Laryngeal Squamous Cell Carcinoma Research Articles

A Systematic Review of Circulating miRNAs Validated by Multiple Independent Studies in Laryngeal Cancer

Background and Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer with significant morbidity and mortality. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for cancer diagnosis and prognosis. This systematic review aims to identify circulating miRNAs associated with LSCC, emphasizing those validated by at least two independent studies to improve reliability and clinical applicability. Methods: An extensive literature search was performed in the PubMed, Scopus, and Web of Science databases up to October 2024, using keywords related to LSCC and circulating miRNAs. Studies involving human participants that provided quantitative data on circulating miRNA expression levels and their clinical correlations were included. Data extraction and quality assessment were conducted following standardized protocols, highlighting miRNAs reported in multiple studies. Results: Nine high-quality studies encompassing 660 patients with LSCC and 212 controls were included. Several miRNAs were consistently identified across these studies. miR-21-5p was upregulated in four studies and associated with advanced disease stages, lymph node metastasis, and decreased survival rates. miR-125b-5p and miR-126-3p were consistently downregulated, linked to advanced clinical stages and poor tumor differentiation. miR-27a-3p was upregulated in two studies and correlated with poor prognosis, promoting LSCC progression by targeting Smad4. Additionally, miR-33a-5p was identified as a potential diagnostic biomarker with high sensitivity and specificity. These miRNAs show potential as non-invasive biomarkers for the diagnosis and prognosis of LSCC. Conclusions: This systematic review highlights specific circulating miRNAs—particularly miR-21-5p, miR-125b-5p, miR-126-3p, miR-27a-3p, and miR-33a-5p—as promising biomarkers for LSCC. The consistent findings across independent studies emphasize their potential clinical utility in early detection, prognostic assessment, and therapeutic targeting. However, further validation in larger and more diverse populations, along with the standardization of detection methods, is necessary before these biomarkers can be implemented in clinical practice.

The relationship between depth of invasion and cervical lymph node metastasis in patients with laryngeal squamous cell carcinoma.

This study aimed to investigate the relationship between DOI (Depth of Invasion) and metastasis to the neck lymph nodes in patients with laryngeal squamous cell carcinoma (LSCC). This cross-sectional observational study was conducted on all patients diagnosed with LSCC who underwent total laryngectomy and neck dissection between 2014 and 2021. DOI was measured in millimeters by a pathologist who examined the patients' specimens. Demographic information and tumor characteristics were collected and analyzed. The study included 62 patients with LSCC, of whom 23 (37%) had cervical lymph node metastasis. There were 54 (87%) male. The mean DOI was (9.91 ± 1.60) mm in the metastatic group and (7.56 ± 1.42) mm in the non-metastatic group. The results showed that tumors with a higher DOI had a higher probability of cervical lymph node metastasis ( p < 0.001), but there was no significant correlation between DOI and the number of involved lymph nodes (p = 0.318). The analysis also revealed that poorly differentiated tumors (p. value < 0.001), male patients (p. value < 0.001), and older patients (p. value < 0.001) had a higher DOI. According to our results, DOI can be an important predictive factor in predicting cervical lymph node metastasis in LSCC. Therefore, measuring DOI can assist surgeons in decision-making for neck dissection. It is recommended that DOI be determined during surgery using frozen sections or pre-operatively with deep biopsy samples. Considering that laryngeal cancer with cervical lymph node metastasis has a worse prognosis, it could be concluded that greater DOI predicts worse prognosis.

STAT3 Expression in Organ-Preserved Laryngeal Carcinomas: Correlation with Treatment Resistance and Conventional Parameters.

One of the major challenges in the treatment of laryngeal squamous cell carcinoma (LSCC) with organ-preserving therapies is the emergence of treatment resistance. The JAK/STAT pathway has been increasingly implicated in this resistance, particularly through the overexpression or persistent activation of STAT3. Increased STAT3 expression is thought to be associated with resistance to radiotherapy and/or chemotherapy, and STAT3 inhibitors have been proposed as potential targeted treatments. The primary objective of this study is to investigate the relationship between STAT3 expression and treatment resistance in patients with LSCC undergoing organ-preserving therapy and to evaluate the association between STAT3 expression and clinical/histopathologic prognostic parameters. A secondary objective is to evaluate STAT3 expression in diagnostic biopsies and laryngectomy specimens from treatment-resistant patients to investigate the potential predictability of treatment resistance from initial biopsy specimens. The study included 123 patients diagnosed with LSCC between 2008 and 2022, all of whom received nonsurgical treatment. Patients were divided into two groups based on their response to treatment: treatment-sensitive patient group (TSPG) and treatment-resistant patient group (TRPG). Immunohistochemical staining for p-STAT3 was performed on a diagnostic biopsy for each TSPG patient and on both pre- and post-treatment biopsies for each TRPG patient. STAT3 expression levels were scored and their association with treatment resistance, clinical and pathological parameters was analysed. No statistically significant difference in p-STAT3 expression was found between the two groups. TSPG patients were significantly older at diagnosis (p = 0.038), and tumor location differed between groups (p = 0.001). No significant differences in histopathologic or clinical prognostic parameters were observed between patients with high and low STAT3 expression. In addition, no significant difference in STAT3 staining was found between diagnostic biopsies and laryngectomy specimens in TRPG patients. STAT3 expression was not associated with treatment resistance in LSCC, and its expression level did not correlate with prognostic parameters or survival outcomes. Therefore, STAT3 does not appear to be a useful biomarker for predicting treatment resistance or prognosis in LSCC.

Sentinel Node Biopsy in Laryngeal Cancer: A Systematic Review and Meta-Analysis

Background: Sentinel lymph node (SLN) biopsy offers a minimally invasive approach to staging lymph node involvement in laryngeal squamous cell carcinoma (SCC). Despite its adoption in other cancers, its accuracy in laryngeal SCC remains under investigation. This systematic review and meta-analysis evaluates the diagnostic performance of SLN mapping in laryngeal cancer. Methods: A systematic search of MEDLINE, Scopus, and Google Scholar was conducted using the keywords “(larynx OR laryngeal) AND sentinel”, with no date or language restrictions. Studies reporting SLN detection rates and/or sensitivity in laryngeal SCC were included. A random-effects model was applied for data pooling, and subgroup analyses were performed based on tumor location (supraglottic versus transglottic) and mapping material (radiotracer versus blue dye). Publication bias was assessed using funnel plots and statistical methods. Results: Nineteen studies, encompassing 366 patients, were analyzed. The overall pooled SLN detection rate was 90.8% (95% CI: 86–94.1), and sensitivity was 88% (95% CI: 81–94). Supraglottic tumors demonstrated superior outcomes (detection rate: 93.7%, sensitivity: 96%) compared to transglottic tumors (detection rate: 84.7%, sensitivity: 71%). Radiotracers significantly outperformed blue dye, with detection rates of 90.8% versus 81.5% and sensitivities of 88% versus 77%. Conclusions: SLN mapping is a reliable technique for staging laryngeal SCC, particularly for supraglottic tumors, where high detection rates and sensitivity were observed. Radiotracers offer superior performance compared to blue dye, underscoring their clinical value. These findings support the feasibility and accuracy of SLN biopsy in laryngeal cancer, while emphasizing the importance of tumor location and mapping material.

Laryngeal Squamous Cell Carcinoma Incidence and Survival Trends in the United States: A Population-Based Analysis of Two Decades.

Laryngeal cancer has undergone a complex evolution in incidence, management, and standards of care over the past 20 years. Disease-wide demographic and survival risk factors have yet to be elucidated. Examine incidence, management, and survival trends in laryngeal cancer from 2000 to 2019. The Surveillance, Epidemiology, and End Results database was utilized to identify age-adjusted incidence rates (AAIRs) of laryngeal squamous cell carcinoma (LSCCa) from 2000 to 2019. Joinpoint regression was conducted to identify annual percentage changes (APCs). Chi-squared analysis was used to find changes in demographic, clinicopathologic, and treatment changes over the study period. Finally, univariate Kaplan-Meier and COX multivariate regressions were conducted to identify survival differences. There were 46 266 cases of LSCCa identified between 2000 and 2019 with AAIR of 2.7 per 100 000 person-years with APC of -2.6% [95% CI: -2.8% to 2.4%]. These rates have largely been down-trending among demographic substratifications. Age at initial diagnosis has been increasing (64.6 → 66.0, p < 0.001). Higher median household income was associated with lower AAIR (35 000 5.3; > $75 000 2.2) and increased annual percentage decrease (< $35 000, -1.1%*; > $75 000, -3.2%*). There were no other clinically significant differences in demographic and clinicopathologic trends although persistent demographic differences were noted. Late T-stage at diagnosis has increased over the study period (T3, 18% → 23%, p < 0.001). Treatment with primary chemoradiotherapy has increased significantly (20.0% → 27.0%, p < 0.001). On univariate analysis, there were no significant differences in survival; however, on multivariate analysis, there has been a progressive improvement in disease-specific and overall survival over 5-year bins. Late-stage disease had a progressive improvement in survival with each treatment period on both univariate and multivariate analysis. There has been a progressively significant decrease in age-adjusted incidence of LSCCa with increased utilization of primary chemoradiotherapy. When adjusted for associated characteristics, there has been a continuing improvement in survival over the study period, primarily in late-stage disease.

Clinicopathological Significance of Extranodal Extension in Hypopharyngeal and Laryngeal Squamous Cell Carcinoma.

The AJCC cutoff value of 2 mm for the extranodal extension (ENE) distance was determined from an analysis of patients with or without adjuvant therapy. The purpose of this study was to find out the ENE distance that reflects prognosis only in patients with head and neck squamous cell carcinoma (SCC) who received adjuvant therapy. The ENE distance was defined for 109 patients who underwent surgery for SCC of larynx or hypopharynx as a primary tumor. To standardize patient conditions, only 26 patients who received additional postoperative treatment were analyzed. Receiver operating characteristic analysis of the ENE distance for overall survival (OS) and recurrence-free survival (RFS) yielded a cutoff value of 4250 μm. Multivariate analysis showed that the ENE distance was an independent poor prognostic factor for OS and RFS. The optimal ENE distance cutoff for OS and RFS in postoperatively treated patients was 4250 μm.

Clinical and Pathological Staging Discrepancies in Laryngeal Cancer: A Systematic Review

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent and challenging malignancies of the head and neck. Clinical staging (cTNM) plays a pivotal role in therapeutic decision-making. However, current imaging modalities often fall short, resulting in discrepancies between cTNM and pathological staging (pTNM). This systematic review aimed to critically evaluate the existing literature on the concordance between clinical and pathological staging of LSCC, quantifying staging inaccuracies and highlighting the prevalence of both under- and overstaging at diagnosis. Methods: A comprehensive search of the English-language literature was conducted across multiple databases, including PubMed, Embase, Scopus, the Cochrane Library, and Web of Science. Eligibility was limited to retrospective case series and observational studies reporting sufficient data to directly correlate individual patients’ cTNM and pTNM classifications. Results: Thirty-one studies comprising 7939 patients met the inclusion criteria. The overall concordance rate between cT and pT was approximately 86.43%. The concordance rates between cT and pT were 82.41%, 82.03%, 78.14%, and 89.64% for cT1, cT2, cT3, and cT4, respectively. Most discordant cases in cT2 and cT3 involved understaging at clinical diagnosis. Conclusions: The limited accuracy of clinical staging in reflecting the true extent of disease remains a critical challenge in the management of LSCC. The inability of current imaging techniques to reliably detect the subtle invasion of key anatomical structures contributes to both under- and overstaging, with significant clinical implications. For patients undergoing non-surgical organ-preservation strategies, these inaccuracies may adversely affect oncologic outcomes.

THG-1/TSC22D4 promotes interleukin-1 signaling through stabilization of TRAF6 in squamous cell carcinoma.

Malignant neoplasms arise within a region of chronic inflammation caused by tissue injuries. Inflammation is a key factor involved in all aspects of tumorigenesis including initiation, proliferation, invasion, angiogenesis, and metastasis. Interleukin-1 (IL-1) plays critical functions in tumor development with influencing the tumor microenvironment and promoting cancer progression. However, the mechanism of continuous activation of IL-1-mediated inflammatory pathway in tumor has not been fully elucidated. This study provides a novel mechanism of the autocrine activation of IL-1 signaling in squamous cell carcinoma (SCC) through a novel oncoprotein, TSC-22 homologous gene-1 (THG-1, also known as TSD22D4). The RNA sequencing analysis revealed that THG-1 overexpression enhances the transcription of NF-κB targets including IL1A, IL1B, TNFA, and IL8. Furthermore, THG-1 knockdown reduced the responsiveness to IL-1 through suppression of NF-κB nuclear translocation. To elucidate the mechanism, we focused on a THG-1 interacting protein, NRBP1. We found that NRBP1 facilitates the degradation of TRAF6 through its E3 ubiquitin ligase activity. THG-1 bound to NRBP1 and suppressed the degradation of TRAF6. Furthermore, THG-1 knockdown reduced TRAF6 abundance and NF-κB activity in SCC cells. Public database analyses of head and neck SCC revealed that high expression of THG-1 is associated with activation of the IL-1 and TNF pathways, which share TRAF6 in the signal transductions. Finally, THG-1 abundance in laryngeal SCC specimens is elevated in patients with recurrence. These results indicated that THG-1 drives the self-sufficiency of IL-1-mediated inflammatory pathway, which could contribute to the future diagnosis and immune therapy of SCCs. Implications: An oncoprotein THG-1/TSD22D4 activates the IL-1-mediated inflammatory pathway through suppression of TRAF6 degradation, which mediates the continuous inflammation in tumors.

TRIB3 is a biomarker of poor prognosis in laryngeal squamous cell carcinoma and may affect tumor development through PI3K / AKT / mTOR pathway.

TRIB3 has been confirmed to participate in and regulate biological metabolic activities in head and neck tumors such as nasopharyngeal carcinoma and oropharyngeal carcinoma, so the purpose of this study was to explore whether there is a correlation between TRIB3 and Laryngeal Squamous Cell Carcinoma (LSCC) and to preliminarily explore the biological characteristics of TRIB3 in LSCC. TRIB3 expression in the LSCC was analyzed based on The Cancer Genome Atlas (TCGA) database. CCK-8 assay, Colony Formation Assay, wound healing assay, and Transwell assay were performed to investigate the roles of TRIB3 in the proliferation, invasion and metastasis of LSCC. The Protein-Protein Interaction (PPI) network of TRIB3 was analyzed based on the STRING database. Western blotting and qRT-PCR were employed to detect the protein and mRNA expression of TRIB3. TRIB3 over-expressed in the LSCC, which was related to the poor prognosis of LSCC. Patients with methylation related to high TRIB3 expression had a poorer prognosis. Knock-down of TRIB3 expression suppresses the growth, invasion and migration of LSCCs via PI3K / AKT / mTOR. TIME analysis, surface checkpoint analysis, and prediction model indicated that TRIB3 related risk model displayed a poor prognosis. This study investigates the role of TRIB3 in the biological characteristics of LSCC, and preliminarily concludes that TRIB3 may be a potentially promising prognostic biomarker for LSCC. TRIB3 may facilitate the growing, invasive and migrating LSCC, leading to a poor prognosis.

CSPG4 overexpression implicates higher risks of recurrence and tumorigenesis after surgical intervention of vocal fold Leukoplakia.

Vocal fold leukoplakia (VFL), a precancerous lesion of the larynx, is characterized by white plaques on the vocal fold mucous membrane. Currently, there are no reliable biomarkers to predict the recurrence and malignant transformation of VFL. Considering chondroitin sulfate proteoglycan 4 (CSPG4) as a biomarker for malignant tumors such as laryngeal squamous cell carcinoma (LSCC), we conducted this cohort study to evaluate the prognostic influence of CSPG4 expression on VFL patients. This study included 44 patients with surgical intervention of VFL. CSPG4 expression in VFL were observed using immunohistochemistry, and the relationship between the prognosis of VFL patients and CSPG4 expression were investigated using Spearman correlation analysis and multiple Cox regression models. During a median follow-up of 89.3 months, recurrence occurred in 19 postsurgical VFL patients, and malignant transformation occurred in 10 patients. The recurrence and malignant transformation group showed significant differences in the H-SCORE of CSPG4 (P = 0.005 and P = 0.045) compared to the the non-recurrence group and the non-malignant transformation group. And the CSPG4 expression level was positive correlation with recurrence and malignant transformation (0.306 or 0.416, spearman correlation confident). Receiver operating characteristic curve analysis indicated that CSPG4 H-SCORE has predictive value for poor prognosis (areas under the curve, 0.742 and 0.710; cut-off points, 82.5 and 177.5, respectively). Multiple Cox regression analysis revealed a statistically significant effect of lesion size (P = 0.014) and CSPG4 H-SCORE (P = 0.005) on recurrence as well as pathological type (P = 0.001) and CSPG4 H-SCORE stratified by 177.5 (P = 0.039). Our survival data indicated that higher CSPG4 expression was associated with a shorter time of recurrence (P = 0.003) and tumorigenesis (P<0.001). CSPG4 overexpression indicates higher risks and shorter time of postoperative VFL recurrence and tumorigenesis. Detection of CSPG4 expression in VFL may be a novel approach to assess the outcome of VFL patients.

The Role of TRPM2 Channel in Doxorubicin-induced Cell Damage in Laryngeal Squamous Cancer Cells.

Laryngeal squamous cell carcinoma is a common type of head and neck cancer. This study investigated the role of the TRPM2 channel in doxorubicin (DOX)-induced cell damage in human laryngeal squamous cancer cells (Hep-2). Cells were exposed to various DOX concentrations and the appropriate dose was found. Then, TRPM2 antagonist ACA was treated. At the end of the study, cell viability test, Western blot and oxidative stress and inflammatory markers were examined. The results showed that TRPM2 channel expression increased with DOX administration, and DOX incubation in cells caused an increase in ROS, MDA, IL-1β, IL-6, and TNF-α levels, while GSH and GSH-Px levels decreased. Concurrent treatment with ACA attenuated these effects and reduced oxidative stress and inflammation. In addition, DOX-induced apoptosis markers including Casp-3, Casp-8, Casp-9, p53, and Bax were elevated, while Bcl-2 levels were decreased; ACA treatment reversed these changes. The study demonstrated that DOX treatment significantly enhances TRPM2 channel activation and ROS production in Hep-2 cells, thereby initiating apoptotic pathways that lead to cell death. Consequently, targeting the TRPM2 channel may represent a promising therapeutic strategy for treating laryngeal cancer.

Open Partial Horizontal Laryngectomy in the Elderly: Oncological and Functional Outcomes.

The aim of the present study was to investigate the oncological and functional prognostic implication of perioperative risk factors in the elderly patient who underwent open partial horizontal laryngectomy (OPHL). A single institution, retrospective case-cohort study. The present study retrospectively reviewed the clinical charts of a cohort of 100 elderly laryngeal squamous cell carcinoma (LSCC) patients who underwent OPHL at our institution. Oncological and functional results were evaluated through univariate analysis. The overall recurrence rate was 19%. The 2 years overall and disease-specific survivals were 72% and 90%, respectively. No perioperative deaths were reported. A postoperative complication was reported in 20 cases (20%). Fifty-four patients (54%) were decannulated during the hospitalization. A percutaneous endoscopic gastrostomy procedure was performed in 12 patients (12%) due to persistent dysphagia. Twenty-six patients experienced postoperative late sequelae (26%), in terms of postoperative laryngeal obstruction (POLO) in 17 cases. A total of 80 patients (80%) were finally successfully decannulated. A functional total laryngectomy was performed in 6 cases. The indication to OPHL should be carefully evaluated in the elderly. In appropriately selected patient, OPHL represents a safe and effective therapeutic option. Cervical positive nodes and an incomplete resection of the tumor with positive surgical margins remain in such population the main prognostic factors for the oncological outcome, these factors have a negative impact on the functional outcome too, due to the need for adjuvant treatment. Hence, OPHL should be offered as a single-modality treatment especially in the elderly. 4 Laryngoscope, 2025.

Elevated expression of let-7b-3p enhances aggressiveness of larynx squamous cell carcinoma cells

Aims: Larynx squamous cell carcinoma (LSCC) is the second most common head and neck malignancy. While let-7b-3p has been shown to have a role in cancer progression in malignancies, there is no research examining the association between LSCC and let-7b-3p. This study aimed to investigate the expression status of let-7b-3p and the potential roles of this microRNA (miRNA) in LSCC. Methods: Using quantitative real-time polymerase chain reaction (qRT-PCR), we examined the expression status of let-7b3p in 36 LSCC samples and the neighboring normal tissues. Then, the let-7b-3p miRNA mimic was transfected into Hep-2 cells via lipofectamine 2000 reagents. Cell viability was determined using the cell viability detection (CVDK-8) kit, and cell migration was evaluated with the scratch assay. To identify differentially expressed genes (DEGs) in larynx cancer GSE137308 and GSE130605 datasets were downloaded and reanalyzed using Gene Expression Omnibus (GEO2R) tool. Potential target genes of let-7b-3p were investigated in the miRNA target prediction and functional annotation database (miRDB). Shared genes between geo datasets and miRDB results were identified and the relationship between these genes and LSCC was investigated in the literature. Results: We demonstrated that the expression levels of let-7b-3p was significantly upregulated in LSCC tumor tissues in comparison to the corresponding normal tissues. Mimic let-7b-3p transfection enhanced Hep-2 cell proliferation and migration. In vitro and bioinformatics analysis showed that overexpression of let-7b-3p can enhance the larynx cancer cell proliferation and migration through MYBPC1. Conclusion: It was evaluated that let-7b-3p/MYBPC1 axis could potentially affect the LSCC process. Let-7b-3p has the potential to be a biomarker for LSCC, therefore, the let-7b-3p/ MYBPC1/LSCC relationship should be elucidated with new studies.

Evaluation of pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy by narrow band imaging

Objective: To investigate the changes in the narrow band imaging (NBI) phenotypes of oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy, and to explore the clinical value of NBI endoscopy in re-evaluation and follow-up of pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy. Methods: Twenty-nine patients diagnosed with locally advanced pharyngeal or laryngeal squamous cell carcinoma in the First Affiliated Hospital of Xiamen University from November 2021 to January 2024 and receiving 2 cycles of neoadjuvant immunochemotherapy were selected, including 26 males and 3 females, aged 43-80 years. Regular NBI and white light (WL) endoscopy examinations, as well as imaging examinations such as CT scans, were performed. After the neoadjuvant immunochemotherapy, 36 specimens from suspected lesions of the pharynx or the larynx were obtained through surgical resection. The NBI findings of the pharyngeal or laryngeal lesions and their relationships with corresponding pathological and imaging results were analyzed with kappa test, Pearson correlation analysis, McNemar test, and Wilcoxon Signed Rank Test. Results: After neoadjuvant immunochemotherapy, primary lesions showed pathological complete response (pCR) in 9 cases, partial response (PR) in 19 cases, and progressive disease (PD) in one case. The NBI phenotypes of pharyngeal and laryngeal malignant tumors after treatment showed high consistency (kappa=0.818, P<0.01) and significant correlations (r=0.852, P<0.01) with their pathological results. WL endoscopic examinations showed inconsistency (kappa=0.239, P=0.12) with their pathological results. NBI endoscopy was more effective in identifying benign lesions after treatment than WL endoscopy (P=0.031). In cases of both PR and pCR of the primary lesion, there were significant differences in NBI phenotypes before and after neoadjuvant immunochemotherapy (all P<0.05), with phenotypes transitioning to lower malignancy and benign lesions, respectively. Among 19 cases with PR, 16 showed concentric/eccentric regression, and 3 showed multipoint focal regression. NBI endoscopy was more accurate in diagnosing benign or malignant lesions, pCR or PR after treatment compared to CT (all P<0.05). Conclusions: The present NBI microvascular classification of the pharyngeal and laryngeal lesions is still applicable for the diagnosis and evaluation in pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy. The changes in NBI phenotypes and ranges can indicate tumor regression, progression, and recurrence. NBI is more accurate in diagnosing pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy compared to WL endoscopy and imaging examinations such as CT.

LncRNA HOXA10-AS as a novel biomarker and therapeutic target in human cancers.

Long non-coding RNAs (lncRNAs) are crucial regulatory molecules that participate in numerous cellular development processes, and they have gathered much interest recently. HOXA10 antisense RNA (HOXA10-AS, also known as HOXA-AS4) is a novel lncRNA that was identified to be dysregulated in some prevalent malignancies. In this review, the clinical significance of HOXA10-AS for the prognosis of various cancers is analyzed. In addition, the major advances in our understanding of the cellular biological functions and mechanisms of HOXA10-AS in different human cancers are summarized. These cancers include esophageal carcinoma (ESCA), gastric cancer (GC), glioma, laryngeal squamous cell carcinoma (LSCC), acute myeloid leukemia (AML), lung adenocarcinoma (LUAD), nasopharyngeal carcinoma (NPC), oral squamous cell carcinoma (OSCC), and pancreatic cancer. We also note that the aberrant expression of HOXA10-AS promotes malignant progression through various underlying mechanisms. In conclusion, HOXA10-AS is expected to serve as an ideal clinical biomarker and an effective cancer therapy target.

METTL3 mediated WISP1 m6A modification promotes epithelial-mesenchymal transition and tumorigenesis in laryngeal squamous cell carcinoma via m6A reader IGF2BP1.

N6-methyladenosine (m6A), is well known as the most abundant epigenetic modification in messenger RNA, but its influence on laryngeal squamous cell carcinoma (LSCC) remains largely unexplored and poorly understood. This study was designed to explore the effects of m6A on WISP1-mediated epithelial-mesenchymal transition (EMT) and tumorigenesis in LSCC. m6A methylated and expression levels of WISP1 in LSCC tumor tissues and cells were measured by MeRIP-qPCR, qRT-PCR, and western blotting. The regulatory mechanism of m6A modification of WISP1 in LSCC was determined using MeRIP-qPCR, RIP, dual luciferase reporter assay, and RNA stability assay. Cell viability was assessed utilizing MTT method. The invasion and migration ability of LSCC cells were determined by transwell and wound healing method, respectively. Tumor xenograft models were used for the in vivo experiments. The m6A methylation level of WISP1 was significantly enhanced in LSCC patients and LSCC cell lines. Overexpression of the m6A methyltransferase METTL3 significantly upregulated WISP1 expression by promoting its m6A methylation level, whereas METTL3 inhibition exhibited the opposite effect in LSCC cells. Functionally, we found that METTL3 accelerated the viability, invasion, migration, and EMT of LSCC cells by upregulating WISP1. Additionally, overexpression of METTL3 increased WISP1 expression and tumorigenesis were verified in in vivo experiments. Mechanistically, m6A-modified WISP1 was recognized by IGF2BP1, which enhanced the stability of WISP1 mRNA. Our findings indicate that the m6A modification of WISP1 promotes EMT in LSCC by enhancing WISP1 mRNA stability via an IGF2BP1-dependent manner, which may highlight an m6A methylation-based approach for LSCC diagnosis and therapy.

Clinical treatment strategy for pT3N0 laryngeal squamous cell carcinoma

Objective:To investigate optimal treatment strategy for pT3N0 laryngeal squamous cell carcinoma（SCC）. Methods:A retrospective study of 150 patients with pT3N0 laryngeal SCC treated in the First Affiliated Hospital of Chongqing Medical University was performed. The efficacies of partial laryngectomy and total laryngectomy, as well as surgery alone and postoperative radiotherapy were evaluated. The overall survival（OS）, disease specific survival（DSS） and disease-free survival（DFS） were analyzed with statistical package from SPSS. Results:Among the 108 patients with glottic laryngeal SCC, there were no significant differences in OS, DSS and DFS between the partial laryngectomy group and the total laryngectomy group（Log-rank=0.184, 0.010 and 0.051, P>0.05）. Similarly, there were no significant differences in OS, DSS and DFS between the surgery-alone group and postoperative radiotherapy group（Log-rank=0.214, 0.251 and 0.003, P>0.05）. Among the 38 patients with supraglottic laryngeal SCC, the OS in the total laryngectomy group was significantly higher than that in the partial laryngectomy group（Log-rank=7.338, P=0.007）. The DSS and DFS in the total laryngectomy group were higher than in the partial laryngectomy group, but the differences were not statistically significant（Log-rank=0.895 and 1.792; P>0.05）. The DFS in the postoperative radiotherapy group was significantly higher than in the surgery-alone group（Log-rank=7.172, P=0.007）, but there were no significant differences in OS and DSS between these two groups（Log-rank=0.010 and 0.876, P>0.05）. Conclusion:For pT3N0 glottic laryngeal cancer patients, the efficacy of partial laryngectomy is comparable to total laryngectomy, same as surgery alone and postoperative radiotherapy. For pT3N0 supraglottic laryngeal cancer patients, total laryngectomy could improve the overall survival, and postoperative radiotherapy could reduce the recurrence. Prospectively randomized study with large samples is still needed.

Bibliometric analysis of laryngeal cancer treatment literature (2003-2023).

Despite advancements in medical science, the 5-year survival rate for laryngeal squamous cell carcinoma remains low, posing significant challenges in clinical management. This study explores the evolution of key topics and trends in laryngeal cancer research. Bibliometric and knowledge graph analysis are utilized to assess contributions in treating this carcinoma and to forecast emerging research hotspots that may enhance future clinical outcomes. The findings aim to guide researchers by identifying new areas, providing valuable insights and innovative perspectives. Data were extracted from the Web of Science Core Collection database on December 1, 2023. Bibliometric and knowledge mapping analyses were conducted using software tools such as R-Studio 4.1.3, CiteSpace 6.1.R6, VOSviewer 1.6.18, and http://bibliometre.com.(Both CiteSpace 6.1.R6 and VOSviewer 1.6.18 are widely used bibliometric analysis software tools, each with distinct features and applications. CiteSpace primarily focuses on analyzing literature citation relationships and generating knowledge graphs to visualize research hotspots, trends, and knowledge structures. Its data sources include platforms such as Web of Science. While CiteSpace excels in presenting knowledge structures through its advanced visualization capabilities, it is relatively complex to operate and less efficient in processing large-scale datasets. As a result, it is frequently employed in exploring research trends across multiple disciplines. On the other hand, VOSviewer is designed to construct various types of bibliometric networks and is characterized by its intuitive and user-friendly interface. It supports a wide range of data sources and produces visually appealing and clear visualizations, making it particularly suitable for multi-disciplinary bibliometric research. Additionally, VOSviewer provides valuable insights that can inform scientific research decision-making. Overall, the two tools differ in terms of functionality, data sources, visualization effects, and operational complexity, offering researchers complementary options for bibliometric analysis based on their specific needs.) From this database, 800 papers were extracted using specific criteria. After narrowing the scope to English-language publications, this number was reduced to 775. To ensure data quality, conference papers, letters, and editorial materials were excluded, focusing only on original research papers and review articles. The analysis showed that 760 theoretical works and review papers were published in 96 academic journals by 4210 authors from 1148 institutions across 60 countries/regions. The United States emerged as the most significant contributor to laryngeal cancer research. The Croatian Rudjer Boskovic Institute was notable for having the highest publication and citation counts. Among individual researchers, Osmak, M was identified as the most prolific and cited. Predominant international collaborations occurred between European and American countries. The Head and Neck Science Journal was the most frequently co-cited publication. Major research themes encompassed morphological aspects, chemotherapy, and molecular pathway mechanisms in laryngeal cancer treatment. Current research hotspots include disease prognosis, models, clinical trials, tumor recurrence, and surveillance. Notably, targeted therapy and immunotherapy are rapidly advancing fields. There is an urgent need to enhance global scholarly communication as the pursuit of effective laryngeal cancer treatment progresses. Focused research on targeting indicators for this type of cancer remains vital. An impending surge in research is driven by investigations into biomarkers, microenvironmental genetic mechanisms, alternatives to systemic chemotherapy, minimally invasive surgery, and herbal medicine explorations.

RETRACTION: Long Non-Coding RNA LOC554202 Promotes Laryngeal Squamous Cell Carcinoma Progression Through Regulating MiR-31.

S. Yang, J. Wang, W. Ge, and Y. Jiang, "Long Non-Coding RNA LOC554202 Promotes Laryngeal Squamous Cell Carcinoma Progression Through Regulating MiR-31," Journal of Cellular Biochemistry 119, no. 8 (2018): 6953-6960, https://doi.org/10.1002/jcb.26902. The above article, published online on 8 May 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl, and Wiley Periodicals LLC. The expression of concern has been agreed due to third-party concerns related to the data presented in the article. Indicators for cloned image elements and inappropriate undeclared image modification were found in Figure 3D. Furthermore, several statements in the introduction are not sufficiently supported by the cited literature. Finally, the statements in the text referring to Figures 1C and 2C contradict the conclusions supported by the data. Accordingly, the article is retracted as the editors have lost confidence in the data presented.

Epigenetic silencing of JAM3 promotes laryngeal squamous cell carcinoma development by inhibiting the Hippo pathway.

Laryngeal squamous cell carcinoma (LSCC), which represents a significant proportion of head and neck squamous cell carcinoma cases, is often diagnosed at advanced stages, underscoring the urgent need for effective biomarkers and therapeutic targets. Junctional adhesion molecule 3 (JAM3) is implicated in various types of cancer; however, its role in LSCC remains unclear. Therefore, the present study aimed to investigate the epigenetic regulation and tumor‑suppressive functions and mechanisms of JAM3 in LSCC. Bioinformatics analysis and 5‑Aza‑2'‑deoxycytidine treatment, which restored JAM3 expression as confirmed by reverse transcription‑quantitative PCR and western blotting, revealed that aberrant hypermethylation of the JAM3 promoter was associated with reduced JAM3 expression and poorer clinical outcomes in patients with LSCC. In vitro experiments, including Cell Counting Kit 8, colony formation and Transwell assays, demonstrated that JAM3 overexpression inhibited LSCC cell proliferation, migration and invasion. Western blotting and immunofluorescence analysis revealed that the tumor‑suppressive function of JAM3 was mediated through activation of the Hippo pathway. By contrast, both in vitro and in vivo experiments showed that JAM3 knockdown enhanced these oncogenic behaviors by inhibiting the Hippo pathway, suggesting its critical tumor‑suppressive role. In conclusion, the results of the present study indicated that JAM3 may be epigenetically downregulated and could function as a novel tumor suppressor gene through the Hippo pathway in LSCC, offering insights into developing targeted treatments and diagnostics.