B cells in head and neck squamous cell carcinoma: current opinion and novel therapy.

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC.

DACH1 regulates macrophage activation and tumour progression in hypopharyngeal squamous cell carcinoma.

Dachshund family transcription factor 1 (DACH1) has been shown to exhibit a tumour-suppressive role in a number of human cancers. However, the role of DACH1 in hypopharyngeal squamous cell carcinoma (HPSCC) and its function in the tumour microenvironment (TME) are still not clear. Crosstalk between cancer cells and tumour-associated macrophages (TAMs) mediates tumour progression in HPSCC. The expression of DACH1, CD86 and CD163 was detected in 71 matched HPSCC-non-cancerous tissue pairs using quantitative real-time polymerase chain reaction and IHC analysis. Cell proliferation, migration and invasion were monitored by colony formation, Transwell and EdU incorporation assays. ChIP-qPCR and dual-luciferase reporter assays were applied to verify the targeting relationships between DACH1 and IGF-1. Stably transfected HPSCC cells were co-cultured with MΦ macrophages to assess macrophage polarization and secretory signals. DACH1 was decreased in HPSCC tissues and was indicative of a poor prognosis for HPSCC patients. Decreased DACH1 expression in HPSCC was associated with fewer CD86+ TAMs and more CD163+ TAMs. Knockdown of DACH1 inhibited the proliferation, migration and invasion of FaDu cells via Akt/NF-κB/MMP2/9 signalling. Additionally, DACH1 was found to directly bind to the promoter region of IGF-1 to downregulate the secretion of IGF-1, which inhibited TAMs polarization through the IGF-1R/JAK1/STAT3 axis. Furthermore, in nude mice, the effects of DACH1 inhibition on tumour progression and M2-like TAMs polarization were confirmed. These findings suggest that IGF-1 is a critical downstream effector of DACH1 that suppresses cell migration and invasion and inhibits TAMs polarization. DACH1 could be a therapeutic target and prognostic marker for HPSCC.

Cancer-associated fibroblasts secret extracellular vesicles to support cell proliferation and epithelial-mesenchymal transition in laryngeal squamous cell carcinoma.

As the critical components of tumor microenvironment, cancer-associated fibroblasts (CAFs) support the development of various type of cancers, including laryngeal squamous cell carcinoma (LSCC), but the detailed molecular mechanisms by which cancer-associated fibroblasts interact with LSCC cells to facilitate its progression have not been fully uncovered. In the present study, by analyzing the contents from normal fibroblasts (NFs) and cancer-associated fibroblasts-derived extracellular vesicles (EVs) with Real-Time qPCR analysis, we found that the tumor-initiating LncRNA TUC338 was significantly upregulated in the cancer-associated fibroblasts-derived extracellular vesicles, compared to the normal fibroblasts-secreted extracellular vesicles. Further experiments confirmed that cancer-associated fibroblasts-derived extracellular vesicles promoted cell proliferation, colony formation abilities, epithelial-mesenchymal transition (EMT) and tumorigenesis of LSCC cells via delivering LncRNA TUC338. The mechanical experiments verified that LncRNA TUC338 was stabilized by METTL3/YTHDF1-mediated N6-methyladenosine (m6A) modifications, and elevated LncRNA TUC338 sponged miR-8485 to upregulate chromobox homolog 2 (CBX2) in LSCC cells in a competing endogenous RNA mechanisms-dependent manner. Moreover, our rescue experiments evidenced that cancer-associated fibroblasts-derived LncRNA TUC338-containing extracellular vesicles-induced supportive effects in LSCC aggressiveness were all abrogated by overexpressing miR-8485 and silencing CBX2. Collectively, this study is the first to identify a novel m6A/LncRNA TUC338/miR-8485/CBX2 axis in CAFs-EVs-mediated LSCC development, and to show its potential as a diagnostic biomarker for LSCC.

A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA.

BACKGROUND: Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. METHODS: We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT-PCR) of 60 paired samples. The tyrosine-tRNA derivative tRFTyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRFTyr in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRFTyr in LSCC. RESULTS: tRFTyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRFTyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRFTyr could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells. CONCLUSIONS: Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRFTyr in LSCC. tRFTyr could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC.

ALKBH5-mediated m6A modification of lncRNA KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9.

It has been shown that N6-methyladenosine (m6A) modification is involved in the development of complex human diseases, especially in the development of cancer. Our research investigated the role and mechanism of the m6A modification of lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) in Laryngeal squamous cell carcinoma (LSCC) progression. Microarray analysis was used to quantitatively detect the m6A apparent transcriptional modification level of lncRNA in LSCC tissue. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), in situ hybridization (ISH) and quantitative real-time PCR (qRT-PCR) were used to examine the m6A modification and expression of KCNQ1OT1. In addition, in vivo and in vitro experiments have tested the effects of KCNQ1OT1 knockdown on the proliferation, invasion and metastasis of LSCC. Mechanically, we found the N6-methyladenosine (m6A) demethylase ALKBH5 mediates KCNQ1OT1 expression via an m6A-YTHDF2-dependent manner and KCNQ1OT1 could directly bind to HOXA9 to further regulate the proliferation, invasion and metastasis of LSCC cells. In general, our research indicates that ALKBH5-mediated m6A modification of KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9.

LncRNA TP73-AS1 promotes nasopharyngeal carcinoma progression through targeting miR-342-3p and M2 polarization via exosomes.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a deadly cancer, mainly presenting in southeast and east Asia. Long noncoding RNAs (lncRNAs) play essential roles in cancer progression. Exosomes are critical for intercellular communication. Thus, the aim of this study was to identify the functional lncRNAs in NPC and its relevant mechanisms. METHODS: Data from public databases were utilized to screen for functional lncRNAs in NPC. Functional and mechanical experiments were performed to determine the role of lncRNAs in NPC and its relative molecular mechanisms. Exosomes derived from NPC cells were isolated to determine their function in tumor-associated macrophages. RESULTS: LncRNA TP73-AS1 was increased in NPC cells and tissues and was associated with a poor prognosis. TP73-AS1 overexpression promoted proliferation, colony formation, and DNA synthesis of NPC cells while TP73-AS1 knockdown showed opposite roles. TP73-AS1 could directly bind with miR-342-3p. MiR-342-3p overexpression attenuated the effect of TP73-AS1 in NPC cells. Furthermore, TP73-AS1 was transferred by exosomes to promote M2 polarization of macrophages. Lastly, exosomal TP73-AS1 enhanced the motility and tube formation of macrophages. CONCLUSIONS: Together, this study suggests that TP73-AS1 promotes NPC progression through targeting miR-342-3p and exosome-based communication with macrophages and that TP73-AS1 might be an emerging biomarker for NPC.

Regulation of laryngeal squamous cell cancer progression by the lncRNA RP11-159K7.2/miR-206/DNMT3A axis.

Long non-coding RNAs (lncRNAs), which are longer than 200 nt, have been proved to play a role in promoting or inhibiting cancer progression. The following study investigated the role and underlying mechanisms of lncRNA RP11-159K7.2 in laryngeal squamous cell carcinoma (LSCC) progression. Briefly, in situ hybridization (ISH) and real-time quantitative PCR (RT-qPCR) showed higher expression of RP11-159K7.2 in LSCC tissues and cell lines. Patients with low expression level of RP11-159K7.2 lived longer compared to those with high expression of RP11-159K7.2 (χ2  = 39.111, ***P < 0.001). Multivariate Cox regression analysis suggested that lncRNA RP11-159K7.2 was an independent prognostic factor for LSCC patients (HR = 2.961, ***P < 0.001). Furthermore, to investigate the potential involvement of RP11-159K7.2 in the development of LSCC, we knocked out the expression of endogenous RP11-159K7.2 in TU-212 cells and AMC-HN-8 cells via CRISPR/Cas9 double vector lentiviral system. RP11-159K7.2 knockout decreased LSCC cell growth and invasion both in vitro and in vivo. Mechanically, we found that RP11-159K7.2 could positively regulate the expression of DNMT3A by sponging miR-206. In addition, a feedback loop was also discovered between DNMT3A and miR-206. To sum up, these findings suggest that lncRNA RP11-159K7.2 could be used as a potential biomarker for prognosis and treatment of LSCC.

lncRNA IGKJ2-MALLP2 suppresses LSCC proliferation, migration, invasion, and angiogenesis by sponging miR-1911-3p/p21.

Because advanced laryngeal squamous cell carcinoma (LSCC) is diagnosed as a malignant tumor with a poor prognosis, the associated mechanisms still need to be further investigated. As key players in the development and progression of LSCC, lncRNAs have attracted increasing attention from many researchers. In this study, a novel lncRNA termed IGKJ2-MALLP2 was identified and investigated for its effects on the development of LSCC. IGKJ2-MALLP2 expression was confirmed by RT-qPCR in 78 pairs of tissues and human laryngeal carcinoma cell lines. The results of this study showed that the expression of IGKJ2-MALLP2 was reduced in LSCC tissues and displayed close relationships with tumor stage, lymph node metastasis, and clinical stage. Using a dual-luciferase reporter assay, the ability of miR-1911-3p to bind both IGKJ2-MALLP2 and p21 mRNA was demonstrated. IGKJ2-MALLP2 could upregulate p21 expression by competitively binding miR-1911-3p. Moreover, IGKJ2-MALLP2 effectively hindered the invasion, migration, and proliferation of AMC-HN-8 and TU212 tumor cells. Furthermore, its high expression could hinder the secretion of VEGF-A and suppress angiogenesis. As revealed by the results of in vitro experiments, IGKJ2-MALLP2 overexpression could restrict tumor growth and blood vessel formation in a xenograft model of LSCC. As indicated from the mentioned findings, IGKJ2-MALLP2, which mediates p21 expression by targeting miR-1911-3p, was capable of regulating LSCC progression and could act as an underlying therapeutic candidate to treat LSCC.

LncRNA MSC-AS1 aggravates nasopharyngeal carcinoma progression by targeting miR-524-5p/nuclear receptor subfamily 4 group A member 2 (NR4A2).

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a subtype of head and neck cancer with dismal prognosis and high relapse rate. The role of long non-coding RNAs (lncRNAs) in NPC has become a research hotspot in recent years. This study aimed to interrogate the function and mechanism of lncRNA MSC antisense RNA 1 (MSC-AS1) in NPC. METHODS: MSC-AS1 level in NPC tissues and cells were detected by RT-qPCR. Function of MSC-AS1 in NPC cells was assessed by CCK-8, EdU, TUNEL, caspase-3 activity, and transwell invasion assay. Interaction of microRNA-524-5p (miR-524-5p) with MSC-AS1 and nuclear receptor subfamily 4 group A member 2 (NR4A2) was determined by RIP and luciferase reporter assays. RESULTS: MSC-AS1 was upregulated in NPC tissues and cells. Functional assays indicated that MSC-AS1 exacerbated cell proliferation, hindered apoptosis, and facilitated invasion and epithelial-to-mesenchymal transition (EMT) in NPC. Mechanistically, MSC-AS1 sequestered miR-524-5p to upregulate NR4A2 expression in NPC cells. Finally, NR4A2 was conformed as an oncogene in NPC, and overexpressed NR4A2 could restore MSC-AS1 knockdown-mediated inhibition on NPC progression. CONCLUSIONS: Our study firstly showed that lncRNA MSC-AS1 aggravated NPC progression by sponging miR-524-5p to increase NR4A2 expression, indicating MSC-AS1 as a novel target for the lncRNA-targeted therapy in NPC.

An epidemiological survey of laryngopharyngeal reflux disease at the otorhinolaryngology-head and neck surgery clinics in China.

PURPOSE: Using the Reflux Symptom Index (RSI), this nationwide study aimed to investigate the incidence, diagnostic status, risk factors, and common symptoms of adult laryngopharyngeal reflux disease (LPRD) at otorhinolaryngology-head and neck surgery (OHNS) clinics in China. METHODS: This multicenter cross-sectional survey began at the different institutions ranged from July to October 2017, and the duration was 12 months. A total of 90,440 eligible patients were finally enrolled from 72 medical institutions in China. All these patients completed the questionnaire based on RSI. In this study, LPRD was defined as RSI > 13. RESULTS: There were 9182 with LPRD among the 90,440 eligible participants (10.15%). However, only 1294 had a history of LPRD diagnosis among those with LPRD (14.09%). There were regional differences in the frequency of LPRD (P < 0.001). The proportions of patients with LPRD in males (vs. females), middle- and old-aged patients (vs. young), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking) were significantly higher (all P < 0.001). Middle and old age, current smoking, and drinking history were independent predictors of LPRD (all P < 0.001, OR 1.240, 1.261, and 1.481, respectively). "Sensations of something stuck in throat or a lump in throat", "clearing throat", and "excess throat mucus or postnasal drip" were the most frequent clinical symptoms in patients with LPRD. CONCLUSIONS: LPRD has a high incidence at the OHNS clinics in China. However, the diagnostic status of this disease is not optimistic. Older age, smoking, and drinking history were risk factors for LPRD.

Comprehensive analysis of the whole coding and non-coding RNA transcriptome expression profiles and construction of the circRNA-lncRNA co-regulated ceRNA network in laryngeal squamous cell carcinoma.

Recently, accumulating evidence has demonstrated that non-coding RNAs (ncRNAs) play a vital role in oncogenicity. Nevertheless, the regulatory mechanisms and functions remain poorly understood, especially for lncRNAs and circRNAs. In this study, we simultaneously detected, for the first time, the expression profiles of the whole transcriptome, including miRNA, circRNA and lncRNA + mRNA, in five pairs of laryngeal squamous cell carcinoma (LSCC) and matched non-carcinoma tissues by microarrays. Five miRNAs, four circRNAs, three lncRNAs and five mRNAs that were dysregulated were selected to confirm the verification of the microarray data by quantitative real-time PCR (qRT-PCR) in 20 pairs of LSCC samples. We constructed LSCC-related competing endogenous RNA (ceRNA) networks of lncRNAs and circRNAs (circRNA or lncRNA-miRNA-mRNA) respectively. Functional annotation revealed the lncRNA-mediated ceRNA network were enriched for genes involved in the tumor-associated pathways. Hsa_circ_0033988 with the highest degree in the circRNA-mediated ceRNA network was associated with fatty acid degradation, which was responsible for the depletion of fat in tumor-associated cachexia. Finally, to clarify the ncRNA co-regulation mechanism, we constructed a circRNA-lncRNA co-regulated network by integrating the above two networks and identified 9 modules for further study. A subnetwork of module 2 with the most dysregulated microRNAs was extracted to establish the ncRNA-involved TGF-ß-associated pathway. In conclusion, our findings provide a high-throughput microarray data of the coding and non-coding RNAs and establish the foundation for further functional research on the ceRNA regulatory mechanism of non-coding RNAs in LSCC.

CircRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/IGF-1R axis.

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with laryngeal squamous cell carcinoma (LSCC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for LSCC from the aspect of circRNA-microRNA (miRNA)-mRNA interaction.Methods: We investigated the expression of circRNAs in three paired LSCC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between LSCC tissues and non-cancerous matched tissues, including 527 up-regulated circRNAs and 414 down-regulated circRNAs. We focused on hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2.Results: circRASSF2 was found to be significantly up-regulated in LSCC tissues and LSCC cell lines compared with paired adjacent non-tumorous tissues and normal cells. Moreover, knockdown of circRASSF2 significantly inhibited cell proliferation and migration in vitro, which was blocked by miR-302b-3p inhibitor. Bioinformatics analysis predicted that there is a circRASSF2/miR-302b-3p/ insulin-like growth factor 1 receptor (IGF-1R) axis in LSCC progression. Dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-302b-3p, and IGF-1R. Western blot verified that inhibition of circRASSF2 decreased IGF-1R expression. Furthermore, silencing circRASSF2 suppressed LSCC growth in vivo Importantly, we demonstrated that circRASSF2 was up-regulated in serum exosomes from LSCC patients. Altogether, silencing circRASSF2 suppresses progression of LSCC by interacting with miR-302b-3p and decreasing inhibiting IGF-1R expression.Conclusion: In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via an miR-302b-3p/IGF-1R axis.

Predictive and Diagnostic Value of Fractional Exhaled Nitric Oxide in Patients with Chronic Rhinosinusitis.

BACKGROUND Fractional exhaled nitric oxide (FeNO) participates in the local defense of the upper respiratory tract. Abnormal FeNO level is directly related to the occurrence of nasal diseases. However, the clinical value of FeNO in the upper airway is limited, which greatly impedes the diagnosis and treatment of nasal diseases. Here, we assessed the level of FeNO and evaluated the diagnostic accuracy of FeNO for chronic rhinosinusitis. MATERIAL AND METHODS We enrolled 35 patients with confirmed nasal inflammation and 30 healthy subjects from December 2016 and June 2017. The FeNO level was measured using a fractional exhaled nitric oxide detector. The level of FeNO in patients with different clinicopathological factors was compared. The diagnostic potential of FeNO for chronic rhinosinusitis was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS FeNO level was significantly lower in patients with nasal inflammation than in healthy subjects (P<0.05). For nasal inflammation diagnosis, FeNO had the highest area under the curve (AUC) at 0.760, with a sensitivity of 93.30% and a specificity of 68.60%. FeNO level was significantly downregulated in chronic rhinosinusitis patients relative to chronic rhinitis patients (P<0.05). FeNO had a good ability to discriminate between chronic rhinosinusitis patients and chronic rhinitis patients, with higher AUC, sensitivity, and specificity of 0.760, 93.30%, and 68.60%, respectively. However, FeNO levels were not significantly different between different histological types of chronic rhinosinusitis (P>0.05). CONCLUSIONS Our results show that FeNO is a useful marker for discriminating chronic rhinosinusitis, and has potential to provide valuable information in the early diagnosis of chronic rhinosinusitis.

MicroRNA-101 is a potential prognostic indicator of laryngeal squamous cell carcinoma and modulates CDK8.

BACKGROUND: Various microRNAs (miRNAs) negatively modulate genes that are involved in cellular proliferation, differentiation, invasion, and apoptosis. In many types of cancer, the expression profiles of these miRNAs are altered. Recently, miR-101 was identified as a tumour suppressor and was found to be expressed at low levels in various types of tumours, including prostate, breast, endometrium, and bladder cancers. However, the function(s) of miR-101 in laryngeal carcinoma remain unknown. METHODS: The expression levels of miR-101 in laryngeal squamous cell carcinoma (LSCC) tissues and cells were detected by qPCR. Cell proliferation, migration, cell cycle, and apoptosis assay were applied to assess the function(s) of miR-101 in vitro. Nude mice subcutaneous tumour model was used to perform in vivo study. Moreover, we identified Cyclin-dependent kinase 8 (CDK8) as the target of miR-101 by a luciferase assay. The possible downstream effectors of CDK8 were investigated in Wnt/ß-catenin signaling pathway. Changes of CDK8, ß-catenin, and cyclin D1 protein levels were analyzed by western blotting and immunohistochemical staining. The prognostic effect of miR-101 was evaluated using the Kaplan-Meier method. RESULTS: Expression of miR-101 was down-regulated in the LSCC tissues compared with the adjacent normal tissues. Furthermore, downregulation of miR-101 correlated with T3-4 tumour grade, lymph node metastasis, and an advanced clinical stage in the LSCC patients examined (P < 0.05). The low level of miR-101 expression was associated with poor prognosis (P < 0.05). CDK8 was identified as the target gene of miR-101 by luciferase reporter assay. Moreover, we showed that up-regulation of miR-101 expression suppressed humen LSCC Hep-2 cells proliferation and migration, and induced cell-cycle arrest. Increased expression of miR-101 induced cells apoptosis both in vitro and in vivo. Correspondingly, exogenous expression of miR-101 significantly reduced the growth of tumour in a LSCC xenograft model. Furthermore, the miR-101 level was inversely correlated with levels of CDK8, ß-catenin, and cyclin D1 in western blotting assay and immunohistochemical staining assay. CONCLUSIONS: These results indicate that miR-101 is a potent tumour repressor that directly represses CDK8 expression. Thus, detection and targeting of miR-101 may represent a novel diagnostic and therapeutic strategy for LSCC patients.

MiR-203 is downregulated in laryngeal squamous cell carcinoma and can suppress proliferation and induce apoptosis of tumours.

MicroRNAs (miRNAs) have been recognised to regulate cancer development and progression in carcinogenesis as either oncogenes or tumour suppressor genes. However, whether miR-203 plays a crucial role in human laryngeal squamous cell carcinoma (LSCC) remains largely unclear. In the study, we have found that miR-203 expression was significantly lower in LSCC tissues than that in corresponding adjacent non-neoplastic tissues and was negatively correlated with ASAP1 expression level. Lower expression of miR-203 was significantly related to poor differentiation, advanced clinical stages, T3-4 tumour grade, lymph node metastasis and decreased 5-year overall survival. Transfection with miR-203 inhibited proliferation, reduced invasion, induced apoptosis and caused G1 phase cell cycle arrest of Hep-2 cells in vitro, suggesting that miR-203 functioned as a tumour suppressor. We have also tested that over-expression of miR-203 may both suppress the growth of xenograft tumours in mice and downregulate the expressions of ASAP1 in vivo. Furthermore, miR-203 may regulate the expressions of mesenchymal transition (EMT) marker of E-cadherin and cancer stem cells (CSCs) marker of CD44. These findings suggest that miR-203 plays a role as a tumour suppressor in LSCC, likely by regulating ASAP1, probably in relation to EMT and CSCs and may serve as a potential target for therapeutic intervention.

The influence of the 'patient-to-patient model' on swallowing problems in patients with supraglottic laryngeal cancer.

AIMS: To evaluate the patient-to-patient model and swallowing problems in Chinese patients with supraglottic laryngeal cancer (SLC), and to find a solution to help SLC patients with swallowing problems. METHODS: Eighty-nine patients who had undergone operation for horizontal partial laryngectomy were chosen and divided randomly into two groups. The European Organization for Research and Treatment of Cancer (EORTC), Swallow Quality-of-Life (SWAL-QOL) and Visual Analogue Scale (VAS) questionnaires were used to measure the quality of life and swallowing situation of those patients. RESULTS: At 0.5 and 1 months after eating, the scores of the EORTC QLQ-C30 and SWAL-QOL of the participant group were significantly higher than those of the nonparticipant group (p < 0.05). One week after eating, the VAS score for swallowing improved significantly from 4.9 to 7.9 in the participant group. However, in the nonparticipant group, the VAS score showed no obvious change (from 4.5 to 4.1). CONCLUSIONS: We concluded that the patient-to-patient model may be utilized in clinical cases to solve swallowing problems of SLC patients, and infered that swallowing problems mainly appeared in 60 to 70-year-olds, and 1 week after eating was a critical time point of communication.

ANXA3-Rich Exosomes Derived from Tumor-Associated Macrophages Regulate Ferroptosis and Lymphatic Metastasis of Laryngeal Squamous Cell Carcinoma.

Tumor-associated macrophages (TAM) induce immunosuppression in laryngeal squamous cell carcinoma (LSCC). The interaction between LSCC cells and TAMs affects the progression of laryngeal cancer through exosomes, but the underlying molecular mechanism remains unclear. Proteomics analysis of TAMs isolated from human laryngeal tumor tissues obtained from patients with confirmed lymphatic metastasis revealed an upregulation of annexin A3 (ANXA3). In TAMs, ANXA3 promoted macrophages to polarize to an M2-like phenotype by activating the AKT-GSK3ß-ß-catenin pathway. In addition, ANXA3-rich exosomes derived from TAMs inhibited ferroptosis in laryngeal cancer cells through an ATF2-CHAC1 axis, and this process was associated with lymphatic metastasis. Mechanistically, ANXA3 in exosomes inhibited the ubiquitination of ATF2, whereas ATF2 acted as a transcription factor to regulate the expression of CHAC1, thus inhibiting ferroptosis in LSCC cells. These data indicate that abnormal ANXA3 expression can drive TAM reprogramming and promote an immunosuppressive microenvironment in LSCC. Meanwhile, ANXA3-rich exosomes inhibit ferroptosis of LSCC cells and promote lymphatic metastasis, thus promoting tumor progression.

Quantitative assessment of the association between GSTM1 null genotype and laryngeal cancer risk.

Previous studies investigating the association between glutathione S-transferase M1 (GSTM1) null genotype and laryngeal cancer risk reported controversial results. Thus, a meta-analysis was performed to clarify the effect of GSTM1 null genotype on laryngeal cancer risk. A literature search was performed for all possible studies. We estimated summary odd ratio (OR) with its 95 % confidence interval (95 % CI) to assess the association. Subgroup analyses were performed by ethnicity or the sample size. 24 individual case-control studies involving a total of 2,809 laryngeal cancer cases and 4,478 controls were finally included into this meta-analysis. Meta-analyses of total 24 studies showed the GSTM1 null genotype was significantly associated with increased laryngeal cancer risk (random-effects OR = 1.44, 95 % CI 1.19-1.73, P < 0.001). Subgroup analyses by ethnicity showed that the GSTM1 null genotype was associated with increased laryngeal cancer risk in both Caucasians (fixed-effects OR = 1.17, 95 % CI 1.04-1.33, P = 0.012) and Asians (random-effects OR = 1.89, 95 % CI 1.28-2.77, P = 0.001). Also, subgroup analyses by sample size also further identified this association above. The cumulative meta-analyses showed a trend of more obvious association between GSTM1 null genotype and increased risk of laryngeal cancer as information accumulated by year. Meta-analysis of available data suggests that GSTM1 null genotype contributes to increased laryngeal cancer risk in both Caucasians and East Asians.

Targeting reactive oxygen species and fat acid oxidation for the modulation of tumor-associated macrophages: a narrative review.

Tumor-associated macrophages (TAMs) are significant immunocytes infiltrating the tumor microenvironment(TME). Recent research has shown that TAMs exhibit diversity in terms of their phenotype, function, time, and spatial distribution, which allows for further classification of TAM subtypes. The metabolic efficiency of fatty acid oxidation (FAO) varies among TAM subtypes. FAO is closely linked to the production of reactive oxygen species (ROS), which play a role in processes such as oxidative stress. Current evidence demonstrates that FAO and ROS can influence TAMs' recruitment, polarization, and phagocytosis ability either individually or in combination, thereby impacting tumor progression. But the specific mechanisms associated with these relationships still require further investigation. We will review the current status of research on the relationship between TAMs and tumor development from three aspects: ROS and TAMs, FAO and TAMs, and the interconnectedness of FAO, ROS, and TAMs.

Silencing SOX11 Alleviates Allergic Rhinitis by Inhibiting Epithelial-Derived Cytokines

Background: Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa affecting the quality of life of patients. SRY-box transcription factor 11 (SOX11) was reported to play important roles in inflammatory responses, but its role in AR is poorly understood. Aims: To explore the role of SOX11 in the development of allergic rhinitis. Study Design: Cell culture and animal study. Methods: An in vivo murine allergic rhinitis model was established using ovalbumin treatment in female mice. Interleukin-13-stimulated human nasal mucosa epithelial cells were used for in vitro studies. Expression levels of SOX11, epithelial-derived cytokines, and mucin were determined in both modesls. Results: SOX11 was highly expressed in allergic rhinitis mice. Allergy symptoms, serum ovalbumin-specific IgE, histamine, eosinophils, goblet cells, and type 2 cytokine secretion were increased in ovalbumin-treated mice. Furthermore, allergic rhinitis mice exhibited overproduction of epithelial-derived cytokines (thymic stromal lymphopoietin, interleukin-25, interleukin-33), C-C motif chemokine ligand 26 (CCL26), and mucin 5 AC (MUC5AC). Silencing SOX11 alleviated the behavioral symptoms and upregulation of epithelial-derived cytokines, CCL26, and MUC5AC. In human nasal mucosa epithelial cells, interleukin-13 enhanced SOX11 expression in a time-dependent manner, and signal transducer and activator of transcription 6 (STAT6) was involved in the interleukin-13-mediated expression of SOX11 by regulating transcription. Knockdown of SOX11 reduced epithelial-derived cytokine expression and MUC5AC levels in interleukin-13-treated human nasal mucosa epithelial cells. Conclusion: SOX11 plays a critical role in allergic rhinitis development by regulating epithelial-derived cytokines and might be a new therapeutic target for allergic rhinitis.