An integrated mRNA-lncRNA signature for relapse prediction in laryngeal cancer.

Patients with laryngeal cancer with early relapse usually have a poor prognosis. In this study, we aimed to identify a multi-gene signature to improve the relapse prediction in laryngeal cancer. One microarray data set GSE27020 (training set, N = 109) and one RNA-sequencing data set (validation set, N = 85) were included into the analysis. In the training set, the microarray expression profile was re-annotated into an mRNA-long noncoding RNA (lncRNA) biphasic profile. Then, LASSO Cox regression model identified nine relapse-related RNA (eight mRNA and one lncRNA), and a risk score was calculated for each sample according to the model coefficients. Patients with high-risk showed poorer relapse-free survival than patients with low risk (hazard ratios (HR): 6.189, 95% confidence interval (CI): 3.075-12.460, P < 0.0001). The risk score demonstrated good accuracy in predicting the relapse (area under time-dependent receiver-operating characteristic (AUC): 0.859 at 1 year, 0.822 at 3 years, and 0.815 at 5 years). The results were validated in the validation set (HR: 3.762, 95% CI: 1.594-8.877, P = 0.011; AUC: 0.770 at 1 year, 0.769 at 3 years, and 0.728 at 5 years). The multivariate analysis reached consistent results after adjustment by multiple confounders. When compared with a 27-gene signature, a 2-lncRNA signature, and Tumor-Node-Metastasis stage, the risk score also showed better performance (P < 0.05). In conclusion, we successfully developed a robust mRNA-lncRNA signature that can accurately predict the relapse in laryngeal cancer.

The Role and Mechanism of Long Non-Coding RNA HOTAIR in the Oncogenesis, Diagnosis, and Treatment of Head and Neck Squamous Cell Carcinoma.

The most frequent malignant tumor of the head and neck is head and neck squamous cell carcinoma (HNSCC), which has a high frequency, a poor prognosis in the late stages, and subpar therapeutic results. As a result, early HNSCC diagnosis and treatment are urgently needed; however, there are no good diagnostic biomarkers or efficient therapeutic targets at this time. The long-stranded non-coding RNA HOTAIR may be important in the pathogenesis of cancer, according to recent research. By interactions with DNA, RNA, and proteins, it has been demonstrated that HOTAIR, a >200 nucleotide RNA transcript, plays a role in the biological processes of many types of tumor cells, including proliferation, metastasis, and prognosis of HNSCC. Hence, this review discusses HOTAIR's function and molecular mechanisms in HNSCC.

lncRNA HOXC-AS2 promotes the progression of hypopharyngeal cancer by binding to the P62 protein mediating the autophagy process.

Hypopharyngeal carcinoma is the most malignant type of head and neck squamous cell carcinoma, and lncRNAs play an important role in its formation and progression. However, the related specific mechanisms are rarely studied. lncRNAs closely associated with hypopharyngeal cancer were examined by lncRNA sequencing for in-depth exploration of the relationship between HOXC-AS2 and hypopharyngeal cancer pathogenesis. The mRNA expression of HOXC-AS2 and related genes was measured by qRT-PCR, and the biological function of HOXC-AS2 in hypopharyngeal carcinoma was demonstrated by gain- and loss-of-function experiments. RNA pulldown, RNA immunoprecipitation (RIP) and gene body truncation experiments and transcriptome sequencing were used to investigate the potential mechanism of HOXC-AS2 and its downstream genes, including P62, NF-KB and HMOX1. Finally, the biological function of HOXC-AS2 was confirmed in animal experiments. HOXC-AS2 and P62 expression was significantly upregulated in hypopharyngeal cancer tissues compared with normal hypopharyngeal tissues, while HMOX1 expression was decreased. Functionally, HOXC-AS2 overexpression can promote the viability, proliferation, migration and invasion of hypopharyngeal cancer cells and facilitate hypopharyngeal cancer progression. It was confirmed that HOXC-AS2 can bind to the P62 protein and activate the NF-KB signaling pathway, thereby affecting HMOX1 expression and regulating autophagy in hypopharyngeal cancer cells, ultimately regulating the formation and progression of hypopharyngeal cancer. In conclusion, our findings suggest that HOXC-AS2 regulates the progression of hypopharyngeal cancer by regulating autophagy and is abnormally highly expressed in hypopharyngeal cancer tissues. HOXC-AS2 may become a new target for the diagnosis and treatment of hypopharyngeal cancer.

The Ubiquitin-Proteasome System in Tumor Metabolism.

Metabolic reprogramming, which is considered a hallmark of cancer, can maintain the homeostasis of the tumor environment and promote the proliferation, survival, and metastasis of cancer cells. For instance, increased glucose uptake and high glucose consumption, known as the "Warburg effect," play an essential part in tumor metabolic reprogramming. In addition, fatty acids are harnessed to satisfy the increased requirement for the phospholipid components of biological membranes and energy. Moreover, the anabolism/catabolism of amino acids, such as glutamine, cystine, and serine, provides nitrogen donors for biosynthesis processes, development of the tumor inflammatory environment, and signal transduction. The ubiquitin-proteasome system (UPS) has been widely reported to be involved in various cellular biological activities. A potential role of UPS in the metabolic regulation of tumor cells has also been reported, but the specific regulatory mechanism has not been elucidated. Here, we review the role of ubiquitination and deubiquitination modification on major metabolic enzymes and important signaling pathways in tumor metabolism to inspire new strategies for the clinical treatment of cancer.

Automatic three-dimensional nasal and pharyngeal airway subregions identification via Vision Transformer.

OBJECTIVES: Upper airway assessment requires a fully-automated segmentation system for complete or sub-regional identification. This study aimed to develop a novel Deep Learning (DL) model for accurate segmentation of the upper airway and achieve entire and subregional identification. METHODS: Fifty cone-beam computed tomography (CBCT) scans, including 24,502 slices, were labelled as the ground truth by one orthodontist and two otorhinolaryngologists. A novel model, a lightweight multitask network based on the Swin Transformer and U-Net, was built for automatic segmentation of the entire upper airway and subregions. Segmentation performance was evaluated using Precision, Recall, Dice similarity coefficient (DSC) and Intersection over union (IoU). The clinical implications of the precision errors were quantitatively analysed, and comparisons between the AI model and Dolphin software were conducted. RESULTS: Our model achieved good performance with a precision of 85.88-94.25%, recall of 93.74-98.44%, DSC of 90.95-96.29%, IoU of 83.68-92.85% in the overall and subregions of three-dimensional (3D) upper airway, and a precision of 91.22-97.51%, recall of 90.70-97.62%, DSC of 90.92-97.55%, and IoU of 83.41-95.29% in the subregions of two-dimensional (2D) crosssections. Discrepancies in volume and area caused by precision errors did not affect clinical outcomes. Both our AI model and the Dolphin software provided clinically acceptable consistency for pharyngeal airway assessments. CONCLUSION: The novel DL model not only achieved segmentation of the entire upper airway, including the nasal cavity and subregion identification, but also performed exceptionally well, making it well suited for 3D upper airway assessment from the nasal cavity to the hypopharynx, especially for intricate structures. CLINICAL SIGNIFICANCE: This system provides insights into the aetiology, risk, severity, treatment effect, and prognosis of dentoskeletal deformities and obstructive sleep apnea. It achieves rapid assessment of the entire upper airway and its subregions, making airway management-an integral part of orthodontic treatment, orthognathic surgery, and ENT surgery-easier.

USP14 Positively Modulates Head and Neck Squamous Carcinoma Tumorigenesis and Potentiates Heat Shock Pathway through HSF1 Stabilization.

The ubiquitin-proteasome system is a pivotal intracellular proteolysis process in posttranslational modification. It regulates multiple cellular processes. Deubiquitinating enzymes (DUBs) are a stabilizer in proteins associated with tumor growth and metastasis. However, the link between DUBs and HNSCC remains incompletely understood. In this study, therefore, we identified USP14 as a tumor proliferation enhancer and a substantially hyperactive deubiquitinase in HNSCC samples, implying a poor prognosis prediction. Silencing USP14 in vitro conspicuously inhibited HNSCC cell proliferation and migration. Consistently, defective USP14 in vivo significantly diminished HNSCC tumor growth and lung metastasis compared to the control group. Luciferase assays indicated that HSF1 was downstream from USP14, and an evaluation of the cellular effects of HSF1 overexpression in USP14-dificient mice tumors showed that elevated HSF1 reversed HNSCC growth and metastasis predominantly through the HSF1-HSP pathway. Mechanistically, USP14 encouraged HSF1 expression by deubiquitinating and stabilizing HSF1, which subsequently orchestrated transcriptional activation in HSP60, HSP70, and HSP90, ultimately leading to HNSCC progression and metastasis. Collectively, we uncovered that hyperactive USP14 contributed to HNSCC tumor growth and lung metastasis by reinforcing HSF1-depedent HSP activation, and our findings provided the insight that targeting USP14 could be a promising prognostic and therapeutic strategy for HSNCC.

LncRNA FOXD3-AS1/miR-135a-5p function in nasopharyngeal carcinoma cells.

This research aimed to illustrate the biological function and associated regulatory mechanism of lncRNA FOXD3-AS1 (FOXD3-AS1) in nasopharyngeal carcinoma (NPC). This research initially found that FOXD3-AS1 was obviously upregulated in NPC cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR) detection. Next, the direct target of FOXD3-AS1 was predicted by bioinformatics and further verified by dual-luciferase reporter assay. MiroRNA-135a-5p (miR-135a-5p) was identified as the target gene of FOXD3-AS1 and down-expressed in C666-1 cells compared to NP69. In addition, function assays were conducted in C666-1 cells, including methyl tetrazolium assay, flow cytometry, Caspase3 activity detection, and western blot assay. Our results suggested that miR-135a-5p upregulation inhibited NPC cell growth, enhanced cell apoptosis, promoted Caspase3 activity, increased cleaved-Caspase3, and reduced pro-Caspase3 level. Moreover, we found that FOXD3-AS1 knockdown notably inhibited C666-1 cell proliferation, increased cell apoptosis, enhanced Caspase3 activity, enhanced cleaved-Caspase3 expression, and suppressed pro-Caspase3 level in C666-1 cells. However, these findings were reversed in C666-1 cells by miR-135a-5p mimic co-transfection. To sum up, our data showed that FOXD3-AS1 knockdown regulated cell growth and apoptosis in NCP cells via altering miR-135a-5p expression, suggesting that FOXD3-AS1 might be a therapeutic target for NPC diagnosis and treatment.

Co-Expression Network Analysis Identified LTF in Association with Metastasis Risk and Prognosis in Clear Cell Renal Cell Carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer in adults. The 5-year survival rate of patients with advanced ccRCC is less than 30%. Lack of potential biomarkers for treatment and prognosis is a limitation for early diagnosis and treatment of ccRCC. METHODS: We collected microarray profiles of 39 ccRCC and matched normal samples to identify differential expression genes (DEGs). Then, a weighted gene co-expression network analysis (WGCNA) was constructed to identify gene modules associated with the metastasis in ccRCC. The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (HPA, https://www.proteinatlas.org/) database were used for verification set. Finally, we used biological experiments to preliminary investigate the impact of LTF on the tumor biological behavior of ccRCC, including proliferation, migration, invasion, and apoptosis. RESULTS: A total of 15 genetic modules were identified, and the light-green module is considered the most relevant to tumor metastasis. (P = 0.02, R2 = -0.4). Protein-protein interaction (PPI) network was performed to identify the hub nodes in the light-green module. Finally, combining the results of PPI, WGCNA and DEGs, lactotransferrin (LTF) gene was regarded as "real" hub genes for cancer metastasis risk. LTF was subsequently validated using the TCGA database. Immunohistochemistry confirmed that the expression of LTF in ccRCC tumor tissue was significantly lower than that in normal tissue based on the HPA database. Intriguingly, patients with low expression of LTF had lower survival rates (HR = 0.66, 95% CI: 0.49-0.89, P = 0.0067), the expression level of the sample was negatively correlated with tumor stage (P = 0.0385), and patients with low expression of LTF gene were more likely to have distant metastasis (P = 0.038). Overexpression of LTF inhibited the proliferation, migration, invasion and promoted apoptosis of human ccRCC cells in vitro. CONCLUSION: LTF might be a novel prognostic biomarker for ccRCC.

Prognosis analysis of patients with mental disorders with COVID-19: a single-center retrospective study.

Our study aimed to investigate the factors affecting the prognosis of patients with mental disorders with COVID-19. All patients with mental disorders who were diagnosed with COVID-19 at the intensive care unit of Wuhan Mental Health Center during the period January 3 to March 1, 2020 were selected. The influence of the baseline characteristics, clinical symptoms, laboratory parameters and the types of mental disorders on prognosis were analyzed. According to their final prognosis, the patients were divided into the deceased group (5 patients) and the cured group (25 patients). The mortality rate of patients with dementia was significantly higher than that of patients with other mental disorders (P = 0.001). The levels of certain laboratory parameters in the serum of dementia patients were significantly increased compared with levels in nondementia patients (WBC count: 10.100±6.147 vs. 5.694±3.383, p = 0.029; neutrophil count: 8.504± 5.993 vs. 3.764 ± 2.733, P = 0.008; BUN: 8.300± 4.072 vs. 4.364 ± 1.196, P = 0.001). Our research indicated that the mortality rate of dementia patients with COVID-19 was higher than that of patients with other mental disorders. A focus on the inflammatory response of dementia patients may provide novel ideas for reducing mortality.