Laryngeal Cancer Research Articles

Psychological Well-Being and Quality of Life in Laryngeal Cancer Patients across Tumor.

Background/Objectives: Laryngeal cancer significantly impacts patients' psychological well-being and quality of life (QoL). This study aims to evaluate the psychological impact and QoL in patients with laryngeal cancer, focusing on differences based on tumor stage and treatment. Methods: This longitudinal study included 75 patients diagnosed with laryngeal cancer. Participants were assessed at diagnosis and 3 months post-treatment using validated tools such as the Hospital Anxiety and Depression Scale (HADS) and the EORTC QLQ-H&N35 questionnaire. This study analyzed the impact of tumor stage, treatment type, and demographic factors on psychological well-being and QoL. Results: Patients with early-stage tumors (Stage I) reported significantly better psychological well-being and QoL compared to those with more advanced tumors (Stages III and IV) both before and after treatment. The non-significant p-values in advanced stages suggest a uniformity of severe distress and poor QoL among these patients. Treatment led to significant reductions in anxiety and depression in early-stage patients, while those with advanced-stage disease showed less improvement. Conclusions: The findings highlight the critical need for early psychological intervention, particularly in advanced-stage laryngeal cancer patients who continue to experience substantial psychological distress and poor QoL despite treatment. Integrating comprehensive psychological support into standard care is essential to improve overall outcomes for these patients.

Golgi-localized Ring Finger Protein 121 is necessary for MYCN-driven neuroblastoma tumorigenesis

MYCN amplification predicts poor prognosis in childhood neuroblastoma. To identify MYCN oncogenic signal dependencies we performed N-ethyl-N-nitrosourea (ENU) mutagenesis on the germline of neuroblastoma-prone TH-MYCN transgenic mice to generate founders which had lost tumorigenesis. Sequencing of the mutant mouse genomes identified the Ring Finger Protein 121 (RNF121WT) gene mutated to RNFM158R associated with heritable loss of tumorigenicity. While the RNF121WT protein localised predominantly to the cis-Golgi Complex, the RNF121M158R mutation in Helix 4 of its transmembrane domain caused reduced RNF121 protein stability and absent Golgi localisation. RNF121WT expression markedly increased during TH-MYCN tumorigenesis, whereas hemizygous RNF121WT gene deletion reduced TH-MYCN tumorigenicity. The RNF121WT-enhanced growth of MYCN-amplified neuroblastoma cells depended on RNF121WT transmembrane Helix 5. RNF121WT directly bound MYCN protein and enhanced its stability. High RNF121 mRNA expression associated with poor prognosis in human neuroblastoma tissues and another MYC-driven malignancy, laryngeal cancer. RNF121 is thus an essential oncogenic cofactor for MYCN and a target for drug development.

Postoperative pathological findings and prognosis of early laryngeal and pharyngeal cancer treated with transoral surgery

ObjectiveTransoral surgery for early-stage pharyngeal and laryngeal cancer provides good local control and is less invasive than external incisions. Postoperative pathological findings are considered the most important indicators for determining postoperative treatment, but detailed criteria have not been established. In this study, we evaluated the impact of postoperative pathological findings on prognosis of patients undergoing transoral surgery. MethodsThis study included patients with oropharyngeal, hypopharyngeal, and supraglottic cancer who underwent transoral surgery at Gifu University Hospital from April 2016 to December 2023. Resection margins were pathologically evaluated with horizontal and vertical margins, and vascular invasion was evaluated in three categories: lymphatic invasion, venous invasion, and perineural invasion. The correlation between each postoperative pathological finding and prognosis was evaluated. ResultsA total of 70 cases were assessed in this study. Cases of horizontal margin positive were 38.6 %, and cases of vertical margin positive were 27.1 %. Prognoses were comparable to previous reports. Despite the high margin positive rate, the 5-year overall survival rate was 77.1 %. The 5-year disease-specific survival rate was 89.7 %, and the 5-year local control rate was 85.3 %. Notably, when evaluated by margin direction, cases with positive horizontal margins had significantly worse prognoses. Although no significant correlation was found between vascular invasion and prognosis, cases of venous invasion tended to have a higher local recurrence rate. ConclusionThis study suggests that transoral surgery has good prognosis despite a high positive-margin rate. However, detailed criteria for additional treatment have not been developed, and further case accumulation is required. Intriguingly, positive horizontal margins are correlated with significantly worse prognosis. This result may be related to a high risk of multiple cancers, and careful follow-up after surgery is recommended.

Analysis of Risk Factors with Assessment of the Impact of the Microbiome on the Risk of Squamous Cell Carcinoma of the Larynx.

Introduction: Head and neck squamous cell carcinoma (HNSCC) ranks sixth among cancers in the world, and the 5-year survival rate ranges from 25% to 60%. The risk factors for HNSCC are primarily smoking, alcohol consumption and human papillomavirus (HPV). Data indicate that 15-20% of cancers are caused by infectious agents, 20-30% by smoking and 30-35% by unhealthy lifestyles, diet, lack of physical activity and obesity. Dysbiosis is a microbiome imbalance, which promotes oncogenesis by intensifying inflammatory processes and affecting the host's metabolism. Profiling the microbiome in various types of cancer is currently the subject of research and analysis. However, there is still little information on the correlation of the microbiome with HNSCC and its impact on oncogenesis, the course of the disease and its treatment. Objective: The aim of the study was to prospectively assess risk factors with assessment of the impact of the microbiome on the risk of squamous cell carcinoma of the larynx. The study included a group of 44 patients diagnosed with squamous cell carcinoma of the larynx and 30 patients from the control group. Results: In the control group, bacteria of the normal microbiome dominated-the genus Streptococcus, Gemella, Neisseria and Kingella. In the group of patients with laryngeal cancer, Prevotella, Clostridiales and Stomatobaculum were found significantly more often. Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia odontolytica were also found at a higher percentage in the study group. Analyzing the phylum, Firmicutes dominated in the control group; there were statistically significantly more of them than in patients from the study group. Bacteroides and Bacillota were found significantly more often in patients with laryngeal cancer. Conclusions: The importance of the microbiome in oncology has been confirmed in many studies. Independent risk factors for laryngeal cancer were primarily a lower number of Firmicutes in the microbiome, but also an increased leukocyte level above 6.52 × 103/mm and a decreased total protein level below 6.9 g/dL. Prevotella, Clostridiales, Stomatobaculum, Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia were considered to be the bacteria contributing to the development of laryngeal cancer. Streptococcus, Gemella, Neisserie and Kingella were considered to be protective bacteria. Moreover, the study confirmed the significant impact of smoking, alcohol consumption and poor oral hygiene on the development of laryngeal cancer. The microbiome, its identification and manipulation may constitute a breakthrough discovery for improving the diagnosis and oncological therapy of laryngeal cancer, and also of the entire group of HNSCC. Profiling the microbiome may allow for personalized therapy related to its modification. Assessing the microbiome of patients diagnosed with cancer may provide an opportunity to predict treatment response and effectiveness.

Diagnostic Performance of Computed Tomography in Laryngeal Carcinoma and its Extension

Background: Laryngeal carcinoma is a common malignant neoplasm of the head and neck with high incidence of new malignancies worldwide every year. Several imaging techniques including magnetic resonance imaging (MRI) and computed tomography (CT) scans are widely used to detect laryngeal carcinoma. Of them, CT scan is relatively cheaper, easily available and sensitive in the evaluation of laryngeal carcinoma. Objective: To find out the diagnostic performance of CT scan in laryngeal carcinoma and its extensions. Methodology: This cross-sectional study was carried out in the department of Radiology and Imaging, Dhaka Medical CollegeHospital, Dhaka, during the period of July, 2016 to June, 2018 for a period of 2(two) years. A total of 50 samples were included purposively. The enrolled patients were attending outpatient department (OPD) or admitted in indoor and referred to the Radiology and Imaging department for CT scan. All the enrolled cases had laryngectomy and resected tissues were sent for histopathological examination. Data collection was done by the principal investigator and a preformed questionnaire was used during data collection. Following completion of data collection, it was analyzed by SPSS 20.0. Results: Age range of the patients was from 18 to 84 years, with the mean age of 61.2 years + 13.4 years standard deviation and a male-female ratio of about 7.3:1. By multidetector CT scan, majority (32, 64.00%) of the tumours were found confined in a specific area with no extension, followed by 12 (24.00%) involving both supraglottic and glottic region. On the other hand, by histopathology, almost all (47, 94.00%) of the cases were found malignant and majority of the malignant cases (31, 65.96%) were found without nodal metastasis. Validity tests of CT in the diagnosis of laryngeal carcinoma revealed sensitivity, specificity, accuracy and positive predictive values of 97.9%, 66.7%, 96% and 97.9% respectively. In case of nodal metastases, the sensitivity, specificity, accuracy and positive predictive value were 93.8%, 97%, 96% and 93.8% respectively. Conclusion: Contrast enhanced CT scan has good role in detecting nodal metastases, but had complementary role in detecting laryngeal carcinoma. Journal of Monno Medical College December, 2023; 9 (2): 63-67

Study of the significance of the combination of the fibrinogen-albumin ratio and sarcopenia in predicting the prognosis of laryngeal cancer patients undergoing radical surgery

ObjectiveThis study aims to investigate how the impact of preoperative sarcopenia and inflammatory markers for laryngeal cancer patients and develop a new scoring system to predict their prognosis.Materials and methodsPatients who underwent laryngectomy for laryngeal cancer (LC) from December 2015 to December 2020 at the Second Affiliated Hospital of Fujian Medical University were included. Independent prognostic factors were determined using univariate and multivariate analyses. A new scoring system (SFAR) was established based on FAR and preoperative sarcopenia, and statistically analyzed.Results198 cases included in this study that met the admission criteria. Multivariate analysis shown that preoperative sarcopenia, pTNM stage, and FAR were independent prognostic factors for laryngeal cancer. Based on these three indicators, we developed the SFAR scoring system. Multivariate analysis showed that SFAR was an independent predictor of laryngeal cancer (p < 0.001). SFAR was then incorporated into a prognostic model that included T-stage and N-stage, and a column-line graph was generated to accurately predict its survival.ConclusionSystemic inflammation and sarcopenia are significantly associated with postoperative prognosis in laryngeal cancer. A new scoring system (SFAR) had implications for improving the prognosis of patients undergoing surgery for laryngeal cancer.

Personalized Treatment Strategies via Integration of Gene Expression Biomarkers in Molecular Profiling of Laryngeal Cancer.

Laryngeal cancer poses a substantial challenge in head and neck oncology, and there is a growing focus on customized medicine techniques. The present state of gene expression indicators in laryngeal cancer and their potential to inform tailored therapy choices are thoroughly examined in this review. We examine significant molecular changes, such as TP53, CDKN2A, PIK3CA, and NOTCH1 mutations, which have been identified as important participants in the development of laryngeal cancer. The study investigates the predictive and prognostic significance of these genetic markers in addition to the function of epigenetic changes such as the methylation of the MGMT promoter. We also go over the importance of cancer stem cell-related gene expression patterns, specifically CD44 and ALDH1A1 expression, in therapy resistance and disease progression. The review focuses on indicators, including PD-L1, CTLA-4, and tumor mutational burden (TMB) in predicting immunotherapy responses, highlighting recent developments in our understanding of the intricate interactions between tumor genetics and the immune milieu. We also investigate the potential for improving prognosis accuracy and treatment selection by the integration of multi-gene expression panels with clinicopathological variables. The necessity for uniform testing and interpretation techniques is one of the difficulties, in implementing these molecular insights into clinical practice, that are discussed. This review seeks to provide a comprehensive framework for promoting personalized cancer therapy by combining the most recent data on gene expression profiling in laryngeal cancer. Molecularly guided treatment options may enhance patient outcomes.

Current Status of Robotic Surgery for Pharynx and Larynx Cancers

Current Status of Robotic Surgery for Pharynx and Larynx Cancers

Nasopharyngeal, tongue and laryngeal cancer in Southern Ethiopia: a seven-year retrospective cross-sectional review

Nasopharyngeal, tongue and laryngeal cancer in Southern Ethiopia: a seven-year retrospective cross-sectional review

Primary Small Cell Neuroendocrine Carcinoma of Larynx: An Atypical Case Presentation

Neuroendocrine tumors account for &lt;1% of all malignant tumors that can originate from any part of the body, most frequently diagnosed in the lung. Extrapulmonary presentation is rare, common sites are genitourinary and gastrointestinal. According to the 2017 WHO proposed classification, small cell type (SCNEC) is a poorly differentiated neuroendocrine carcinoma. The most common site in the head and neck is the larynx, accounts for &lt;0.6%. Small cell neuroendocrine carcinomas are extremely rare entity of laryngeal cancers. We report a case of small cell neuroendocrine carcinoma of larynx.

Retracted: Boschniakia rossica Polysaccharide Triggers Laryngeal Carcinoma Cell Apoptosis by Regulating Expression of Bcl-2, Caspase-3, and P53.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Chunping Yao, Xiujuan Cao, Zheng Fu, Jing Tian, Wei Dong, Jin Xu, Kang An, Limin Zhai, Jinming Yu. Boschniakia rossica Polysaccharide Triggers Laryngeal Carcinoma Cell Apoptosis by Regulating Expression of Bcl-2, Caspase-3, and P53. Med Sci Monit, 2017; 23: 2059-2064. DOI: 10.12659/MSM.901381.

Comparing Closure Techniques for Pharyngeal Mucosa After Total Laryngectomy: Manual Suture, Linear Stapler, and Thyroid Gland Flap-A Retrospective Analysis.

Objective: This study aimed to compare the clinical effectiveness of manual suture (group A), linear stapler (group B), and thyroid gland flap (group C) for pharyngeal mucosal closure after total laryngectomy (TL) in laryngeal cancer patients. Methods: The data of laryngeal cancer patients who underwent TL between January 1, 2017, and December 1, 2021, were analyzed. Patients were categorized into group A, group B, and group C based on the closure technique. Various parameters, including general data, hospitalization days, total cost, pharyngeal closure time, pharyngeal fistula, pre- and post-surgical calcium levels, and thyroid function indexes, were compared. Results: The study included 81 patients (mean age: 64.09 ± 9.20 years), the general data of the 3 groups of patients were comparable. Tumor stage and primary tumor location varied significantly among the groups (P = .002 and P < .001, respectively). Group A was more commonly used for advanced-stage tumors with widespread invasion. Group B was primarily used for early-stage tumors localized to the larynx. Group C was preferred for cases with mucosal defects or extensive hypopharyngeal invasion. Group B presented a significantly shorter operation time and slightly lower total cost (P = .006). Pharyngeal fistula incidence was 17.28% (14/81), with comparable rates among the groups [12.35% (10/50) in group A, 12.5% (2/16) in group B, and 13.3% (2/15) in group C]. No dysphagia complications were observed during the 2-to-5-year follow-up. Blood calcium levels and thyroid function indicators showed no significant differences before and after surgery among the 3 groups (P > .05). Conclusion: Thyroid gland flap is a safe option that can be used to repair mucosal defects and close the pharyngeal cavity after TL surgery, but in the absence of mucosal defects and widespread tumor invasion, linear staplers are the most time-efficient method.

Primary Site Influences the Ability of Magnetic Resonance Imaging to Assess Cartilage Invasion in Advanced Laryngeal Cancer.

Accurate staging of advanced laryngeal cancer is important, as treatment can vary significantly between larynx preservation and total laryngectomy. The purpose of this study was to evaluate the accuracy of magnetic resonance imaging (MRI) in assessing features of T4a disease in locally advanced laryngeal cancer and determine if primary site played a role in the accuracy of MRI in this setting. A retrospective cohort study of patients undergoing a total laryngectomy in a tertiary referral center for head and neck cancer over a 10-year time period was carried out. Patients met inclusion criteria if they underwent a primary total laryngectomy for squamous cell carcinoma (SCC) of the larynx during the study period. Data collected included basic demographic data, primary tumor subsite, and clinical and pathological staging. The predictive ability of MRI on outer thyroid cortex invasion, extralaryngeal extension, and overall T4a stage was analyzed with receiver operating characteristics analysis. Analysis was compared to histological data on outer thyroid cortex invasion, extralaryngeal extension, and histological T4a stage. A total of 112 patients met inclusion criteria. The mean age of the cohort was 65.1. Glottic primary subsite was associated with a statistically significant elevated risk for histological outer cortex erosion (p = 0.006), but MRI demonstrated worse sensitivity in detecting this outer cortex invasion in glottic primaries(p = 0.002). Glottic primaries tumors display an increased likelihood of thyroid cartilage invasion, however, MRI demonstrates a poorer sensitivity for detecting these features. Level 3 Laryngoscope, 2024.

Meta-Analysis of the Relationship Between Occupational/Environmental Exposure to Wood Dust and Laryngeal Cancer.

Wood dust is a human carcinogen. However, studies examining the relationship between wood dust exposure and laryngeal cancer have yielded inconsistent findings. Therefore, we systematically reviewed relevant studies examining the relationship between wood dust exposure and laryngeal cancer development, followed by a meta-analysis. Publications in the following databases were searched: PubMed, Medline, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). The Newcastle-Ottawa scale was used to evaluate the study quality. A random-effects model was used for the meta-analysis. Eighteen case-control studies and one cohort study, involving a total of 4426 patients with laryngeal cancer and 319,129 control participants, were identified. The association between occupational/environmental exposure to wood dust and laryngeal cancer, if any, was unclear (adjusted combined OR: 1.11; 95% CI: 0.94-1.31). However, subgroup analyses according to the number of cases, geographic region, publication year, and follow-up duration revealed correlations between wood dust exposure correlated and laryngeal cancer, as follows: number of cases > 200 (OR: 1.14; 95% CI: 1.01-1.25 [n = 10]); studies conducted in the US (OR: 1.21; 95% CI: 1.07-1.37 [n = 5]); follow-up time > 5 years (OR: 1.19; 95% CI: 1.07-1.32 [n = 10]); and publication after the year 2000 (OR: 1.15; 95% CI: 1.04-1.28 [n = 8]). A high heterogeneity in the results was observed (I2 = 42.5%, p = 0.024). The results were stable, and no publication bias existed, according to sensitivity analysis. This meta-analysis suggests that wood dust exposure is associated with laryngeal cancer. Additional large-scale studies are warranted to clarify the relationship between wood dust exposure and laryngeal cancer.

Visual pathology reports for communication of final margin status in laryngeal cancer surgery

BackgroundPositive margins are frequently observed in total laryngectomy (TL) specimens. Effective communication of margin sampling sites and final margin status between surgeons and pathologists is crucial. In this study, we evaluate the utility of multimedia visual pathology reports to facilitate interdisciplinary discussion of margin status in laryngeal cancer surgery. MethodsEx vivo laryngeal cancer surgical specimens were three-dimensional (3D) scanned before standard of care pathological analysis. Using computer-aided design software, the 3D model was annotated to reflect inking, sectioning, and margin sampling sites, generating a visual pathology report. These reports were distributed to head and neck surgeons and pathologists postoperatively. ResultsFifteen laryngeal cancer surgical specimens were 3D scanned and virtually annotated from January 2022 to December 2023. Most specimens (73.3%) were squamous cell carcinomas (SCCs). Among the cases, 26.7% had final positive surgical margins, whereas 13.3% had close margins, defined as <5 mm. The visual pathology report demonstrated sites of close or positive margins on the 3D specimens and was used to facilitate postoperative communication between surgeons and pathologists in 85.7% of these cases. Visual pathology reports were presented in multidisciplinary tumor board discussions (20%), email correspondences (13.3%), and teleconferences (6.7%), and were referenced in the final written pathology reports (26.7%). Conclusions3D scanning and virtual annotation of laryngeal cancer specimens for the creation of visual pathology reports is an innovative approach for postoperative pathology documentation, margin analysis, and surgeon–pathologist communication.

Exploring the Impact of Model Complexity on Laryngeal Cancer Detection.

Background: Laryngeal cancer accounts for a third of all head and neck malignancies, necessitating timely detection for effective treatment and enhanced patient outcomes. Machine learning shows promise in medical diagnostics, but the impact of model complexity on diagnostic efficacy in laryngeal cancer detection can be ambiguous. Methods: In this study, we examine the relationship between model sophistication and diagnostic efficacy by evaluating three approaches: Logistic Regression, a small neural network with 4 layers of neurons and a more complex convolutional neural network with 50 layers and examine their efficacy on laryngeal cancer detection on computed tomography images. Results: Logistic regression achieved 82.5% accuracy. The 4-Layer NN reached 87.2% accuracy, while ResNet-50, a deep learning architecture, achieved the highest accuracy at 92.6%. Its deep learning capabilities excelled in discerning fine-grained CT image features. Conclusion: Our study highlights the choices involved in selecting a laryngeal cancer detection model. Logistic regression is interpretable but may struggle with complex patterns. The 4-Layer NN balances complexity and accuracy. ResNet-50 excels in image classification but demands resources. This research advances understanding affect machine learning model complexity could have on learning features of laryngeal tumor features in contrast CT images for purposes of disease prediction.

Laryngopharyngeal reflux: knowledge, attitudes, and practices among primary healthcare physicians.

The aim of this study was to estimate the level of knowledge, attitudes, and practices regarding laryngopharyngeal reflux (LPR) among primary healthcare (PHC) physicians in Saudi Arabia. This quantitative cross-sectional study used an online-based questionnaire distributed to physicians in PHC facilities and hospitals in Saudi Arabia. The questionnaire consisted of four sections that provided data on demographics, knowledge, attitudes, and practices. Of the 473 physicians included in the study, one-third were unaware of LPR, and two-thirds were unfamiliar with the reflux symptom index (RSI). The most common sources of LPR knowledge were textbooks and literature (49.8%). The most recognised risk factor, symptom, and complication were high body mass index (75.8%), voice problems (82.4%), and laryngeal cancer (70.6%), respectively. The most recognised diagnostic and treatment options were laryngoscopy (73.5%) and lifestyle modifications (87.3%), respectively, while only 60.4% of participants recognised proton pump inhibitors as a treatment option. Most PHC physicians believed that LPR is underdiagnosed and that primary prevention and awareness among the general population need to be improved. One in three PHC physicians knew nothing about LPR, and two in three were unfamiliar with the RSI. More than half could not recognise all major symptoms of LPR, which might be a cause for concern, as recognising these symptoms is crucial for proper diagnosis. We recommend increasing the education of physicians about LPR, its signs and symptoms, and the RSI, all of which provide valuable clues for diagnosis.

Survival Outcomes of Total Laryngectomy: Evaluating the Intersection of Race and Social Determinants.

Analyze joint effects of race and social determinants on survival outcomes for patients undergoing total laryngectomy for advanced or recurrent laryngeal cancer at a tertiary care institute. Retrospective chart review of adult patients undergoing total laryngectomy for laryngeal cancer at a tertiary care center from 2013 to 2020. Extracted data included demographics, pathological staging and features, treatment modalities, and outcomes such as recurrence, fistula formation, and 2- and 5-year disease-free survival (DFS) and overall survival (OS). Area Deprivation Index (ADI) was calculated for each patient. Among 185 patients identified, 113 were Black (61.1%) and 69 were White (37.3%). No significant differences were observed between racial groups regarding age, gender, ADI, or cancer stage. There was no significant difference in 2-year DFS/OS between groups. ADI was comparable between racial groups, with the majority in the highest deprivation quintile (63.8% of Whites vs. 62.5% of Blacks). No significant differences were observed in gender, race, cancer stage, positive margins, extracapsular extension, or smoking status among ADI quintiles. We observed a significant difference in 2-year DFS stratified by ADI (p = 0.025). Stratifying by ADI and race revealed improved survival of White patients in lower quintiles but higher survival of Black patients in the highest disparity quintile (p = 0.013). Overall, survival outcomes by race were comparable among laryngectomy patients, but there was a significant difference in 2-year DFS when stratified by ADI. Further research into survival outcomes related to social determinants is needed to better delineate their effects on head and neck cancer outcomes. 3 Laryngoscope, 2024.

CH25H Promotes Autophagy and Regulates the Malignant Progression of Laryngeal Squamous Cell Carcinoma Through the PI3K-AKT Pathway.

Laryngeal squamous cell carcinoma (LSCC) is a type of cancer of the respiratory tract that often presents with subtle symptoms at the early stage and is susceptible to recurrence and metastasis. To find out key regulatory genes involved in LSCC development, we downloaded LSCC-related sequencing datasets for bioinformatics analysis. WGCNA was performed on GSE142083 and differential analysis was conducted on GSE51985 and TCGA-HNSC. Intersectiongenes were taken from the above three datasets. To confirm the function of genes, we overexpressed and knocked down genes in cells and treated them with autophagy agonist Rapamycin and PI3K-AKT pathway inhibitor. At the cellular level, the expression of CH25H, autophagy-related proteins (LC3 I, LC3 II, p62, and Beclin 1), and PI3K-AKT pathway-related proteins (PI3K, AKT, and p-AKT) were assessed via Western blot; the mRNA level of CH25H was evaluated through qRT-PCR; the cell activity was examined by CCK8; the apoptosis was assessed through flow cytometry; and the cell migration and invasion were assessed through wound healing and Transwell assays. Through bioinformatics analysis, we screened 7 genes (CH25H, NELL2, STC2, TMEM158, ZIC2, HOXD11, and HOXD10). Ultimately, CH25H was selected for follow-up experiments. By detecting CH25H expression in human immortalized keratinocytes (HaCaT) and LSCC cells (Tu-686, SNU899, and AMC-HN-8), it was found out that CH25H expression was higher in HaCaT cells than in LSCC cells. To elucidate the role of CH25H in LSCC development, we overexpressed CH25H in Tu-686 cells and downregulated its expression in AMC-HN-8 cells. CH25H was revealed to reduce the proliferation, activity, invasion, and migration of LSCC cells while increasing their apoptosis levels. Significant changes were also observed in the expressions of autophagy- and PI3K-AKT pathway-related proteins. To further investigate the roles of autophagy and the PI3K-AKT pathway in LSCC development, we respectively employed autophagy agonists and inhibitors targeting the PI3K-AKT pathway to intervene the cells, and found that CH25H regulated the PI3K-AKT pathway to promote autophagy, thus enhancing the apoptosis of LSCC cells. We further investigated CH25H's impact on tumor growth, autophagy, and the PI3K-AKT pathway at the animal level and found that CH25H promoted autophagy of LSCC cells and inhibited the PI3K-AKT pathway, and ultimately inhibiting the progression of LSCC. In summary, CH25H promotes autophagy and affects the malignant progression of LSCC through the PI3K-AKT pathway.

Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses

BackgroundAntibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity.MethodsThis study examined the therapeutic efficacy and potential mechanisms of...