Nicotine-induced activation of cholinergic receptor nicotinic alpha 5 subunit mediates the malignant behaviours of laryngeal squamous epithelial cells by interacting with RABL6.

Nicotine, a crucial constituent of tobacco smoke, can bind to and activate nicotinic acetylcholine receptors (nAChRs), thereby regulating various biological functions. However, the specific mechanisms through which nicotine mediates nAChRs to regulate the metastasis of laryngeal squamous cell carcinoma (LSCC) remain elusive. In this study, smoking status was found to be closely associated with metastasis in patients with LSCC. In addition, nicotine exposure potentiated the hematogenous and lymphatic metastatic capacity of LSCC cells. Nicotine activates membrane-bound CHRNA5, promoting cell migration and invasion, EMT and cell-ECM adhesion in LSCC. Furthermore, this study demonstrated that the Ras superfamily protein RABL6 directly interacted with CHRNA5, which preferentially binds to the RABL6-39-279aa region, and this interaction was enhanced by nicotine. Nicotine-mediated activation of CHRNA5 enhanced its interaction with RABL6, triggering the JAK2/STAT3 signalling pathway and eventually augmenting the metastatic potential of LSCC cells. This study reveals a novel mechanism through which nicotine-mediated CHRNA5-RABL6 interaction promotes the metastasis of LSCC. The findings of this study may help to develop effective strategies for improving the outcome of patients with LSCC in clinical settings.

Camrelizumab-based induction chemoimmunotherapy in locally advanced stage hypopharyngeal carcinoma: phase II clinical trial.

This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

Erratum: [Corrigendum] Survival outcomes in patients with T3­4aN0M0 glottic laryngeal squamous cell carcinoma and evaluation of postoperative radiotherapy.

[This corrects the article DOI: 10.3892/ol.2022.13554.].

Integrative methylome and transcriptome analysis reveals epigenetic regulation of Fusobacterium nucleatum in laryngeal cancer.

The aetiological mechanisms of Fusobacterium nucleatum in laryngeal cancer remain unclear. This study aimed to reveal the epigenetic signature induced by F. nucleatum in laryngeal squamous cell carcinoma (LSCC). Combined analysis of methylome and transcriptome data was performed to address the functional role of F. nucleatum in laryngeal cancer. Twenty-nine differentially expressed methylation-driven genes were identified by mapping the methylation levels of significant differential methylation sites to the expression levels of related genes. The combined analysis revealed that F. nucleatum promoted Janus kinase 3 (JAK3) gene expression in LSCC. Further validation found decreased methylation and elevated expression of JAK3 in the F. nucleatum-treated LSCC cell group; F. nucleatum abundance and JAK3 gene expression had a positive correlation in tumour tissues. This analysis provides a novel understanding of the impact of F. nucleatum in the methylome and transcriptome of laryngeal cancer. Identification of these epigenetic regulatory mechanisms opens up new avenues for mechanistic studies to explore novel therapeutic strategies.

Fusobacterium nucleatum facilitates proliferation and autophagy by activating miR-361-3p/NUDT1 axis through oxidative stress in hypopharyngeal squamous cell carcinoma.

BACKGROUND: To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: The prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins. RESULTS: Fn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH-, which could be proven by H2O2 assay and N-acetylcysteine. CONCLUSIONS: Higher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.

Tetraspanin CD63 reduces the progression and metastasis of head and neck squamous cell carcinoma via KRT1-mediated cell cycle arrest.

Despite the fact that metastasis is the leading cause of death in patients with head and neck squamous cell carcinoma, fundamental questions about the mechanisms that enable or inhibit metastasis remain unanswered. Tetraspanin CD63 has been linked to tumor progression and metastasis. However, few studies have examined the role of CD63 in HNSCC. In this study, we discovered that CD63 levels were abnormally altered in HNSCC tissue compared to adjacent tissue (n = 69 pairs), and that this was linked to prognosis. Through functional in vitro and in vivo experiments, the roles of CD63 in HNSCC were confirmed. Overexpression of CD63 inhibited the progression and metastasis of HNSCC cells. Using mass spectrometry and co-immunoprecipitation assays, we discovered that KRT1 could be a direct interacting partner of CD63. Furthermore, both CD63 and KRT1 expression was significantly decreased in metastatic tissue compared with primary tumor tissue (n = 13 pairs), suggesting that CD63 and KRT1 play a role in reducing the metastasis of HNSCC. In summary, we reveal a previously unrecognized role of CD63 in regulating KRT1-mediated cell cycle arrest in HNSCC cells, and our findings contribute to defining an important mechanism of HNSCC progression and metastasis.

Fusobacterium nucleatum-triggered purine metabolic reprogramming drives tumorigenesis in head and neck carcinoma.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a vital pro-oncogenic bacterium. Our previous study revealed that a high abundance of F. nucleatum in head and neck squamous cell carcinoma (HNSCC) is correlated with poor patient prognosis. However, the impact of F. nucleatum on metabolic reprogramming and tumor progression in HNSCC awaits more exploration. METHODS: Liquid chromatography‒mass spectrometry (LC‒MS) was applied to analyze the altered metabolites in a head and neck carcinoma cell line (AMC-HN-8) after coculture with F. nucleatum for 24 hrs and 48 hrs. Both univariate and multivariate analyses were used to screen for differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment analysis was further used to explore the metabolic changes. RESULTS: We observed a significantly altered metabolic profile in AMC-HN-8 cells over time after coculture with F. nucleatum. Among the several enriched pathways, the purine metabolic pathway was the most significantly enriched (P = 0.0005), with downregulation of purine degradation. Furthermore, uric acid, the end product of purine metabolism, significantly reversed F. nucleatum-triggered tumor progression and altered the intracellular reactive oxygen species (ROS) level. Moreover, the negative correlation between the serum uric acid level and the abundance of F. nucleatum was verified in 113 HNSCC patients (P = 0.0412, R = - 0.1924). CONCLUSIONS: Our study revealed obviously aberrant purine metabolism driven by F. nucleatum in HNSCC, which was closely related to tumor progression and patient prognosis. These findings indicate the possibility of targeting F. nucleatum-induced purine metabolism reprogramming in the future treatment of HNSCC.

A Survival Nomogram Containing Lymph Node Ratio for Hypopharyngeal Carcinoma Patients After Neck Dissection.

OBJECTIVE: The purpose of our study is to establish a survival nomogram based on lymph node ratio (LNR) in hypopharyngeal carcinoma. STUDY DESIGN: Retrospective cohort study. SETTING: Hypopharyngeal squamous cell carcinoma (HPSCC) is prone to regional metastasis. Emerging evidence has shown that LNR is a promising prognostic factor in HPSCC. METHODS: From January 2004 to January 2018, 411 HPSCC patients who underwent neck dissection at our institution were retrospectively studied. The enrolled patients were divided into training and validation cohorts at a ratio of 7:3. A survival nomogram was finally built based on factors screened from multivariate analysis using the bidirectional stepwise method. RESULTS: LNR was superior to other nodal classifications for survival prediction and was used to establish the R classification. A nomogram was developed using R classification (p < .001), pT classification (p < .001), tumor invasive depth (p < .001), and internal jugular vein adhesion (p = .001). The C-indexes were 0.712 and 0.703 in the training and validation dataset. The 36- and 60-month AUCs were 0.767 and 0.766 in the training dataset and 0.713 and 0.757 in the validation dataset, respectively. The calibration curves showed relatively good agreement between the predicted and actual probability. CONCLUSION: Based on the LNR, we developed a survival nomogram for HPSCC after neck dissection, which will be a practical tool to discriminate patients with different survival risks.

Predictive value of pathological carcinoma size in patients with T2 glottic laryngeal squamous cell carcinoma.

BACKGROUND: T2N0M0 glottic laryngeal squamous cell carcinoma (LSCC) is a common type of laryngeal cancer. OBJECTIVES: The objective of this research was to assess the predictive value of tumor size for the rates of overall survival (OS) and disease-free survival (DFS) as determined by postoperative pathological examination in patients with T2 LSCC. METHODS: A retrospective study was conducted on 535 successive patients with T2 glottic LSCC who underwent operation from 2005 to 2010. The effect of tumor size on OS and DFS results was evaluated by the affected area. RESULTS: Of the cohort, 528 (98.7%) were male, and 7 (1.3%) were female, with an average age of 60.1 ± 9.4 years. The 10-year DFS and OS rates were 72.1% and 76.3%, respectively. The tumor diameter and area cut-off values that best discriminated OS and DFS rates were 1.35 cm and 1 cm2, respectively. Patients with glottis carcinoma with a longer tumor diameter and larger tumor area had inferior OS and DFS rates. Tumor diameter and tumor area were independent predictive factors for the rates of OS and DFS in patients with T2 glottic LSCC. CONCLUSION AND SIGNIFICANCE: This research showed that patients with T2 glottic LSCC with a carcinoma diameter >1.35 cm or a tumor area >1 cm2 have worse survival outcomes. These factors independently predict survival outcomes in patients.

A Nomogram to Predict Nodal Response after Induction Chemotherapy for Hypopharyngeal Carcinoma.

BACKGROUND: For hypopharyngeal carcinoma, metastatic neck nodes with a low response to induction chemotherapy (ICT) should not be managed with concomitant chemoradiotherapy (CCRT), and the prediction of chemosensitivity before ICT could prevent adverse events from occurring during chemotherapy. In this study, we developed a nomogram to predict the regional response to ICT. METHODS: A total of 153 hypopharyngeal carcinoma patients with regional metastasis treated with ICT in our institution from January 2010 to September 2020 were retrospectively studied. According to ICT response evaluated by RECIST 1.1, patients were divided into chemo-insensitive (PR < 70%/SD/PD) (group 1) and chemosensitive (CR/PR ≥ 70%) (group 2) groups. Patients' clinical, image, and hematologic data before ICT were collected. The nomogram was built based on multivariate analysis and stepwise logistic regression and was evaluated from the aspects of discrimination and calibration. RESULTS: A nomogram based on five critical predictors, namely, tumor differentiation degree, T classification, metastatic lymph node size, number of lymph node metastases, and cervical nodal necrosis, was developed. The areas under the curve (AUC) values were 0.76 and 0.70 after adjusting the results using bootstrap methods. The calibration curve showed relatively good agreement between the predicted and observed probabilities. CONCLUSIONS: Our nomogram yielded good accuracy in predicting the regional ICT response and will be a useful tool to assist clinicians in decision making. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:849-855, 2023.

Tumour microbiota structure predicts hypopharyngeal carcinoma recurrence and metastasis.

Objectives: The relationship between microbiota and HPSCC recurrence and metastasis remains uncertain. This study aimed to investigate the role of the tumour microbiota in the disease-free survival (DFS) of HPSCC patients. Materials and methods: Formalin-fixed paraffin-embedded (FFPE) tumour tissues were collected from 103 patients with HPSCC for 16S rRNA sequencing. We analysed the tumour microbiota in HPSCC patients with recurrence/metastasis and nonrecurrence/metastasis. The linear predictor score (LPS) was calculated based on the Cox regression model to assess the risk of recurrence and metastasis. Then, a time-dependent ROC curve was used to evaluate the prognostic power of the LPS. Results: The phyla Bacteroidota, Firmicutes and Proteobacteria were the most abundant bacterial taxa in the tumour tissues. Eubacterium_coprostanoligenes_group (hazard ratio [HR] = 0.289, 95% confidence interval [CI] 0.137-0.608, p= 0.001) and Prevotella (HR = 3.744, 95% CI 1.439-9.738, p= 0.007) were independent predictors of DFS. The predicting classifier for recurrence and metastasis risk yielded an area under the curve (AUC) of 0.838 at 3 years and 0.860 at 5 years. Conclusion: Our study demonstrated the relationship between tumour microbiota and recurrence and metastasis in patients with HPSCC.

Epidemiological, Clinical, and Oncological Outcomes of non-Alcohol Drinking and non-Smoking Laryngeal Squamous Cell Carcinoma Patients: A Distinct Entity.

Purpose: To explore the discrepancy in clinicopathological and prognostic features between smoking and alcohol drinking (SA) and non-smoking and non-alcohol drinking (NSNA) patients with laryngeal squamous cell carcinoma (LSCC). Methods: This retrospective study including 1735 patients with LSCC was conducted from January 2005 to December 2010, which were categorized into 4 groups, NSNA group, smoking only group, alcohol-drinking only group, and SA group. We compared overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method and indicated clinicopathological features by Cox proportional hazards regression models before and after propensity score matching (PSM). Results: A total of 415 patients (23.92%) were identified as NSNA. The SA group was predominantly patients ≤60 years old (46.63%) while the NSNA group was more older (58.07%). NSNA group was more likely to present at earlier disease stage and more female. No significant difference in OS (P = .685) and DFS (P = .976) was found between the 2 groups. In addition to age and recurrence and metastasis being common independent prognostic factors in terms of OS in both groups of patients, NSNA group also exhibited other factors, namely tumor area >3.7 cm2 and positive resection margin. For DFS, N + stage, tumor size >3.7 cm2, and positive resection margin were prognostic features specific to NSNA group. Conclusion: The outcome is similar in LSCC patients with and without SA. NSNA group shows a distinct profile from that found in SA group. Clinicopathological features from NSNA group should be considered for LSCC management.

Survival outcomes in patients with T3-4aN0M0 glottic laryngeal squamous cell carcinoma and evaluation of postoperative radiotherapy.

This study aimed to evaluate the clinical outcomes of patients with T3-4aN0M0 glottic laryngeal squamous cell carcinoma (LSCC) treated with laryngectomy, and to assess the postoperative radiotherapy (PORT) results in terms of the survival of T3-T4aN0M0 patients with negative margins. This was a retrospective review of 369 T3-4aN0M0 glottic LSCC cases. The 5-year cancer-specific survival (CSS) and overall survival (OS) rates were 67.5 and 66.7%, respectively. Patients who received total laryngectomy had worse survival [5-year CSS, 62.5%; disease-free survival (DFS), 56.2%] than those who underwent partial laryngectomy (5-year CSS, 79.3%; DFS, 65.4%). More advanced-stage cancer is a predictor of poor survival. There was no significant difference in CSS or DFS between patients with positive margins following rescue therapy and those with negative margins. Furthermore, no difference in the survival rates was observed between patients with negative margins who received PORT and those who did not (5-year DFS: 59.1 vs. 63.8%, P=0.057 and CSS: 62.5 vs. 69.5%, P=0.074). For T3-4aN0M0 glottic LSCC patients, surgical treatment remained a good option, as it can achieve satisfactory oncological outcomes. However, PORT did not increase survival in surgically managed pT3-4aN0M0 LSCC patients with negative margins.

Oncologic outcomes of transoral laser microsurgery versus open partial laryngectomies in the management of early stage glottic carcinoma.

BACKGROUND: The oncologic outcomes between transoral laser microsurgery (TLM) and open partial laryngectomy (OPL) using comprehensive analysis in one clinical center is rare. The purpose of this study was to evaluate the oncologic outcomes of TLM in patients with early stage glottic carcinoma, and to compare the results with OPL. SUBJECTS AND METHODS: Records of 425 glottic carcinoma patients with T1 - T2 stage treated with TLM, vertical partial laryngectomy (VPL), and cricohyoidoepiglottopexy (CHEP) from 2005 to 2010 were retrospectively analyzed. The overall survival (OS), disease-specific survival (DSS), and laryngeal function preservation (LFP) of these three treatments were assessed. RESULTS: One hundred and twenty-two patients were treated with TLM. Regarding OPL, 167 patients underwent VPL, and 136 patients underwent CHEP. The mean age was 59.7 years, with men accounting for 97.2 % of all cases. The OS, DSS, and LFP rates of patients with anterior commissure (AC) involvement undergoing TLM were worse than those of patients without AC involvement, but these differences were not statistically significant. The 5-year OS, DSS, and LFP of patients undergoing TLM were 88.4 %, 89.9 %, and 83.5 %, respectively, and the oncologic outcomes of patients undergoing TLM, VPL, and CHEP were not statistically different. CONCLUSION: Glottic carcinoma patients with early stage treated with TLM experience satisfactory oncologic outcomes. No compelling difference in oncologic outcomes among three treatments of TLM, VPL and CHEP, as well as VPL and CHEP can be alternatives to patients who are not suitable for receiving TLM.

The management of metastatic neck nodes following induction chemotherapy in N2/3 classification hypopharyngeal carcinoma.

BACKGROUND: For patients with less chemosensitive neck nodes, poor prognosis after chemoradiotherapy (CRT) could be predicted and neck dissection is needed. METHODS: Ninety-two N2/3 hypopharyngeal carcinoma patients were retrospectively studied. According to response after induction chemotherapy (ICT), patients were treated with neck dissection followed by concurrent CRT (CCRT) (group 1), surgery plus postoperative CRT (group 2), or CCRT for primary and regional sites (group 3). RESULTS: Overall survival and disease-free survival rates of group 1 were significantly higher than group 2 (p = 0.038, p = 0.031) and group 3 (both p = 0.018). Regional control rate of group 1 was significantly higher than group 3 (p = 0.041). There were no significant differences between groups 1 and 2 regarding local and regional control (p = 0.746, p = 0.302). CONCLUSIONS: Neck dissection followed by CCRT is the best choice for patients with responsive primary but nonresponsive nodes.

Fusobacterium nucleatum impairs DNA mismatch repair and stability in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Dysbiosis of the laryngeal microbiota has been demonstrated to the development of head and neck squamous cell carcinoma (HNSCC), but the association of Fusobacterium and Fusobacterium nucleatum (F. nucleatum) with DNA mismatch repair (MMR) and microsatellite instability (MSI) has not been investigated. METHODS: The abundance of Fusobacterium and F. nucleatum, the status of deficient MMR (dMMR) and MSI, and MMR-related gene expression were analyzed in 171 HNSCC tissues, 61 paired para-tumor tissues, and 60 vocal cord polyp tissues. The molecular mechanism of F. nucleatum and MMR-related gene expression were investigated in two human HNSCC cell lines (Tu 686 and FD-LSC-1). RESULTS: Our results demonstrated that a high Fusobacterium abundance was detected in the HNSCC tissues and was exaggerated in the recurrent patients. We further found that a high Fusobacterium abundance was detected in the HNSCC tissues with dMMR and MSI. The Fusobacterium abundance was negatively correlated with the expression of MLH1, MSH2, and MSH6 in the HNSCC tissues. The Fusobacterium abundance was closely associated with the F. nucleatum abundance in the HNSCC tissues. F. nucleatum increased miR-205-5p expression to suppress MLH1, MSH2, and MSH6 expression via the TLR4- and MYD88-dependent innate immune signaling pathway, resulting in dMMR, DNA damage, and cell proliferation in HNSCC. CONCLUSIONS: F. nucleatum impacts HNSCC epigenetic changes in tissues with dMMR to promote DNA damage and cell proliferation by suppressing MMR-related gene expression via the TLR4/MYD88/miR-205-5p signaling pathway, which is valuable in the development of efficient strategies for HNSCC prevention and treatment. LAY SUMMARY: This study clearly indicates that Fusobacterium induced head and neck squamous cell carcinoma (HNSCC) aggressiveness to affect poor prognosis in HNSCC patients by epigenetic alteration of DNA mismatch repair (MMR) and microsatellite instability. Moreover, the research has shown that Fusobacterium nucleatum ( F. nucleatum ) impacts HNSCC epigenetic changes in tissues with deficient MMR to promote DNA damage and cell proliferation by suppressing MMRrelated gene expression via the TLR4/MYD88/miR-205-5p signaling pathway.

The Prognostic Capacity of Systemic Inflammation Response Index, Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio, and Platelet-to-Lymphocyte Ratio in Patients with Hypopharyngeal Squamous Cell Carcinoma.

INTRODUCTION: Systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been proposed as peripheral blood biomarkers. We compared these blood biomarkers to identify the best predictor in patients with hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: We conducted a retrospective study on 304 patients with HPSCC. SIRI was divided into three groups using X-tile version 3.6.1. The optimal cut-off points for NLR, LMR, and PLR were selected through RStudio. We compared the prognostic capacity of SIRI with that of NLR, LMR, and PLR using receiver operating characteristic curves. RESULTS: Smoking, cancer in the postcricoid region, lymph node metastasis (N+), extracapsular invasion, SIRI in the highest tertile (>2.80), and LMR in the lowest tertile (<5.0) may cause poor 5-year overall survival (OS) in patients with HPSCC. Local and distant recurrences may occur earlier in those with lymph node metastasis and a tumor invading beyond the mucosa layer. CONCLUSIONS: SIRI was a better predictor of OS than LMR, PLR, and NLR in HPSCC patients. SIRI in the highest tertile (>2.80) and LMR in the lowest tertile (<5.0) may cause poor 5-year OS.

Cross-comparison of microbiota in the oropharynx, hypopharyngeal squamous cell carcinoma and their adjacent tissues through quantitative microbiome profiling.

Aims: To clarify the absolute abundance of microbial communities on hypopharyngeal squamous cell carcinoma and their correlation to those in the oropharynx. Methods: Clinical data, swabs, and tissue samples from 27 HPSCC patients were collected in this study and divided into three sampling groups: 19 oropharyngeal mucosa (OPM), 27 hypopharyngeal carcinomas tissues (HC), and 26 corresponding adjacent tissues (AT). Relative microbiome profiling (RMP), and quantitative microbiome profiling (QMP) of 16S rRNA amplicon sequencing were used for analysis. Results: Beta-diversity showed that abundance and phylogenetic tree in OPM group were less when compared to either HC and AT. Although HC and AT were found to have similar microbiota, Bray-Curtis based beta-diversity still highlighted differences. Fusobacterium, Porphyromonas, Haemophilus, and Peptostreptococcus at the genus level in OPM were positively correlated with HC. After categorizing HC through TNM staging, the abundance of genera Fusobacterium, Parvimonas, and Dialister were found to be enhanced in higher T classifications (T3-4) and advanced stages (Ⅳ). Conclusions: QMP yielded more comprehensive results than RMP. Dysbiosis was found in OPM groups and could be used to narrow down differential microbiome for the HC group. Genera of Parvimonas, Fusobacterium, and Dialister were deemed asrisk factors of advanced HPSCC.

Preoperative tracheotomy in the treatment of upper airway obstruction of patients with advanced stage supraglottic carcinoma.

BACKGROUND: Preoperative tracheotomy is an effective option that secures upper airway patency in laryngeal carcinoma patients suffering from upper airway obstruction, but the influence of this treatment on oncologic outcomes of laryngeal carcinoma remains controversial. The purpose of this study was to determine the impact of preoperative tracheotomy on overall survival in supraglottic carcinoma patients with tumor obstruction of the upper airway, and explore the potential causes. MATERIALS AND METHODS: This retrospective study collected 243 consecutive patients with advanced stage supraglottic carcinoma from 2005 to 2010. Preoperative tracheotomy in the management of upper airway obstruction in patients with supraglottic carcinoma was analyzed. RESULTS: The mean age was 60.9 years at diagnosis, with men accounting for 98.4% of all patients. Thirty nine (16.0%) patients presenting with tumor obstruction of the upper airway required preoperative tracheotomy. T4 stage patients had higher rate of tracheotomy than those of patients with T3 stage (36.8% vs 12.2%). Patients with upper airway obstruction presented with greater tumor area compared with patients without (13.7 cm2 vs 9.0 cm2). The optimal cutoff value of tumor area for tracheotomy and OS rate were both at 10 cm2. Supraglottic patients with upper airway obstruction receiving preoperative tracheotomy had poorer OS rate compared with patients without. T stage and tumor area were correlated with upper airway obstruction, and these two variables were independent predictors of OS rate in supraglottic carcinoma patients. CONCLUSIONS: Advanced stage supraglottic carcinoma patients with upper airway obstruction undergoing preoperative tracheotomy experienced worse overall survival. Advanced T stage and greater tumor size were associated with upper airway obstruction, indicating that the negative influence of tumor obstruction on survival may be cause by these two preoperative variables. Therefore, preoperative tracheotomy acts only as an alternative procedure, and is not a prognostic agent.

A positive feed-forward loop between Fusobacterium nucleatum and ethanol metabolism reprogramming drives laryngeal cancer progression and metastasis.

Alcohol consumption, which affects the structure and composition of the laryngeal microbiota, is one of the most important risk factors for laryngeal squamous cell cancer (LSCC). Our results demonstrated that high enrichment of Fusobacterium nucleatum (F. nucleatum) in LSCC was associated with poor prognosis. F. nucleatum increased miR-155-5p and miR-205-5p expression to suppress alcohol dehydrogenase 1B (ADH1B) and transforming growth factor ß receptor 2 (TGFBR2) expression by activating innate immune signaling, resulting in ethanol metabolism reprogramming to allow F. nucleatum accumulation and PI3K/AKT signaling pathway activation to promote epithelial-mesenchymal transition, further exacerbating the uncontrolled progression and metastasis of LSCC. Therefore, the positive feed-forward loop between F. nucleatum and ethanol metabolism reprogramming promotes cell proliferation, migration, and invasion to affect LSCC patient prognosis. The amount of F. nucleatum is a potential prognostic biomarker, which yields valuable insight into clinical management that may improve the oncologic outcome of patients with LSCC.