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Conclusion: These results provided a battery of genes relating to TPF chemotherapeutic sensitivity and might act as molecular targets in laryngeal squamous cell carcinoma (LSCC) treatment. Moreover, these candidate biomarkers could contribute to LSCC individualized treatment. Objectives: To screen out a set of candidate genes which could help to determine whether patients with LSCC could benefit from TPF induction chemotherapy. Method: Gene-expression profiles in seven TPF-sensitive patients were compared to four resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line UMSCC5 after TPF treatment were observed by qRT-PCR. Results: Through microarray analysis, 1546 differently expressed genes were identified, of which 769 were up-regulated in TPF chemotherapy-responsive tissues, whereas 777 were down-regulated. Gene ontology (GO) analysis suggested these genes participating in physiological processes including cell differentiation, metabolism, signal transduction, and cellular component organization. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that Wnt and p53 signaling pathways occupied important roles in TPF chemotherapeutic sensitivity. Moreover, in vitro cell culture experiments revealed the expression alternations of Mapk10, Jun, Vegfb, Pik3r5, Pld1, Tek, Itga6 exposed to TPF treatment by qRT-PCR, whilst providing an insight into the mechanism underlying TPF chemother-apeutic response in LSCC. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor superfamily member 13 (TNFSF13) modulates cell proliferation and apoptosis and participates in the pathogenesis of solid tumors, but its role in laryngeal cancer development is not clearly defined. In order to investigate whether TNFSF13 can be used as a biomarker for diagnosis and prognosis in laryngeal squamous cell carcinoma (LSCC) and the role of TNFSF13 in laryngeal cancer carcinogenesis, we conducted immunohistochemistry and ELISA assays to evaluate the expression level of TNFSF13 in laryngeal cancer patients and the contrast. We also conducted experiments on the functional study of TNFSF13 in vitro. We found that the expression levels of TNFSF13, ki-67, and NF-κB p65 in LSCC tumor tissues were higher than those in vocal polyp and para-carcinoma tissues. The Spearman rank correlation analysis showed that the expression of TNFSF13 had a positive correlation with the expression of ki-67 and NF-κB p65. Cox regression analysis and Kaplan-Meier plots confirmed the expression level of TNFSF13 was a prognostic factor for LSCC. Moreover, the serum TNFSF13 level was significantly higher in LSCC patients than in the controls, and the serum expression level of TNFSF13 can distinguish LSCC from healthy people, precancerosis, or laryngeal benign tumor. In addition, functional study of TNFSF13 in vitro revealed that knockdown of TNFSF13 inhibited cell proliferation by inducing G1 phase cell cycle arrest in Hep-2 cells. In conclusion, TNFSF13 may be a potential novel molecular target for diagnosis and prognosis in human LSCC, and therapies that target TNFSF13 may have clinical significance for the treatment of LSCC. [ABSTRACT FROM AUTHOR]

MicroRNAs (MiRNAs) have been recognized to regulate cancer initiation and progression in carcinogenesis as either oncogenes or tumor suppressor genes, but their role in hypopharyngeal cancer development is not clearly defined. To determine whether miRNA-203 can promote tumor growth in human hypopharyngeal squamous cell carcinoma, we conducted experiments on the functional study of miRNA-203 and identification of miRNA-203 regulated target genes in hypopharyngeal cancer cells. We found that cell proliferation and cell colony-forming increased more in the miRNA-203 up-regulated cancer cells than in the negative control cancer cells. Up-regulation of miRNA-203 accelerated cell cycle progression in hypopharyngeal cancer cells. TP63 and B3GNT5 mRNAs were identified and validated as targets of miRNA-203. However, transwell assay and wound scratch assay showed that miRNA-203 did not involve in invasion and metastasis in hypopharyngeal cancer cells. According to the results, we conclude that miRNA-203 can promote tumor growth in human hypopharyngeal squamous cell carcinoma. These results provide the convincing evidence for the first time that up-regulation of miRNA-203 contributes to the malignancy of hypopharyngeal squamous cell carcinoma, possibly through down-regulating TP63 and B3GNT5. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Immune checkpoint inhibitors, such as nivolumab, combined with small molecule antiangiogenic receptor tyrosine kinase inhibitors (TKIs), present a promising strategy for future immunotherapy. However, combination therapy can lead to specific adverse drug reactions (ADRs) in various clinical settings. Current research on the ADRs associated with combination therapy is limited. Our study aims to assess the safety of combination therapy.We extracted ADR reports on combination therapy from the Food and Drug Administration (FDA) Adverse Event Reporting System database, covering the period from the first quarter of 2012 to the third quarter of 2023, and conducted a large‐scale retrospective study. We evaluated ADR risk signals using the reporting odds ratio (ROR) and calculated the Ro/e ratio to compare the differences in the risk of fatal ADRs among various tumour types.We comprehensively reported the occurrence of ADRs in pan‐cancer patients undergoing combination therapy. The combination therapy significantly increased the risk of sensitive skin (ROR: 231.43, 95% CI: 55.01–973.72, P < .05), metastatic renal cell carcinoma (ROR: 220.71, 95% CI: 28.99–1695.41, P < .05) and renal cell carcinoma (ROR: 188.22, 95% CI: 44.24–800.85, P < .05). We also compared the differences in ADRs resulting from different small molecule drug combinations, as well as the differences in ADRs among patients with different types of tumours under combination therapy. Furthermore, we analysed the characteristics of patients prone to experiencing fatal ADRs.These results can help enhance understanding of the ADRs commonly associated with combination therapy and assist oncologists in formulating screening protocols. [ABSTRACT FROM AUTHOR]

Background: Non‑intestinal adenocarcinoma of the nasal cavity and paranasal sinuses (non‑ITAC) is a heterogeneous tumour that has rarely been reported in previous studies. We compared and analysed the symptoms, radiographic and pathological features, treatment methods, and prognosis of patients with low-grade (G1) and high-grade (G3) tumours. Methods: This was a retrospective study included 22 patients with pathologically confirmed non-ITAC of the nasal cavity and paranasal sinuses who were treated between January 2008 and December 2021 at a single centre. Of these, 11 patients had G1 tumours, and 11 patients had G3 tumours. Clinicopathological features, treatment methods, and survival outcomes were analysed. Results: The median follow-up period was 48.5 months. Nasal congestion was the most common initial symptom, and the nasal cavity was the most frequently involved site. For G1 tumours, the main treatment was simple surgery, 1 and 3‑year overall survival (OS) rates were 100 and 88.9%, while the 1 and 3‑year local control (LC) rates were 100 and 100%, respectively. For G3 tumours, the main treatments were surgery combined with radiotherapy and/or chemotherapy,1 and 3‑year OS rates were 72.7 and 72.7%, while the 1 and 3‑year LC rates were 100 and 90.91%, respectively. G3 tumours was associated with significantly shorter overall survival than G1 tumours (P = 0.035). Patients with stage III-IV showed shorter overall survival compared to stage I-II patients (P = 0.035). Conclusions: Non-ITAC of the nasal cavity and paranasal sinuses may frequently occur in the nasal cavity. The main treatment modality is surgery, supplemented by radiotherapy and chemotherapy. Pathological grade and tumour stage were poor prognostic factors for the disease. [ABSTRACT FROM AUTHOR]

It has been demonstrated that PPARG may interact with the PTEN-PI3K/AKT pathway, contributing to its involvement in the chemotherapy treatment of hypopharyngeal squamous cell carcinoma (HSCC). However, the underlying mechanism remains largely unknown. In this study, gene expression profiles of 17 HSCC patients, comprising 8 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP), were collected and analyzed to investigate expression patterns, correlations, influencing factors of the PPARG-PTEN-PI3K/AKT pathway, and its role in regulating chemosensitivity. The results revealed significantly increased expression (p < 0.04) of AKT1, AKT2, AKT3, PIK3CA, PPARG, and PTEN in the CSP group compared to the CNSP group. Specifically, AKT2 exhibited significant overexpression in tumor tissue (p = 0.01), while AKT2, AKT3, PPARG, and PTEN displayed significant increases in normal tissue (p ≤ 0.04). Positive correlations (R ∈ 0.43 , 0.71 , p < 0.014) were observed between PIK3CA, AKT1, AKT2, AKT3, and PTEN, with AKT2, AKT3, and PTEN also showing significant correlations with PPARG (R ∈ 0.35 , 0.47 , p < 0.04). Age, gender, and disease stage had no influence on PPARG, PIK3CA, and PTEN expression, but they may affect AKT expressions. Pathway analysis revealed that PPARG may interact with the PTEN-PI3K/AKT signaling pathway, playing a crucial role in regulating chemosensitivity in the normal tissue microenvironment. Our results suggest that AKT1 and PIK3CA may be associated with chemosensitivity in HSCC tumor cells, while PPARG and PTEN might exhibit a correlation with a specific segment of the PI3K/AKT pathway, potentially influencing chemosensitivity in the normal tissue microenvironment of HSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prognosis and quality of life for primary malignant maxillary sinus tumors. Methods: This was a retrospective analysis. 164 patients diagnosed with primary malignant maxillary sinus tumors between 2005 and 2018 were recruited. Patients were treated according to the pathological type and the lesion range. Prognostic differences of different pathological types, surgical resection methods, repair methods, treatment methods, and different local recurrence sites were analyzed. Survival analysis and prognostic factors analysis were performed. Results: Overall survival (OS) rate was 74.7% at 3 years, 60.5% at 5 years, and 45.8% at 10 years. Disease-free survival (DFS) rate was 67.2% at 3 years, 45.6% at 5 years, and 30.8% at 10 years. There was significant difference in OS rate among different pathological types (χ2 = 14.18, P < 0.05). The order of 5-year OS rate was as follows: malignant transformation of inverted Papilloma (77.7%) > adenoid cystic carcinoma (74.1%) > squamous cell carcinoma (48.4%) > sarcoma (22.1%). The order of disease-free survival was as follows: total maxillary resection > subtotal maxillary resection > endoscopic nasal tumor resection ≥enlarged maxillary resection, the 5-year DFS rate were 68.6%, 53.5%, 46.2%, and 42.9%, respectively. The OS of postoperative radiotherapy was significantly better than that of preoperative radiotherapy (χ2 = 7.16, P < 0.05). There was significant difference in OS between recurrent and non-recurrent patients (χ2 = 68.57, P < 0.05). Conclusions: The pathological type and the timing of radiotherapy are independent prognostic factors for primary malignant tumor of maxillary sinus. In addition, different local surgical resection methods are independent factors affecting the recurrence rate. [ABSTRACT FROM AUTHOR]

LncRNAs are involved in the initiation and progression of cancer. However, the molecular mechanism and diverse clinical prognosis of MIR31HG in head and neck squamous cell carcinoma (HNSCC) are still unclear. Our previous microarray analysis showed that lncRNA MIR31HG interacted with HIF1A may play an oncogenic role in laryngeal squamous cell cancer (LSCC). To determine whether lncRNA MIR31HG served as a poor prognosis factor and targeted HIF1A to facilitate cell proliferation and tumorigenesis in human HNSCC, we found MIR31HG and HIF1A were overexpressed in LSCC, MIR31HG overexpression or co-expression of HIF1A-positive and p21-negative could serve as a poor prognostic factor for LSCC patients. We further confirmed that MIR31HG promoted cell proliferation, cell cycle progression, and inhibited cell apoptosis in vitro and in vivo. The ingenuity pathway analysis and Western blot indicated that MIR31HG regulated cell cycle progression via HIF1A and p21 in HNSCC. The current results provide evidences for the role of MIR31HG in promoting HNSCC progression and identify MIR31HG as a prognostic biomarker and putative therapeutic target in HNSCC. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The five-year survival rate of HNSCC has not improved even with major technological advancements in surgery and chemotherapy. Currently, docetaxel, cisplatin, and 5-fluoruracil (TPF) treatment has been the most popular chemotherapy method for HNSCC; but only a small percentage of HNSCC patients exhibit a good response to TPF treatment. Unfortunately, at present, no reasonably effective prediction model exists to assist clinicians with patient treatment. For this reason, patients have no other alternative but to risk neoadjuvant chemotherapy in order to determine their response to TPF. In this study, we analyzed the gene expression profile in TPF-sensitive and non-sensitive patient samples. We identified a gene expression signature between these two groups. We further chose 10 genes and trained a support vector machine (SVM) model. This model has 88.3% sensitivity and 88.9% specificity to predict the response to TPF treatment in our patients. In addition, four more TPF responsive and four more TPF non-sensitive patient samples were used for further validation. This SVM model has been proven to achieve approximately 75.0% sensitivity and 100% specificity to predict TPF response in new patients. This suggests that our 10-genes SVM prediction model has the potential to assist clinicians to personalize treatment for HNSCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) ranks seventh among malignant tumors worldwide, with an estimated 500,000 new cases annually. Despite the development of early diagnosis technology, there are still 60% of patients already in the middle–late stages when they were first diagnosed with HNSCC. Despite advances in multidisciplinary synthetic therapy, the overall survival rate remains low, with a five-year survival rate of less than 50%. Thus, it is urgently needed to search for novel early diagnosis biomarkers and therapy targets. In this study, we revealed the role of SOX2-OT in HNSCC progression and metastasis by binding with ILF3, which may serve as a therapeutic target and prognostic biomarker to improve the early diagnosis and overall survival of HNSCC. Long non-coding RNA (lncRNA) is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The molecular mechanism of lncRNA SOX2-OT in HNSCC remains unclear. Therefore, we aimed to elucidate the oncogenic role of SOX2-OT in HNSCC. QRT-PCR analysis was performed in 61 pairs of HNSCC cancer tissues, adjacent normal tissues, and 68 plasma samples confirmed that lncRNA SOX2-OT was overexpressed in cancer tissues and plasma samples, which served as a poor prognostic factor for HNSCC. The FISH assay demonstrated that SOX2-OT was localized in the nucleus and cytoplasm of HNSCC cell lines. Further, the cell function assay confirmed that SOX2-OT promoted cell proliferation and metastasis in vitro and in vivo. RNA pulldown and RIP assay results revealed that SOX2-OT bonds with ILF3 in HNSCC, and the rescue assay confirmed that SOX2-OT played an oncogenic role depending on ILF3 protein expression. Ingenuity pathway analysis and Western blotting indicated that SOX2-OT regulated HNSCC progression by promoting STAT3 phosphorylation and modulating the crosstalk between STAT3 and TGF-β signaling. These results reveal evidence for the role of SOX2-OT in HNSCC progression and metastasis by binding to ILF3, which may serve as a therapeutic target and prognostic biomarker in HNSCC. [ABSTRACT FROM AUTHOR]

Objectives: To explore the feasibility of making a submental perforator flap distal to the connecting line between the mastoid and the sternoclavicular joint under the guidance of neck-enhanced CT and repairing the postoperative defect of upper airway malignancy. Materials and methods: This study retrospectively analysed 19 cases of upper airway malignant tumours treated in our department from January 2021 to September 2022, including 17 males and 2 females, aged 43–70 years. Site of lesions: 15 cases were in the laryngopharynx, 2 cases in the nasal cavity and paranasal sinus and 2 cases on the soft palate. All the lesions were malignant and at stages T2–4N0–2M0. Surgical method: The extended submental perforator flap (size 22–15 × 6–7 cm) was prefabricated distal to the connecting line between the mastoid and the sternoclavicular joint. After tumour resection, the flap was used to repair the postoperative defect. Fifteen cases of laryngopharyngeal malignant tumours were repaired using the extended submental perforator flap with the vascular pedicle located on the opposite side of the tumour body. Two cases of nasal cavity and paranasal sinus tumours were repaired using the extended submental perforator flap combined with the temporalis muscle flap. The soft palate was completely removed in two patients with soft palate cancer and repaired using the folded extended submental perforator flap. Results: Before the surgery, the reflux vein was observed by neck-enhanced CT, including 12 cases returning to the internal jugular vein and 7 cases to the external jugular vein. All 19 cases in which flaps were used survived, and 1 case had a postoperative infection. All the patients had nasal feeding removed after surgery. The tracheal cannula was removed from the patients with laryngeal preservation, and the pronunciation was satisfactory. Among them, patients with soft palate cancer repair had mild nasal reflux symptoms with smooth breathing. During the follow-up period of 4–24 months, 18 patients had no tumour recurrence or metastasis, and 1 patient had cervical lymph node metastasis. Conclusions: This study highlights the use of a submental perforator flap distal to the connecting line between the mastoid and the sternoclavicular joint to repair postoperative defects for upper airway malignancy as an innovative surgical approach that provides more tissue and good arteriovenous blood supply to adjacent sites. This method has high clinical value and provides an effective option for repairing postoperative defects of upper airway malignancy. [ABSTRACT FROM AUTHOR]

PPARG has been reported to promote chemosensitivity in hypopharyngeal squamous cell carcinoma (HSCC). However, few studies tested its significance in the texture of a complex molecular network regulating chemosensitivity in HSCC. Here, we first employed RNA expression data analysis and literature data mining to uncover candidate genes related to HSCC chemosensitivity. Then, we constructed the molecular network regulating chemosensitivity in HSCC. After that, we employed degree centrality (DC) and weighted centrality (WC) to test the significance of PPARG within the regulating network. Pathway enrichment was done to study the cofunctions of PPARG and the rest of the genes within the network. The findings of our study contribute to the construction of a comprehensive network that regulates HSCC chemosensitivity, consisting of 57 genes, including PPARG. Notably, within this network, PPARG demonstrates a ranking of #5 and #13 based on DC and WC, respectively. Moreover, PPARG is connected to 29 out of the 57 genes and plays roles in multiple functional groups. These top related genes include AKT1, TP53, PTEN, MAPK1, NOTCH1, BECN1, PTGS2, SPP1, and RAC1. PPARG gets enriched in several key functional groups that have been implicated in the regulation of chemosensitivity, including those associated with the response to nutrients, vitamins, and peptides, the cellular response to chemical stress, and the regulation of hormone secretion and growth. Our results emphasize the involvement of PPARG and its interconnectedness with other genes in the regulation of HSCC chemosensitivity. [ABSTRACT FROM AUTHOR]

Background: Central neck metastasis (CNM) is common in patients with papillary thyroid carcinoma (PTC). However, the prediction of CNM risk remains poorly defined, especially for patients with clinically negative lymph nodes. We developed a preoperative clinical nomogram to predict CNM risk in patients with clinical T1-2N0 (cT1-2N0) PTC. Methods: Data from 436 patients with unifocal cT1-2N0 PTC were available. We analyzed the association between preoperative variables and CNM using univariate and multivariate logistic regression and developed a clinical nomogram based on the multivariate regression model. The nomogram was validated externally using an independent dataset. Results: The CNM rate was 25.5%. Three clinical variables were associated with CNM, including age, gender, and tumor size. We built a CNM nomogram integrating these three variables. It had a poor index of internal discrimination (C-index, 0.655; 95% CI 0.596–0.715) and a poor index of external discrimination (C-index, 0.690; 95% CI 0.611–0.769). Conclusions: We developed a preoperative nomogram to quantify the risk of CNM in unifocal cT1-2N0 PTC patients. However, our data showed that preoperative clinical parameters were not able to accurately predict the likelihood of CNM. Other variables need to be investigated to improve the prediction capability of this nomogram. [ABSTRACT FROM AUTHOR]

• This study uncovers a novel mechanism by which M2 macrophage-derived exosomes facilitate the progression of laryngeal squamous cell carcinoma (LSCC) through the transfer of HOXC13-AS to tumor microenvironment macrophages. • Utilizing a combination of advanced techniques, including transmission electron microscopy and western blot, the research provides evidence that M2- exo -mediated HOXC13-AS significantly enhances LSCC malignancy and immune evasion both in vitro and in vivo. • The findings reveal that silencing HOXC13-AS in M2-exo can effectively suppress LSCC's aggressive behavior and its ability to evade the immune system, offering a potential therapeutic target for LSCC treatment. • The study also demonstrates that M2- exo -mediated HOXC13-AS influences the expression of IGF2BP2, a key regulator of cellular functions and immune escape, highlighting the complexity of tumor-microenvironment interactions in LSCC. • By elucidating the role of exosomal HOXC13-AS in LSCC, this research contributes to the understanding of exosome-mediated intercellular communication in cancer progression and immune modulation. This study investigates the role of M2- exo -mediated HOXC13-AS in laryngeal squamous cell carcinoma (LSCC) by examining its transmission to tumor microenvironment (TME) macrophages. Exosomes from M2 macrophages were isolated and characterized using transmission electron microscopy, nanoparticle tracer analysis and western blot. Expression of HOXC13-AS, miR-485-5p, IGF2BP2, and PD-L1 was analyzed. Different interventions on LSCC cell function and immune escape were detected using molecular biological techniques. The study found that elevated HOXC13-AS were present in LSCC, and M2-exo expression was significantly increased in LSCC cells. Silencing HOXC13-AS in M2-exo inhibited LSCC malignant progression and immune escape in vivo and in vitro. M2- exo -mediated HOXC13-AS also regulated IGF2BP2 expression, impacting cellular biological function and immune escape process. The study concludes that M2- exo -mediated HOXC13-AS promotes LSCC malignancy and immune escape. [ABSTRACT FROM AUTHOR]