Metastasis is a critical determinant for the treatment strategy and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). However, the mechanisms underlying SCCHN ...metastasis are poorly understood. Our study sought to determine the key microRNA and their functional mechanisms involved in SCCHN metastasis. For The Cancer Genome Atlas (TCGA) data analysis, quantitative PCR was used to quantify the level of miR‐30e‐5p in SCCHN and its clinical significance was further analyzed. A series of in vitro and in vivo experiments were applied to determine the effects of miR‐30e‐5p and its target AEG‐1 on SCCHN metastasis. A mechanism investigation further revealed that AEG‐1 was implicated in the angiogenesis and metastasis mediated by miR‐30e‐5p. Overall, our study confirms that miR‐30e‐5p is a valuable predictive biomarker and potential therapeutic target in SCCHN metastasis.
Valuable predictive biomarkerPotential therapeutic targetMetastasis related gene
The canonical Wnt/β‐catenin signalling pathway and autophagy play critical roles in cancer progression. However, the role of Wnt‐mediated autophagy in cancer radioresistance remains unclear. In this ...study, we found that irradiation activated the Wnt/β‐catenin and autophagic signalling pathways in squamous cell carcinoma of the head and neck (SCCHN). Wnt3a is a classical ligand that activated the Wnt/β‐catenin signalling pathway, induced autophagy and decreased the sensitivity of SCCHN to irradiation both in vitro and in vivo. Further mechanistic analysis revealed that Wnt3a promoted SCCHN radioresistance via protective autophagy. Finally, expression of the Wnt3a protein was elevated in both SCCHN tissues and patients' serum. Patients showing high expression of Wnt3a displayed a worse prognosis. Taken together, our study indicates that both the canonical Wnt and autophagic signalling pathways are valuable targets for sensitizing SCCHN to irradiation.
Myeloid cells are a major heterogeneous cell population in the tumor immune microenvironment (TIME). Imbalance of myeloid response remains a major obstacle to a favorable prognosis and successful ...immune therapy. Therefore, we aimed to construct a risk model to evaluate the myeloid contexture, which may facilitate the prediction of prognosis and immune infiltration in patients with head and neck squamous cell carcinoma (HNSCC). In our study, six myeloid signature genes (including
,
,
,
,
and
) analyzed from 52 differentially expressed myeloid signature genes were finally pooled to establish a prognostic risk model, termed as myeloid gene score (MGS) in a training cohort and validated in a test cohort and an independent external cohort. Furthermore, based on the MGS subgroups, we were able to effectively identify patients with a poor prognosis, aggressive clinical parameters, immune cell infiltration status and immunotherapy response. Thus, MGS may serve as an effective prognostic signature and predictive indicator for immunotherapy response in patients with HNSCC.
Alternatively activated macrophages in tumor microenvironment is defined as M2 tumor-associated macrophages (M2 TAMs) that promote cancer progression. However, communicative mechanisms between M2 ...TAMs and cancer cells in squamous cell carcinoma of head and neck (SCCHN) remain largely unknown.
Quantitative real-time PCR, western blotting, enzyme-linked immunosorbent assay and flow cytometry were applied to quantify mRNA and protein expression of genes related to M2 TAMs, epithelial-mesenchymal transition (EMT) and stemness. Wounding-healing and Transwell invasion assays were performed to detect the invasion and migration. Sphere formation assay was used to detect the stemness of SCCHN cells. RNA-sequencing and following bioinformatics analysis were used to determine the alterations of transcriptome.
THP-1 monocytes were successfully polarized into M2-like TAMs, which was manifested by increased mRNA and protein expression of CCL18, IL-10 and CD206. Conditioned medium from M2-like TAMs promoted the migration and invasion of SCCHN cells, which was accompanied by the occurrence of EMT and enhanced stemness. Importantly, CCL18 neutralizing antibody partially abrogated these effects that caused by conditional medium from M2-like TAMs. In addition, recombinant human CCL18 (rhCCL18) correspondingly promoted the malignant biological behaviors of SCCHN in vitro. Finally, RNA-sequencing analysis identified 331 up-regulated and 363 down-regulated genes stimulated by rhCCL18, which were statistically enriched in 10 cancer associated signaling pathways.
These findings indicate that CCL18 derived from M2-like TAMs promotes metastasis via inducing EMT and cancer stemness in SCCHN in vitro.
Background
The aim of this retrospective study was to compare the efficacy of transcervical (TC), endoscope‐assisted transoral (TO), and endoscope‐assisted TC for resection of retrostyloid space ...schwannomas.
Methods
The study included patients who underwent complete resection of schwannomas by only one surgical approach. The data we collected included tumor size, estimated blood loss, postoperative complications, and so on. Statistical analysis was performed using one‐way analysis of variance and Fisher's exact test.
Results
The study collected 85 patients with tumors mostly located at the oropharyngeal level who were followed up 6 months at least. The results showed that endoscope‐assisted TO had certain advantages over others. Additionally, the endoscope‐assisted TO set the lowest incidence of neurological complications.
Conclusion
Our findings demonstrate that for team with rich experience in the skull base surgery, endoscope‐assisted TO is a superior option compared to the other two groups for resection of retrostyloid space schwannomas, with the better preservation of neurological function.
Objectives/Hypothesis
To analyze the clinical features, classification, and treatment of adult nasopharyngolaryngeal hemangioma (ANPLH).
Study Design
Retrospective study.
Methods
From February 2009 ...to May 2020, 101 patients with ANPLH were reviewed and analyzed.
Results
Symptoms of ANPLH were frequently displayed as abnormal pharyngeal sensation and functional defection. According to lesion location, ANPLH was divided into five categories including nasopharyngeal, oropharyngeal, hypopharyngeal, laryngeal, and mixed types. The mixed type constitutes the highest portion, and the nasopharyngeal type is the least in our cohort. Most lesions could resect through natural cavity under endoscopy. Patients with mixed lesions had a higher rate of postoperative recurrence and planned multiple surgeries. Acceptable but not severe intraoperative and postoperative complications occurred in our patient cohort.
Conclusions
Patients with ANPLH are always symptomatic and even functional defective, which can be classified into five categories based on lesion location. For these patients, endoscopic surgery through natural cavity is recommended to remove lesions with fewer complications and favorable clinical outcomes.
Level of Evidence
4 Laryngoscope, 131:2724–2728, 2021
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Currently, therapeutic modalities such as surgery, chemotherapy, radiotherapy, and immunotherapy are being ...used to treat HNSCC. However, the treatment outcomes of most patients are dismal because they are already in middle or advanced stage by the time of diagnosis and poorly responsive to treatments. It is therefore of great interest to clarify mechanisms that contribute to the metastasis of cells to identify possible targets for therapy. In this study, we identified the Na+‐coupled bicarbonate transporter, SLC4A7, play essential roles in the metastasis of HNSCC. Our results showed that the relative expression of SLC4A7 messenger RNA was highly expressed in HNSCCs samples from TCGA, and compared with precancerous cells of human oral mucosa (DOK), SLC4A7 was highly expressed in HNSCC cell lines. In vitro and in vivo experiments showed that dysregulation of SLC4A7 had minor influence on the proliferation of HNSCC but impacted HNSCC's migration and invasion. Meanwhile, SLC4A7 could promote epithelial‐mesenchymal transition (EMT) in HNSCC. RNA‐seq, KEGG pathway enrichment analysis and Western blot further revealed that downregulation of SLC4A7 in HNSCC cells inhibited the PI3K/AKT pathway. These findings were further validated via rescue experiments using a small molecule inhibitor of PI3K/mTOR (GDC‐0980). Our findings suggest that SLC4A7 promotes EMT and metastasis of HNSCC through the PI3K/AKT/mTOR signaling pathway, which may be a valuable predictive biomarker and potential therapeutic target in HNSCC.
Objectives
By comparing the endoscopy‐assisted transoral approach (EATA) with external approaches (EAs) for the resection of parapharyngeal space tumors (PPSTs), we determined whether the EATA has ...advantages in terms of operation time, intraoperative bleeding volume, postoperative hospitalization, drainage volume, and complications. At the same time, we summarized the surgical indications for the EATA.
Methods
Systematic literature retrieval was performed in the PubMed, Web of Science, Embase, CNKI, Wanfang, and CQVIP databases up to February 2020. We calculated the mean difference (MD) with a 95% confidence interval (CI) for continuous outcomes and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. The measured outcomes were operative time, bleeding volume, postoperative hospitalization, drainage volume, and complications.
Results
Seven studies involving 318 patients were eligible. Of these patients, 145 patients underwent EATA and 173 patients underwent EA surgery. All the former tumors were benign and located medial or anteromedial to the carotid sheath except for the unrecorded tumors. Compared with EAs, the EATA significantly shortened the operation time (MD = −5.56 min, 95% CI: −9.58 to −1.55), shrank the bleeding volume (MD = −89.02 ml, 95% CI: −126.16 to −51.88), shortened the postoperative hospitalization (MD = −2.44 days, 95% CI: −3.37 to −1.51), reduced the drainage volume (MD = −32.97 ml, 95% CI: −36.24 to −29.70), and lowered the incidence of complications (OR = 0.30, 95% CI: 0.16 to 0.59).
Conclusion
As for PPSTs, with an appropriate and precise patient selection, the EATA is a safe, effective, minimally invasive, and aesthetic surgical modality. Laryngoscope, 131:2246–2253, 2021
Invasion and metastasis are major contributors to treatment failure in patients with head and neck squamous cell carcinomas (HNSCCs) and microRNAs (miRNAs) are reported to play important roles in ...tumor progression. Our study therefore try to find the crucial miRNAs and reveal their molecular and functional mechanisms involved in migration and invasion of HNSCCs. Through The Cancer Genome Atlas (TCGA) data analysis, we screened out miR-3187-3p and its biological function and specific mechanism were further analyzed. The wound-healing and transwell invasion assay demonstrated that miR-3187-3p promoted the capacity of migration and invasion of HNSCCs in vitro. Luciferase reporter assays showed that PER2 was a direct target of miR-3187-3p, which could reverse the effect of miR-3187-3p in HNSCCs. Furthermore, we found that miR-3187-3p / PER2 axis activated the Wnt / β-catenin signaling pathway in HNSCCs. Altogether, our study indicated that miR-3187-3p enhanced migration and invasion by targeting PER2 in HNSCCs.
Hypoxia is a hallmark of progressive cancer. Hypoxic cancer cells trigger glycolysis in response to a decreased O2 supply to meet metabolic and bioenergetic demands. Meanwhile, these responses to ...hypoxia and alterations of the microenvironment promote cancer cell metastasis by increasing transcription of hypoxia-inducible factor (HIF)-regulated genes. However, the detailed mechanism by which hypoxia regulates cancer cell metastasis and glycolysis remains to be investigated. In the present study, we identified that metadherin (MTDH), a multifaceted oncogene, is involved in the regulation of head and neck squamous cell carcinoma (HNSCC) metastasis and invasion under hypoxic conditions. Furthermore, the study indicated that there is a positive feedback loop between HIF-1α and MTDH in HNSCC cells, and that hypoxia promotes HNSCC cell metastasis and epithelial-mesenchymal transition by mediating the HIF-1α-MTDH loop. These findings implicate HIF-1α-MTDH as a promising target for anticancer drugs in solid tumors, and help to explain the pro-tumorigenic and unfavorable effect of MTDH on HNSCC observed in our previous studies.
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