMC Cancer Jun 2024Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in...
Prognostic significance of platelet‑to‑albumin ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: a retrospective study of 858 cases.
BACKGROUND
Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker.
METHODS
We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation.
RESULTS
The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74).
CONCLUSIONS
In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Nasopharyngeal Carcinoma; Chemoradiotherapy; Prognosis; Nomograms; Nasopharyngeal Neoplasms; Adult; Blood Platelets; Aged; Serum Albumin; Neoplasm Staging; Young Adult; Proportional Hazards Models; Platelet Count; Biomarkers, Tumor
PubMed: 38918690
DOI: 10.1186/s12885-024-12499-w -
Asian Pacific Journal of Cancer... Jun 2024Nasopharyngeal carcinoma (NPC) is a common type of cancer in Southeast Asia. This cancer usually spreads locally and to nearby lymph nodes. One unique feature of NPC is...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a common type of cancer in Southeast Asia. This cancer usually spreads locally and to nearby lymph nodes. One unique feature of NPC is its many immune cells called tumor-infiltrating lymphocytes (TILs). Recent studies have suggested that TILs in many types of cancer can indicate a better prognosis. However, the role of TILs in NPC is still a matter of debate. Further research is necessary to determine whether TILs can be used as a prognostic factor of NPC's outcome.
METHOD
A retrospective cohort study was conducted at Sardjito Hospital to examine the records and pathological sections of patients treated for the undifferentiated subtype of NPC. Two pathologists analyzed the presence of TILs using HE-stained slides. TILs were evaluated in stromal compartments, and their association with clinicopathological variables was analyzed using the Chi-square and Fisher exact tests. The study compared overall survival in tumor patients with varying TIL levels using Kaplan-Meier survival curves and the log-rank test. A Cox regression model was used for univariate and multivariate analyses to test the significance of different factors.
RESULT
Out of the total 61 subjects, 16 (26.2%) had high stromal TILs (≥ 70%), and 45 (73.8%) had low stromal TILs (<70%). The subjects' sex, age, and tumor stage did not affect the OS. However, high stromal TILs (≥ 70%) showed a significant association with a longer OS (log-rank test p = 0.006, HR 0.37, 95% CI 0.17-0.79, log-rank p = 0.006). Moreover, multivariate analysis confirmed that TILs were an independent prognostic indicator for OS (aHR 0.015).
CONCLUSION
TILs correlate positively with overall survival in the undifferentiated NPC subtype and are an independent prognostic indicator.
Topics: Humans; Lymphocytes, Tumor-Infiltrating; Male; Female; Prognosis; Retrospective Studies; Nasopharyngeal Neoplasms; Middle Aged; Nasopharyngeal Carcinoma; Survival Rate; Adult; Carcinoma; Follow-Up Studies; Aged; Neoplasm Staging
PubMed: 38918661
DOI: 10.31557/APJCP.2024.25.6.1997 -
PeerJ 2024This study aims to explore the prognostic values of routine pre-treatment hematological parameters in patients with nasopharyngeal carcinoma (NPC).
PURPOSE
This study aims to explore the prognostic values of routine pre-treatment hematological parameters in patients with nasopharyngeal carcinoma (NPC).
METHODS
The hematological parameters and clinical data of patients with NPC were collected from January 2012 to December 2013 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The survival statistics were obtained by regularly following-up the patients. The cut-off values for the hematological parameters were calculated using X-tile software. SPSS version 24.0 was used for the statistical analysis. The relationship between the hematological parameters and the prognosis of patients with NPC was analyzed using the Kaplan-Meier method and Cox multivariate regression. The discriminating abilities of the factors, which predict the prognosis, were evaluated by utilizing the receiver operating characteristic (ROC) area under the curve (AUC).
RESULTS
This study included 179 patients with NPC. Multivariate analysis shows that pretreatment platelet-to-lymphocyte ratio (PLR; hazard ratio; HR = 0.44, 95% CI [0.21-0.91], = 0.029), serum albumin (ALB; HR = 2.49, 95% CI [1.17-5.30], = 0.018), and globulin (GLO; HR = 0.44, 95% CI [0.21-0.90], = 0.024) are independent predictors for 5-year overall survival (OS) in patients with NPC. In addition, pre-treatment PLR (HR = 0.47, 95% CI [0.25-0.90], = 0.022) and pre-treatment GLO (HR = 0.37, 95% CI [0.19-0.72], = 0.001) are associated with 5-year progression-free survival (PFS) in patients with NPC. Based on the results of the multivariate analysis, we proposed a new biomarker GLO-PLR, which is observably correlated with the T stage, N stage and clinical stage in patients with NPC. The OS resolving ability of the GLO-PLR evaluated by AUC is 0.714, which is better than those of GLO and PLR. The PFS resolving ability of the GLO-PLR evaluated by AUC was 0.696, which is also better than those of GLO and PLR.
CONCLUSION
Pre-treatment PLR, ALB, and GLO are independent predictors of 5-year OS in patients with NPC, where PLR and GLO are also independent predictors of 5-year FPS. Compared with other hematological parameters, the proposed GLO-PLR is an inexpensive, effective, objective, and easy-to-measure marker for predicting the prognosis of NPC.
Topics: Humans; Male; Female; Middle Aged; Nasopharyngeal Carcinoma; Retrospective Studies; Nasopharyngeal Neoplasms; Prognosis; Adult; Aged; Serum Albumin; Platelet Count; ROC Curve; Kaplan-Meier Estimate; Lymphocyte Count; Blood Platelets
PubMed: 38915379
DOI: 10.7717/peerj.17573 -
BMC Cancer Jun 2024Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We...
BACKGROUND
Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer.
PATIENTS AND METHODS
We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period.
RESULTS
We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers.
CONCLUSIONS
Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.
Topics: Humans; Male; Female; Laryngeal Neoplasms; Middle Aged; Oropharyngeal Neoplasms; Aged; Surveys and Questionnaires; Prospective Studies; Depression; Mouth Neoplasms; Adult; Quality of Life; Finland; Social Class; Neoplasm Staging; Socioeconomic Factors; Time-to-Treatment
PubMed: 38914952
DOI: 10.1186/s12885-024-12517-x -
Frontiers in Immunology 2024To investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma...
PURPOSE
To investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma (LANPC).
METHODS
Patients with stage III-IVA NPC who received IC or IC + PD-1 inhibitor were included. The chi-square test and multivariate logistic regression analysis were used for statistical analysis.
RESULTS
A total of 225 patients were identified, including 193 (85.8%) and 32 (14.2%) who received IC alone and IC + PD-1 inhibitor, respectively. The addition of PD-1 inhibitor to IC significantly improved the tumor response than those treated with IC alone. The complete response (CR), partial response, stable disease, and progressive disease rates of 4.7% vs. 31.3%, 69.4% vs. 62.5%, 24.9% vs. 6.3%, and 1.0% vs. 0% in patients receiving IC alone and IC + PD-1 inhibitor, respectively (P<0.001). The results of the multivariate logistic regression showed that receiving PD-1 inhibitor was an independent predictor influencing the CR rate of patients (odds ratio 9.814, P<0.001). The most common toxicity by using IC and PD-1 inhibitor was hematological toxicity. In terms of non-hematological toxicity, 7 (21.9%) patients experienced thyroid dysfunction and all of them were hyperthyroidism. No grade 5 toxicities were found. In those who received IC and PD-1 inhibitor, the one-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 100%, 96.9%, 96.9%, and 100%, respectively.
CONCLUSION
The addition of PD-1 inhibitor to IC has promise as an effective treatment approach for LANPC. More studies are expected to provide further insights into the optimal use of this treatment strategy, paving the way for more personalized and effective treatment options for patients with LANPC.
Topics: Humans; Male; Female; Nasopharyngeal Carcinoma; Middle Aged; Induction Chemotherapy; Adult; Nasopharyngeal Neoplasms; Aged; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Programmed Cell Death 1 Receptor; Treatment Outcome; Neoplasm Staging; Young Adult; Retrospective Studies
PubMed: 38911859
DOI: 10.3389/fimmu.2024.1415246 -
Nature Communications Jun 2024Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in...
Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.
Topics: Humans; Docetaxel; Drug Resistance, Neoplasm; Nasopharyngeal Carcinoma; Cell Line, Tumor; Nasopharyngeal Neoplasms; Pyroptosis; Ubiquitination; Animals; Ubiquitin-Protein Ligases; Mice; Mice, Nude; Female; Dynamins; Reactive Oxygen Species; Phosphoprotein Phosphatases; Male; Xenograft Model Antitumor Assays; Mice, Inbred BALB C; Antineoplastic Agents; Phosphorylation; Mitochondrial Proteins; Fluorouracil; Gene Expression Regulation, Neoplastic; Mitochondria; Cisplatin; Middle Aged; Gasdermins
PubMed: 38906860
DOI: 10.1038/s41467-024-49675-2