Laryngeal Squamous Cell Cancer Research Articles

A case series of interventions and outcomes in patients with laryngeal squamous cell cancer.

A case series of interventions and outcomes in patients with laryngeal squamous cell cancer.

MiR-125 family improves the radiosensitivity of head and neck squamous cell carcinoma

BackgroundMiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC).MethodsFirst, we systematically analyzed the role of the miR-125 family in HNSCC using the TCGA database and found that miR-125a-5p is associated with radiotherapy. We then performed comprehensive enrichment analysis of miR-125a-5p and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin.ResultsMiR-125 family members exhibited significantly different expression in HNSCC. They were significantly associated with tumor–node–metastasis staging, clinical stages, and histological grades. Radiation therapy had a statistically effect on miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. The proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to the other groups. The radiation effect was enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes.ConclusionsMiR-125 family members could be prognostic biomarkers of HNSCC and improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on LSCC.

Incidental thyroid carcinomas: experiences related to the surgery of head and neck cancers.

Incidental thyroid carcinomas (ITCs) in patients undergoing head and neck surgery are rare, but there are no standard guidelines for the treatment of this situation. This retrospective study sought to detail our experiences in the treatment of ITCs related to the surgery of head and neck cancers. We conducted a retrospective analysis of the data about the ITCs in the patients with head and neck cancer, who underwent surgical treatments at Beijing Tongren Hospital in the past 5 years. The number and size of the thyroid nodules, postoperative pathology, follow-up results, and other information were recorded in detail. All the patients underwent surgical treatment and were followed-up for >1 year. A total of 11 patients (10 male and 1 female) with ITC were included in this study. The patients had an average age of 58 years. Most of the patients (72.7%, 8/11) had laryngeal squamous cell cancer, and 7 were diagnosed with thyroid nodules on ultrasound. The surgical procedures for laryngeal and hypopharyngeal cancers included partial laryngectomy, total laryngectomy, and hypopharyngectomy. All the patients underwent thyroid stimulating hormone (TSH) suppression therapy. No recurrence or mortality events from thyroid carcinoma were observed. More attention needs to be paid to ITCs in head and neck surgery patients. Additionally, more research and the long-time follow-up of ITC patients are needed to extend understandings. For patients with head and neck cancers, if the suspicious thyroid nodules are found pre-operatively by ultrasound, fine-needle aspiration (FNA) is recommended. If FNA cannot be performed, the guidelines for thyroid nodules should be followed. In patients with postoperative ITC, TSH suppression therapy and follow-up is indicated.

Knockout of the histone methyltransferase NSD1 leads to a decrease in cell proliferation and an increase in sensitivity to cisplatin in laryngeal squamous cell carcinoma

Introduction. The histone methylation regulates gene expression and plays a role in genomic stability participating in DNA repair. Dimethylation of histone 3 lysine 36 (H3K36me2) is an important histone modification which is responsible for gene expression activation. H3K36me2 is a product of methyltransferase activity of NSD1, NSD2, NSD3, and ASH1L proteins. NSD1 mutations are known to often occur in head and neck squamous carcinoma. The presence of NSD1 mutations highly correlates with increased survival, especially for patients with laryngeal cancer. The aim of this study was an in vitro investigation of the role of NSD1 in the cell proliferation of laryngeal squamous cell cancer and non-small lung cancer cells, as well as a study of the effect of disruption of the NSD1 gene expression on cisplatin treatment response.Material and Methods. Using TCGA, correlation analysis was performed to compare NSD1 wild type and mutant patient survival. NSD1 knockout cell lines models of laryngeal and non-small cell lung cancer were developed using the CRISPR/ Cas9 system. The effect of NSD1 knockout on H3K36me2 level was evaluated by western blot. Proliferation and IC50 of cisplatin in control and knockout cells were studied as well.Results. It was demonstrated that NSD1 knockout decreased the H3K36me2 level and cell proliferation in laryngeal squamous cell cancer cells and increased the sensitivity of head and neck cancer cells to cisplatin treatment, while there was no effect of NSD1 knockout in a non-small cell lung cancer cell line.Conclusion. Based on the data obtained, it can be concluded that the NSD1 protein is a potential target for inhibitor development following in vitro and in vivo testing in head-neck squamous cell carcinoma models. More studies are needed for better understanding of the regulation of tumor cell growth by NSD1.

Tumor Volume Staging Provides a Comparable Stratifying for Laryngeal Squamous Cell Cancer According to T Stages.

The prognostic significance of tumor volume (TV) in laryngeal squamous cell cancer (LSCC) has been demonstrated previously. Still, its clinical use is uncertain, and a method for accurate staging for TV is lacking. This study aimed to develop an objective staging and determine the effect of tumor volume on disease outcome after surgical treatment for LSCC. This study was designed retrospectively. Patients with LSCC who underwent laryngectomy were identified. Discretization for optimal scaling level of Tumor Volume (TV) was performed by Catreg Version 3.0. The rate of cancer recurrence, disease-free survival (DFS), and overall survival (OS) rate were calculated and compared between T stage and TV staging. Kaplan-Meier survival analysis was performed for comparison. 206 LSCC patients enrolled in the study. TV was found significantly higher in patients with cartilage invasion, contralateral nodal metastasis, and extranodal extension (p = 0.004, 0.010, and 0.021, respectively). TV and lymph node density LND showed a low significant positive correlation (p = 0.015, r = 0.169). TV was 7.25 + 7.53ml on average, and TV above the mean value was found to be an independent risk factor for OS and DFS (p = 0.043, HR = 1.8; CI95% for HR: 1.02-3.44 and p < 0.001, HR = 3.7; CI95% for HR: 1.8-7.3, respectively). The optimal scaling level of TV was found in three-level; group 1: TV ≤ 7.07, group 2: 7.07 < TV ≤ 14.09, and group 3: TV ≥ 14.10. This categorization of TV has obtained significant discretization between patients for DFS and OS (Long-Rank = 0.038 and < 0.001). This classification may provide better performance in addition to helping the T stage in determining prognosis, especially in patients with advanced laryngeal SCC.

Cell Cycle-Related Gene SPC24: A Novel Potential Diagnostic and Prognostic Biomarker for Laryngeal Squamous Cell Cancer.

Laryngeal squamous cell cancer (LSCC) is a common malignant tumor with a high degree of malignancy, and its etiology remains unclear. Therefore, screening potential biomarkers is necessary to facilitate the treatment and diagnosis of LSCC. Robust rank aggregation (RRA) analysis was used to integrate two gene expression datasets of LSCC patients from the Gene Expression Omnibus (GEO) database and identify differentially expressed genes (DEGs) between LSCC and nonneoplastic tissues. A gene coexpression network was constructed using weighted gene correlation network analysis (WGCNA) to explore potential associations between the module genes and clinical features of LSCC. Combining differential gene expression analysis and survival analysis, we screened potential hub genes, including CDK1, SPC24, HOXB7, and SELENBP1. Subsequently, western blotting and immunohistochemistry were used to test the protein levels in clinical specimens to verify our findings. Finally, four candidate diagnostic and prognostic biomarkers (CDK1, SPC24, HOXB7, and SELENBP1) were identified. We propose, for the first time, that SPC24 is a gene that may associate with LSCC malignancy and is a novel therapeutic target. These findings may provide important mechanistic insight of LSCC.

Diagnostic and Prognostic Value of microRNAs in Patients with Laryngeal Cancer: A Systematic Review.

Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors of the head and neck region, with a poor survival rate (5-year overall survival 50-80%) as a consequence of an advanced-stage diagnosis and high recurrence rate. Tobacco smoking and alcohol abuse are the main risk factors of LSCC development. An early diagnosis of LSCC, a prompt detection of recurrence and a more precise monitoring of the efficacy of different treatment modalities are currently needed to reduce the mortality. Therefore, the identification of effective diagnostic and prognostic biomarkers for LSCC is crucial to guide disease management and improve clinical outcomes. In the past years, a dysregulated expression of small non-coding RNAs, including microRNAs (miRNAs), has been reported in many human cancers, including LSCC, and many miRNAs have been explored for their diagnostic and prognostic potential and proposed as biomarkers. We searched electronic databases for original papers that were focused on miRNAs and LSCC, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. According to the outcome, 566 articles were initially screened, of which 177 studies were selected and included in the analysis. In this systematic review, we provide an overview of the current literature on the function and the potential diagnostic and prognostic role of tissue and circulating miRNAs in LSCC.

Treatment outcomes and cost comparisons for older adults with T4 laryngeal squamous cell cancer.

To evaluate treatment modalities of T4 larynx cancer in older adults using SEER-Medicare. The database was queried for patients aged 66 and older with nonmetastatic T4 laryngeal squamous cell cancer from 2006 to 2015. Treatment modalities compared were surgery plus chemoradiation (SCR), surgery plus radiation (SR), chemoradiation (CR), surgery (S), and radiation (R). Multivariate analysis and Kaplan-Meier methods were used to explore the relationship of treatment modality and survival. Total cancer-related costs were calculated. A total of 438 patients met inclusion criteria. Patients receiving CR or SR had similar CSS to SCR (HR 1.36 and HR 1.24, respectively). Those receiving S (HR 2.00) or R (HR 2.41) had significantly worse CSS. Similar findings were observed for OS. Cancer care-related costs were not significantly different but highest in SCR ($162215) and lowest in R ($121421). Older patients with T4 larynx cancer had similar survival rates when treated with CR, SR, and SCR. Average total health care costs were not significantly different between modalities. Patients not eligible for triple-modality could consider these other treatment options.

CircBFAR correlates with poor prognosis and promotes laryngeal squamous cell cancer progression through miR-31-5p/COL5A1 axis.

Laryngeal squamous cell cancer (LSCC) is a highly malignant tumor originating from the respiratory system. Circular RNAs have been reported to be associated with the treatment and prognosis of a variety of cancers, including LSCC. The expression of circBFAR, miR-31-5p, and collagen type V alpha 1 chain (COL5A1) in LSCC tissues and cells was detected by quantitative real-time polymerase chain reaction. Cell counting kit 8 and 5-Ethynyl-2'-deoxyuridine assays were used to detect cell proliferation. Wound healing assay and transwell assay were used to test cell migration and invasion, respectively. The protein expression in LSCC cells was detected with western blot. The relationships between miR-31-5p and circBFAR or COL5A1 were identified by dual-luciferase reporter assay, RNA-pull down assay, and immunoprecipitation assay. The effect of circBFAR on tumor growth in vivo was detected by tumor xenograft mice experiment. The protein expression of COL5A1 and KI-67 in LSCC tissues was measured by immunohistochemistry assay. CircBFAR was increased in LSCC tissues and cells, and was related to advanced clinical stage and overall survival of LSCC patients. The cell viability and proliferation were inhibited by circBFAR knockdown and silencing of circBFAR blocked migration and invasion of LSCC cells. CircBFAR knockdown suppressed cell tube formation, and the protein expression of KI-67, matrix metallopeptidase 2 (MMP2), and vascular endothelial growth factor A (VEGFA) in LSCC cells. MiR-31-5p was the target of circBFAR, and the inhibitory effects of circBFAR deficiency on viability, proliferation, migration, invasion, tube formation and the protein expression of KI-67, MMP2, and VEGFA in LSCC cells were rescued by miR-31-5p downregulation. COL5A1 was negatively regulated by miR-31-5p, and was boosted in LSCC tissues and cells. COL5A1 overexpression reversed the inhibitory effects of miR-31-5p on LSCC cells. CircBFAR insufficiency hindered tumor growth in vivo. CircBFAR, miR-31-5p, and COL5A1 in LSCC progression might provide novel therapeutic targets for LSCC clinical intervention.

Paired Box 5-Induced LINC00467 Upregulation Promotes the Progression of Laryngeal Squamous Cell Cancer by Triggering the MicroRNA-4735-3p/TNF Alpha-Induced Protein 3 Pathway.

LINC00467 was reported as an oncogenic gene in different types of human cancers. In this study, we investigated the molecular mechanisms of LINC00467 in the tumorigenesis of laryngeal squamous cell cancer (LSCC). RT-qPCR was utilized to detect the mRNA expression of genes, and western blot assay was used to determine the protein levels of TNF alpha-induced protein 3 (TNFAIP3). The cell viability was detected by CCK-8 assay. Transwell assays were conducted to determine the cell migration and invasion of LSCC cells, and the cell cycle was assessed by flow cytometry. The association between paired box 5 (PAX5), LINC00467, miR-4735-3p, and TNFAIP3 was verified using ChIP, RNA pull-down, or luciferase reporter assays. In our study, we found that LINC00467 was upregulated in LSCC, and knockdown of LINC00467 suppressed cell viability and metastasis of LSCC. Besides, LINC00467 transcription could be activated by PAX5 in LSCC. Furthermore, LINC00467 acted as competitive endogenous RNA (ceRNA) for miR-4735-3p to accelerate LSCC progression. In the meantime, TNFAIP3 was identified as a downstream gene of miR-4735-3p. Finally, TNFAIP3 overexpression could overturn the effects of miR-4735-3p mimic on LSCC cellular activities. In conclusion, our results demonstrated that PAX5-induced LINC00467 facilitated LSCC progression by inhibiting miR-4735-3p to increase TNFAIP3 expression.

Differentially expressed genes related to lymph node metastasis in advanced laryngeal squamous cell cancers.

Understanding the molecular mechanisms and gene expression in laryngeal squamous cell carcinoma (LSCC) may explain its aggressive biological behavior and regional metastasis pathways. In the present study, patients with locally advanced LSCC tumors were examined for differential gene expression in the normal mucosa (non-tumoral mucosa), tumors and lymph node tissues. The aim was to identify possible predictive genes for lymph node metastasis. A total of 16 patients who had undergone total laryngectomy with neck dissection for advanced LSCC were randomly selected from a hospital database: Eight of the patients had lymph node metastasis (Group 1) and the other eight patients did not have metastasis (Group 2). Overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) were analyzed. For each patient, paraffin-embedded tissue samples were collected from non-tumoral mucosa, tumoral lesions and lymph node tissues. RNA was extracted from the tissue samples and used for complementary DNA synthesis, and microarray analysis was subsequently performed on each sample. Gene expression levels were determined in each specimen, and Groups 1 and 2 were compared and statistically analyzed. The microarray results for lymph node metastasis-positive and -negative groups, indicated the differential expression of 312 genes in the lymph nodes, 691 genes in the normal mucosal tissue and 93 genes in the tumor tissue. Transgelin (TAGLN) and cofilin 1 (CFL1) were identified as possible target genes and validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The RT-qPCR results for TAGLN and CFL1 supported the microarray data. OS, DFS and DSS times were longer in Group 2 than in Group 1 (P=0.002, 0.015 and 0.009, respectively). In addition, TAGLN and CFL1 were associated with DFS and DSS. On the basis of these results, it is suggested that TAGLN and CFL1 expression may play an important role in the pathogenesis of regional metastasis and poor prognosis in advanced LSCC.

Liposome Nanoparticles Carrying miR-22 Suppress Proliferation, Invasion and Epithelial–Mesenchymal Transition (EMT) of Laryngeal Squamous Cell Carcinoma by Targeting Wingless-Related Integration Site (WNT) Pathway

Abnormal miR-22 level is related to laryngeal squamous cell carcinoma (LSCC) progression. This study mainly assessed its role in proliferation, invasion and EMT of LSCC and their possible mechanisms of action. HN4 was collected, and corresponding groups were set as; blank group, positive control group, miR-22 group and MIRNA-22 NC group. Pathway inhibitor group and pathway agonist group were also set. The expressions of miR-22, EMT-related genes, cell proliferation rate, invasion rate, β-catenin and Cyclin D1 were observed. Results revealed that, expressions of miR-22 and e-cadherin were higher in the blank group and miR-22 NC group, while N-cadherin and Vimentin levels were lower. Moreover, miR-22 and EMT-related genes in the positive control group and miR-22 group were opposite (P &lt;0.05). The proliferation rate and invasion rate of blank and miR-22 NC groups were also lower, while positive control and miR-22 groups showed different changes (P &lt;0.05). β-catenin and Cyclin D1 expressions in the blank group and miR-22 NC group were increased compared to other two groups. The proliferation rate, invasion rate, expression of N-cadherin and Vimentin were higher and E-cadherin was lower in blank and pathway agonist group, which was opposite in the pathway inhibitor group (P &lt; 0.05). β-catenin and Cyclin D1 protein levels in blank and pathway agonist groups were higher than pathway inhibitor group (P &lt; 0.05). A binding region between miR-22 gene sequence and 3′UTR 215-229 sequence of Wnt gene was found and Wnt was found to be the target gene for miR-22. The fluorescence intensity of mutant plasmid was higher than wild-type plasmid (P &lt;0.05). miR-22 can inhibit LSCC proliferation, invasion and EMT and the main mechanism of action is related to the Wnt signaling pathway. MiR-22 targeted Wnt gene and inhibited Wnt signaling pathway activity, lower key factor beta catenin expression Wnt pathways, thereby inhibiting factor laryngeal squamous cancer cells proliferation, Cyclin D1 expression, resulting in inhibition of cell proliferation, and EMT process at the same time, reducing the cell invasion ability, inhibiting the growth of laryngeal squamous cancer cells. Eventually, the Wnt pathways or miR-22 all can be used as targets for laryngeal squamous carcinoma.

Induction chemotherapy using carboplatin and paclitaxel followed by hypofractionated radiation therapy in locally advanced hypopharyngeal and laryngeal squamous cell cancer.

e18039 Background: Head and neck cancer (HNC) is one of the most common cancers in Pakistan due to excessive use of chewable tobacco. Locoregional control is not optimum due to advanced stage at presentation and suboptimal cancer treatment facilities. Innovations in treatment schedules are of utmost importance to tackle the problem of overburden of patients and shortage of resources for radiation therapy in the country. The aim of the study is to assess the efficacy of induction chemotherapy with carboplatin and paclitaxel (CP) followed by hypofractionated radiotherapy (HRT) in patients with locally advanced laryngeal and hypopharyngeal cancers. Methods: A total of 68 patients with biopsy proven HNC were included. Patients having primary tumor in larynx (35) and hypopharynx (33) with TNM stage III to IVB were selected. The patients were planned for three cycles of CP every three weeks in a dose of AUC = 5 and 175 mg/m² on day 1 of each cycle respectively. After three cycles of chemotherapy, patients were planned for hypofractionated radiotherapy (HRT). A total of 55 Gray (Gy) was planned with 2.75 Gy per fraction and five fractions a week. Spinal cord dose was limited to 33 Gy. Response Evaluation Criteria in Solid Tumor (RECIST) was used to assess various response rates using computed tomography (CT) six weeks after completion of HRT. Patients were followed for a median of 27.4 months to assess disease free survival (DFS) and overall survival (OS). Results: 61 patients (90%) were available for assessment. Others were excluded due to inability to complete the planned treatment. Eight patients (12%) showed disease progression during treatment and were switched to other form of treatment. Seven patients (10%) showed grade 3 mucosal toxicity and needed treatment interruption. Thirteen patients (19%) showed hematological related grade 1-2 toxicity. The complete response (CR) was seen in 18 (35%), partial response (PR) in 27 (52%) and stable disease SD in 7 (13%) patients. Three year DFS and OS were 45% and 58% respectively. Mean and median DFS (year) were 3.67±0.13 (95% confidence interval [CI] 3.19-3.94) and 4.24±0.43 (CI 3.46-4.52) respectively. Mean and median OS (year) were 3.89±0.11 (CI 3.72-4.15) and 4.12±0.23 (CI 3.87-4.38) respectively. Conclusions: Induction CP followed by HRT is a reasonable in locally advanced laryngeal and hypopharyngeal cancer. A larger phase III randomized trial will be better to define its role before routinely recommending this schedule in these patients.

Photothermolysis Mediated by Gold Nanorods Conjugated with Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody Induces Apoptosis via the Mitochondrial Apoptosis Pathway in Laryngeal Squamous Cell Cancer.

Gold nanorods (AuNRs) have unique optical properties and biological affinity and can be used to treat tumors when conjugated with other protein molecules. Our previous studies have shown that EGFR monoclonal antibody (EGFRmAb)-modified AuNRs exert strong antitumor activity in vitro by inducing apoptosis. In this study, we tested the effects of EGFRmAb-modified AuNRs on laryngeal squamous cell cancer (LSCC) in vitro and in vivo. The in vitro results showed that EGFRmAb-modified AuNRs inhibited NP-69, BEAS-2B and Hep-2 cell growth and induced mitochondria-dependent apoptosis. The mitochondrial membrane potential was reduced, leading to the release of cytochrome C (Cyt C) and consequent activation of the intrinsic mitochondrial apoptosis pathway. Moreover, we observed that the occurrence of mitochondrial apoptosis is related to the destruction of the lysosome-mitochondria axis. To verify the effects in vivo, we also established a laryngeal tumor model in nude mice by subcutaneous transplantation. In model mice treated with EGFRmAb-modified AuNRs and irradiated with an NIR laser, tumor cell apoptosis and tumor growth were inhibited. These results suggest that EGFRmAb-modified AuNRs induced apoptosis through the intrinsic mitochondrial apoptotic pathway and are a potential candidate for cancer therapy.

Filamin-A expression in laryngeal squamous cell carcinoma and its clinical significance.

Laryngeal squamous cell carcinomas (LSCCs) are tumours with a high incidence of treatment failure and recurrence. Recent strategies to improve the five-year survival rate and to decrease the rates of recurrence and metastases did not improve outcomes significantly. Research efforts in recent years have started focusing on discovering biomarkers of prognosis and management in LSCCs. Filamin-A reportedly has been associated with metastatic disease in a recent study. Analysis of this protein's expression in LSCCs is lacking in the literature. This study analysed the expression of filamin-A, using immunohistochemistry, in a tissue microarray of 80 cases of laryngeal squamous cell cancers. Clinical-pathological parameters were analysed according to filamin-A expression in the tissue microarray. Furthermore, a review of possible mechanisms of this protein in cancer, in general, was presented, along with a review of the protein's expression in other head and neck tumours. A significant majority of laryngeal squamous cell cancers exhibited positive expression of filamin-A protein. All the filamin-A positive tumours expressed it in their cytoplasm. Significant correlation between filamin-A expression and grade, stage, lymph node status and metastases were found. The above may suggest an important role for filamin-A in LSCCs. Overall, filamin-A expression in laryngeal cancer is in line with evidence seen in other head and neck cancers. Further studies are in order to pinpoint the exact role of this protein in LSCCs, and its possible utilization in the management of these difficult-to-treat tumours.

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

SummaryAlcohol 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 β 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.

Trends in Laryngeal Squamous Cell Cancer Treatment of the Elderly in Our Hospital from 2007 to 2018

Trends in Laryngeal Squamous Cell Cancer Treatment of the Elderly in Our Hospital from 2007 to 2018

Patterns of Failure After Definitive Treatment of T4a Larynx Cancer.

Recurrence is known to predict laryngeal squamous cell cancer (LSCC) survival. Recurrence patterns in T4a LSCC are poorly characterized and represent a possible explanation for observed survival discrepancies by treatment rendered. Retrospective database review. Veterans Affairs national database. Patients with T4a LSCC between 2000 and 2017 were identified and stratified by treatment (chemoradiotherapy [CRT] vs total laryngectomy + neck dissection + adjuvant therapy [surgical]). Primary outcomes were locoregional and distant recurrence. Secondary outcomes of overall mortality, larynx cancer mortality, and noncancer mortality were evaluated in Cox and Fine-Gray models. A total of 1043 patients had comparable baseline demographics: 438 in the CRT group and 605 in the surgical group. Patients undergoing CRT had higher proportions of node positivity (64.6% vs 53.1%, P < .001). Locoregional and distant recurrence were less common in the surgical group (23.0% vs 37.2%, P < .001; 6.8% vs 13.3%, P < .001, respectively); however, distant metastatic rates did not differ within the N0 subgroup (P = .722). On multivariable regression, surgery demonstrated favorable locoregional recurrence (hazard ratio [HR], 0.49; 95% CI, 0.39-0.62; P < .001), distant recurrence (HR, 0.47; 95% CI, 0.31-0.71; P < .001), overall mortality (HR, 0.75; 95% CI, 0.64-0.87; P < .001), and larynx cancer mortality (HR, 0.69; 95% CI, 0.56-0.85; P < .001). T4a LSCC survival discrepancies between surgical and nonsurgical treatment are influenced by varying recurrence behaviors. Surgery was associated with superior disease control and improved survival. Beyond the known benefit in locoregional control with surgery, there may be a protective effect on distant recurrence that depends on regional disease burden.

Perineural Invasion as a Prognostic Factor in Laryngeal Squamous Cell Cancer: A Matched-Pair Survival Analysis

Background The purpose of this study was to compare survival outcomes in patients with perineural invasion (PNI)-positive laryngeal squamous cell carcinoma (LSCC) and patients with PNI-negative LSCC. Methods A total of 1,272 patients with LSCC, diagnosed between 2008 and 2017, were included in this study. LSCC Patients with and without PNI were matched based on possible confounding factors. Survival analysis was performed using Kaplan–Meier estimates and the Cox proportional hazards model. Results Of the 1,272 LSCC patients, 118 (9.28%) were positive for PNI. Compared to PNI-negative patients, PNI-positive LSCC patients had significantly worse overall survival (OS) (p = 0.017), disease-specific survival (DSS) (p = 0.034) and recurrence-free survival (RFS) (p = 0.002). After pair matching, cohorts consisted of 118 patients in the PNI-positive group and 118 in the PNI-negative group. Significantly increased risk of OS (HR, 2.17; 95% confidence interval [CI], 1.29–3.61, p = 0.003), DSS (HR, 2.07; 95% CI, 1.32–3.24, p = 0.004) and RFS (HR, 2.65; 95% CI, 1.59–4.40, p < 0.001) was observed after adjustment for prognostic variables. Conclusions Patients with PNI-positive LSCC have significantly worse survival outcomes compared to patients with PNI-negative LSCC.

Hsa_circ_0006232 promotes laryngeal squamous cell cancer progression through FUS-mediated EZH2 stabilization

ABSTRACT Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors in head and neck tumors. Our previous study has revealed that hsa_circ_0006232 is abnormally expressed in LSCC. This study attempts to verify the biological role of hsa_circ_0006232 in LSCC. We found that compared with human bronchial epithelial cells, hsa_circ_0006232 was highly expressed in human LSCC cells (AMC-HN-8 and TU686). Moreover, hsa_circ_0006232 promoted proliferation, migration and invasion of AMC-HN-8 and TU686 cells. Hsa_circ_0006232 promoted the expression of enhancer of zeste homolog 2 (EZH2) and repressed the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Fused in sarcoma (FUS) interacted with hsa_circ_0006232 and EZH2, and FUS promoted the stabilization of EZH2. Hsa_circ_0006232 inhibited PTEN by promoting FUS expression. Moreover, we constructed a tumor xenograft model by injection of AMC-HN-8 cells with hsa_circ_0006232 knockdown, and we found that hsa_circ_0006232 deficiency decreased tumor growth in mice. Hsa_circ_0006232 silencing repressed EZH2 expression and enhanced PTEN expression in tumor tissues. In conclusion, our data have demonstrated that Hsa_circ_0006232 promotes proliferation, migration and invasion of LSCC cells, and accelerates tumor growth of LSCC through FUS-mediated EZH2 stabilization. Thus, hsa_circ_0006232 may be a novel therapeutic target in LSCC treatment.