USP39 Promotes the Viability and Migration of Head and Neck Squamous Cell Carcinoma Cell by Regulating STAT1.

Objective: Ubiquitin-specific peptidase 39 (USP39) plays a carcinogenic role in many cancers, but little research has been conducted examining whether it is involved in head and neck squamous cell carcinoma (HNSCC). Therefore, this study explored the functional role of USP39 in HNSCC. Method: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed proteins (DEPs) between the HNSCC tumor and adjacent healthy tissues. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to assess the functional enrichment of DEPs. Immunohistochemistry was used to detect protein expression. The viability and migration of two HNSCC cell lines, namely CAL27 and SCC25, were detected using the cell counting kit-8 assay and a wound healing assay, respectively. Quantitative real-time PCR was used to detect the expression level of signal transducer and activator of transcription 1 (STAT1) mRNA. Results: LC-MS/MS results identified 590 DEPs between HNSCC and adjacent tissues collected from 4 patients. Through GO and KEGG pathway analyses, 34 different proteins were found to be enriched in the spliceosome pathway. The expression levels of USP39 and STAT1 were significantly higher in HNSCC tumor tissue than in adjacent healthy tissue as assessed by LC-MS/MS analysis, and the increased expression of USP39 and STAT1 protein was confirmed by immunohistochemistry in clinical samples collected from 7 additional patients with HNSCC. Knockdown of USP39 or STAT1 inhibited the viability and migration of CAL27 and SCC25 cells. In addition, USP39 knockdown inhibited the expression of STAT1 mRNA in these cells. Conclusion: Our findings indicated that USP39 knockdown may inhibit HNSCC viability and migration by suppressing STAT1 expression. The results of this study suggest that USP39 may be a potential new target for HNSCC clinical therapy or a new biomarker for HNSCC.

USP7 promotes cardiometabolic disorders and mitochondrial homeostasis dysfunction in diabetic mice via stabilizing PGC1ß.

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and is characterized by left ventricular dysfunction. Currently, there is a lack of effective treatments for DCM. Ubiquitin-specific protease 7 (USP7) plays a key role in various diseases. However, whether USP7 is involved in DCM has not been established. In this study, we demonstrated that USP7 was upregulated in diabetic mouse hearts and NMCMs co-treated with HG+PA or H9c2 cells treated with PA. Abnormalities in diabetic heart morphology and function were reversed by USP7 silencing through conditional gene knockout or chemical inhibition. Proteomic analysis coupled with biochemical validation confirmed that PCG1ß was one of the direct protein substrates of USP7 and aggravated myocardial damage through coactivation of the PPARα signaling pathway. USP7 silencing restored the expression of fatty acid metabolism-related proteins and restored mitochondrial homeostasis by inhibiting mitochondrial fission and promoting fusion events. Similar effects were also observed in vitro. Our data demonstrated that USP7 promoted cardiometabolic metabolism disorders and mitochondrial homeostasis dysfunction via stabilizing PCG1ß and suggested that silencing USP7 may be a therapeutic strategy for DCM.

Magneto-Mechanical Coupling Study of Magnetorheological Elastomer Thin Films for Sensitivity Enhancement.

Magnetorheological elastomer thin films (MREFs) exhibit remarkable deformability and an adjustable modulus under magnetic fields, rendering them promising in fields such as robotics, flexible sensors, and biomedical engineering. Here, we fabricated MREF by introducing magnetostrictive particles (MSPs) and evaluated the magneto-mechanical coupling effect on the enhancement of sensitivity. The saturation magnetization (Ms) in a parallel anisotropic TbDyFe-PDMS MREF was 5.8 emu/g, and the initial tensile modulus was 55% greater than that of an Iso MREF. We propose a nonlinear magnetorheological formula on the magnetostriction effect, incorporating magnetic dipole interactions and the nonlinear prestress of magnetic particles. This formula highlights the complex nonlinear relationship between the external magnetic field (H) and the key parameters that affect the enhanced MR effect of MSPs-MREF, such as saturation magnetization, remanence (Mr), magnetostriction constant (λs) and stress deviator in ferromagnetic particles (Sed) in the magnetic chain structure. Furthermore, we validate the influence of the key parameters of the rectified magnetorheological formula on a nonlinear magneto-mechanical behavior of MSPs-MREF in PDMS-based MSPs-MREF models by using finite-element simulations. Finally, we developed a biosensor based on MSPs-MREF to detect human serum albumin at low concentrations in human urine samples. There is a 4-fold increase in sensitivity, a lower detection of limit (0.442 µg/mL), and a faster response time (15 min) than traditional biosensors, which in the future might provide an effective way of detecting biomolecules of low concentrations.

Endoscopy-Assisted Thyroglossal Duct Cyst Resection: A Scoping Review.

OBJECTIVES: Thyroglossal duct cysts (TGDCs) are a common congenital mass in the cervical region. As the traditional surgical approach for TGDC removal, the Sistrunk procedure, often leaves a visible neck scar, the demand for improved cosmetic outcomes has increased. Emerging endoscopy-assisted approaches offer promise for addressing cosmetic concerns. We conducted a scoping review to evaluate the feasibility and safety of endoscopy-assisted TGDC surgery. DATA SOURCES: PubMed, Embase, and Cochrane databases. METHODS: Electronic databases were searched from their respective inception dates to January 2023. Data on surgical approach, patient demographics, surgical procedure, and postoperative outcomes were extracted and analyzed. The quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. RESULTS: The literature search yielded nine articles published between 2011 and 2022. Overall, 85 patients in these studies successfully underwent endoscopy-assisted TGDC surgery using various approaches, including areolar, axillo-breast, transoral-vestibular, and transoral-sublingual. The operative time varied across the studies, ranging from 50 to 480 min. TGDC sizes ranged from 1 to 3 cm in diameter. Complications, including infection, skin bruising, and dysarthria, were reported in seven patients (8%). No cases of conversion to open surgery or postoperative recurrences were reported. CONCLUSION: Endoscopy-assisted surgery is a potential alternative for patients seeking TGDC resection with satisfactory aesthetic results while ensuring safety. However, existing evidence is insufficient to support the superior effectiveness of endoscopy-assisted TGDC surgery over the traditional Sistrunk procedure. Laryngoscope, 134:3038-3043, 2024.

The effects of semaphorin 3A in bone and cartilage metabolism: fundamental mechanism and clinical potential.

Semaphorin 3A (Sema3A) is a neuroinformatic protein molecule with widespread expression across various tissues and organs. Recent investigations have unveiled its pivotal role in the skeletal system, primarily through its binding interactions with two co-receptors, neuropilin-1 (Nrp-1) and members of the plexin family. Prior research has confirmed the expression of Sema3A and its receptors in both osteocytes and chondrocytes. Beyond its expression patterns, Sema3A plays a multifaceted role in regulating bone and cartilage metabolism via employing diverse signaling pathways. Additionally, it engages in collaborative interactions with the immune and nervous systems, contributing to the pathophysiological processes underlying a spectrum of bone and joint diseases. In this paper, we undertake a comprehensive review of recent research developments in this field. Our objective is to deepen the understanding of Sema3A within the context of skeletal physiology and pathology. Furthermore, we aim to furnish a valuable reference for potential therapeutic interventions in the realm of bone and joint diseases.

A predictive model of immune infiltration and prognosis of head and neck squamous cell carcinoma based on cell adhesion-related genes: including molecular biological validation.

Background: Focal adhesion serves as a bridge between tumour cells and the extracellular matrix (ECM) and has multiple roles in tumour invasion, migration, and therapeutic resistance. However, studies on focal adhesion-related genes (FARGs) in head and neck squamous cell carcinoma (HNSCC) are limited. Methods: Data on HNSCC samples were obtained from The Cancer Genome Atlas and GSE41613 datasets, and 199 FARGs were obtained from the Molecular Signatures database. The integrated datasets' dimensions were reduced by the use of cluster analysis, which was also used to classify patients with HNSCC into subclusters. A FARG signature model was developed and utilized to calculate each patient's risk score using least extreme shrinkage and selection operator regression analysis. The risk score was done to quantify the subgroups of all patients. We evaluated the model's value for prognostic prediction, immune infiltration status, and therapeutic response in HNSCC. Preliminary molecular and biological experiments were performed to verify these results. Results: Two different HNSCC molecular subtypes were identified according to FARGs, and patients with C2 had a shorter overall survival (OS) than those with C1. We constructed an FARG signature comprising nine genes. We constructed a FARG signature consisting of nine genes. Patients with higher risk scores calculated from the FARG signature had a lower OS, and the FARG signature was considered an independent prognostic factor for HNSCC in univariate and multivariate analyses. FARGs are associated with immune cell invasion, gene mutation status, and chemosensitivity. Finally, we observed an abnormal overexpression of MAPK9 in HNSCC tissues, and MAPK9 knockdown greatly impeded the proliferation, migration, and invasion of HNSCC cells. Conclusion: The FARG signature can provide reliable prognostic prediction for patients with HNSCC. Apart from that, the genes in this model were related to immune invasion, gene mutation status, and chemosensitivity, which may provide new ideas for targeted therapies for HNSCC.

H2S-removing UiO-66 MOFs for sensitized antibacterial therapy.

Antibiotic tolerance is implicated in difficult-to-treat infections and the development and spread of antibiotic resistance. The high storage capacities and excellent biocompatibilities of UiO-66-based metal-organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. In view of hydrogen sulfide (H2S) having been associated with the development of intrinsic resistance to antibacterial agents, we designed a strategy to potentiate existing antibiotics by eliminating bacterial endogenous H2S. We efficiently fabricated an antibiotic enhancer Gm@UiO-66-MA to remove bacterial H2S and sensitize an antibacterial by modifying UiO-66-NH2 with maleic anhydride (MA) and then loading it with gentamicin (Gm). UiO-66-MA achieved the removal of bacterial endogenous H2S and the destruction of bacterial biofilm by selectively undergoing Michael addition with H2S. Moreover, Gm@UiO-66-MA further enhanced the susceptibility of tolerant E. coli to Gm after reducing bacterial intracellular H2S levels. An in vivo skin wound healing experiment confirmed that Gm@UiO-66-MA could greatly reduce the risk of bacterial reinfection and accelerate wound healing. Overall, Gm@UiO-66-MA offers a promising antibiotic sensitizer for minimizing bacterial resistance and a therapeutic strategy for tolerant bacteria-related refractory infections.

Effectiveness of the recurrent laryngeal nerve monitoring during endoscopic thyroid surgery: systematic review and meta-analysis.

BACKGROUND: Thyroid disease is a common endocrine disorder, and thyroid surgeries and postoperative complications have increased recently. This study aimed to explore the effectiveness of intraoperative nerve monitoring (IONM) in endoscopic thyroid surgery using subgroup analysis and determine confounding factors. MATERIALS AND METHODS: Two researchers individually searched for relevant studies published till November 2022 in the PubMed, Embase, Web of Science and Cochrane Library databases. Eventually, eight studies met the inclusion criteria. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. The odds ratio or risk difference were calculated using fixed-effects models. The weighted mean difference of continuous variables was calculated. Subgroup analysis was performed according to the disease type. RESULTS: Eight eligible papers included 915 patients and 1242 exposed nerves. The frequencies of transient, permanent and total recurrent laryngeal nerve (RLN) palsy were 2.64, 0.19 and 2.83%, respectively, in the IONM group and 6.15, 0.75 and 6.90%, respectively, in the conventional exposure group. In addition, analysis of the secondary outcome indicators for the average total length of surgery, localisation time of the RLN, recognition rate of the superior laryngeal nerve and length of incision revealed that IONM reduced the localisation time of the RLN and increased the identification rate of the superior laryngeal nerve. Subgroup analysis showed that IONM significantly reduced the incidence of RLN palsy in patients with malignancies. CONCLUSIONS: The use of IONM significantly reduced the incidence of transient RLN palsy during endoscopic thyroid surgery, but it did not significantly reduce the incidence of permanent RLN palsy. However, the reduction in the total RLN palsy was statistically significant. In addition, IONM can effectively reduce the location time of the RLN and increase the recognition rate of the superior laryngeal nerve. Therefore, the application of IONM for malignant tumours is recommended.

Development of a Colloidal Gold Immunochromatographic Strip for Rapid Detection of Cyfra 21-1 in Lymph Node Metastasis of Thyroid Cancer.

Thyroid cancer is the most common endocrine tumor, and the rate of early lymph node metastasis may be as high as 60%. Currently, detection of lymph node metastasis of thyroid cancer during surgery is limited and time-consuming. Elevated levels of Cyfra 21-1, the proteolytic portion of cytokeratin, are associated with the metastasis and progression of thyroid cancer and are an effective biomarker for the prognosis and diagnosis of thyroid cancer. In this study, an immunochromatographic strip test based on colloidal gold nanoparticles was developed to semi-quantitatively detect the levels of Cyfra 21-1 in lymph nodes within 15 min. The standard (calibration) curve equation was Y = 0.003708 × X + 0.1101, and the detection limit was 0.55-1.14 ng mL-1. The strip did not detect other protein markers of epithelial cells at a concentration of 500 ng mL-1, including cytokeratin 8, cytokeratin 18, epithelial membrane antigen, and epidermal surface antigen. The ability of the strip to differentiate positive from negative metastasis in 40 lymph node specimens was 100% concordant with that of immunohistochemical staining for Cyfra 21-1. In an assessment of 20 lymph node specimens that had been determined by postoperative histopathology to be positive for lymph node metastasis and 20 specimens that were negative, the sensitivity and specificity of the strip were 100% and 95%, respectively. The sensitivity of the strip remained stable when stored at room temperature for 6 months. Together, these results indicated that although further testing using a larger sample size will be required, this immunochromatographic strip test may be useful for rapid intraoperative detection of thyroid cancer metastasis to lymph nodes.

Parathyroid Hormone Promotes Human Umbilical Vein Endothelial Cell Migration and Proliferation Through Orai1-Mediated Calcium Signaling.

Parathyroid hormone is the main endocrine regulator of extracellular calcium and phosphorus levels. Secondary hyperparathyroidism-induced endothelial dysfunction may be related to calcium homeostasis disorders. Here, we investigated the effects of parathyroid hormone on human umbilical vein endothelial cells (HUVECs) and characterized the involvement of store-operated Ca2+ entry (SOCE) and the nuclear factor of activated T cells (NFAT) signaling pathway. We used immunoblot experiments to find that parathyroid hormone significantly enhanced the expression of the Orai1 channel, a type of channel mediating SOCE, SOCE activity, and Orai1-mediated proliferation of HUVECs but did not increase Orai2 and Orai3. RNA-seq was utilized to identify 1,655 differentially expressed genes (823 upregulated and 832 downregulated) in parathyroid hormone-treated HUVECs as well as enhanced focal adhesion signaling and expression levels of two key genes, namely, COL1A1 and NFATC1. Increased protein and mRNA expression levels of COL1A1 and NFATC1 were confirmed by immunoblotting and quantitative RT-PCR, respectively. Cytosol and nuclei fractionation experiments and immunofluorescence methods were used to show that parathyroid hormone treatment increased NFATC1 nuclear translocation, which was inhibited by a calcineurin inhibitor (CsA), a selective calmodulin antagonist (W7), an Orai channel inhibitor (BTP2), or Orai1 small interfering RNA (siRNA) transfection. Parathyroid hormone also increased COL1A1 expression, cell migration, and proliferation of HUVECs. The PTH-induced increase in HUVEC migration and proliferation were inhibited by CsA, W7, BTP2, or COL1A1 siRNA transfection. These findings indicated that PTH increased Orai1 expression and Orai1-mediated SOCE, causing the nuclear translocation of NFATC1 to increase COL1A1 expression and COL1A1-mediated HUVEC migration and proliferation. These results suggest potential key therapeutic targets of Orai1 and the downstream calmodulin/calcineurin/NFATC1/COL1A1 signaling pathway in parathyroid hormone-induced endothelial dysfunction and shed light on underlying mechanisms that may be altered to prevent or treat secondary hyperparathyroidism-associated cardiovascular disease.

Tug-of-War between Covalent Binding and Electrostatic Interaction Effectively Killing E. coli without Detectable Resistance.

Antimicrobial resistance in Gram-negative bacteria has become one of the leading causes of morbidity and mortality and a serious worldwide public health concern due to the fact that Gram-negative bacteria have an additional outer membrane protecting them from an unwanted compound invading. It is still very difficult for antimicrobials to reach intracellular targets and very challenging to treat Gram-negative bacteria with the current strategies. Here, we found that (o-(bromomethyl)phenyl)boronic acid was incorporated into poly((2-N,N-diethyl)aminoethyl acrylate) (PDEA), forming a copolymer (poly(o-Bn-DEA)) having both phenylboronic acid (B) and ((2-N,N-diethyl)amino) (DEA) units. Poly(o-Bn-DEA) exhibits very strong intramolecular B-N coordination, which could highly promote the covalent binding of phenylboronic acid with lipopolysaccharide (LPS) on the outer membrane of E. coli and lodge poly(o-Bn-DEA) on the LPS layer on the surface of E. coli. Meanwhile, the strong electrostatic interaction between poly(o-Bn-DEA) and the negatively charged lipid preferred tugging the poly(o-Bn-DEA) into the lipid bilayer of E. coli. The combating interactions between covalent binding and electrostatic interaction form a tug-of-war action, which could trigger the lysis of the outer membrane, thereby killing Gram-negative E. coli effectively without detectable resistance.

[ECMO assisted in the rescue of thyroid tumor pressing the cervical trachea and causing suffocation: a case report].

A 74-year-old woman suffered from asphyxia due to a huge thyroid mass compressing cervical trachea. The patient developed dyspnea, orthopnea, shortness of breath. SpO2 was about 90% under high flow oxygen inhalation. Protuberant mass was seen in the anterior midline of neck. The palpation was hard, the boundary was not clear, and the trachea couldn't be touched. Neck CT showed a huge mass in the thyroid and severe tracheal compression. And electronic laryngoscopy showed paralysis in bilateral vocal cord, which were fixed in the paramedian position. With the further development of the disease, the patient appeared asphyxia and was in critical condition. After multidisciplinary consultation, considering the high risk of direct intubation, ECMO was used to assist and performed "total thyroidectomy + tracheostomy" under general anesthesia. The patient got successful treatment finally.

Effect of TRPM2-Mediated Calcium Signaling on Cell Proliferation and Apoptosis in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of death due to cancer, indicating that finding new therapeutic targets or approaches for ESCC treatment is imperative. Transient Receptor Potential cation channel subfamily M, member 2 (TRPM2) is a calcium-permeable, nonselective cation channel that responds to reactive oxygen species (ROS), which are found in the tumor microenvironment and are important regulators of tumorigenesis, cell proliferation, apoptosis, and the therapeutic response. Here, we used immunohistochemical analysis of tumor tissue derived from patients with ESCC to find that the TRPM2 channel protein expression level was increased in tumor tissue compared with adjacent normal tissue. Intracellular calcium concentration measurements, western blotting, and ROS and cell viability assays were used with a human ESCC cell line (TE-1 cells) to find that TRPM2 participated in the ROS hydrogen peroxide-induced increase in intracellular calcium. This increased calcium inhibited cell proliferation and enhanced apoptosis. Pretreatment of cells with the anticancer agent 5-fluorouracil (5-FU) significantly increased ROS production, which potentiated TRPM2-mediated calcium signaling, decreased cell proliferation, and increased apoptosis in TE-1 cells, suggesting that the therapeutic effect of 5-FU in ESCC cells may be mediated by the TRPM2 channel-mediated calcium influx. These findings offer a potential treatment target and provide mechanistic insight into the therapeutic effects of 5-FU in patients with ESCC.

[The significance of preoperative cervical thoracic enhancement CT and CTA in the selection of different tumor surgical methods at the base of the neck to minimize complications].

Objective:To explore the significance of preoperative cervical thoracic enhancement CT and CTA in the selection of different tumor surgical methods at the base of the neck to minimize complications. Methods:Analysing the clinical data of 51 patients who had cervical root tumor surgery, including 24 benign lesions and 27 malignant tumors. Enhanced CT and/or CTA examinations were used before surgery to understand the relationship between tumors and/ or recurrent or metastatic lesions and the unnamed arteriovenous, internal jugular arteriovenous, clavicular arteriovenous, thyroid neck, and cone arteries of the cervical root. According to the preoperative enhanced CT and/or CTA, the tumor was removed by a simple neck incision approach or an endoscopic assisted neck incision approach or a combined neck and chest approach. Results:The patients were followed up for 6 months to 10 years. All 24 benign lesions were completely removed. Twenty-seven cases of malignant tumors were completely resected, 2 cases were palliative and cytoreductive, and no death occurred during the operation; There were 2 cases of hoarseness in 27 cases of malignant tumors in this group; 1 case of permanent hypoparathyroidism, died of complications 1 year after surgery; 1 case of subclavian artery injury and 1 case of subclavian vein rupture, repaired during operation; 2 cases of chylous leakage were cured after timely negative pressure suction and compression; 1 case of pleural trauma was repaired during the operation; 1 case of brachial plexus nerve and sacral nerve injury. One case had mediastinal infection after median dehiscence of the sternum was cured after 3 months of treatment. Conclusion:For different nature and different types of tumors at the neck-thoracic junction, appropriate surgical approaches should be selected according to preoperative enhanced CT and CTA to fully expose the tumors. While effectively protecting important neurovasculature, timely and effective treatment of intraoperative complications, so that it is feasible to safely remove part of the cervical root tumor.

Role of the AMPK/ACC Signaling Pathway in TRPP2-Mediated Head and Neck Cancer Cell Proliferation.

Transient receptor potential polycystic 2 (TRPP2) exerts vital roles in various types of cancer; however, its underlying mechanisms remain largely unknown. This study is aimed at investigating whether knockdown of TRPP2 affected the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling pathway and the proliferation of HN-4, cell line originating from human oral and hypopharyngeal squamous cell carcinoma. In addition, the interactions among AMPK/ACC, AMPK/protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α) and TRPP2/PERK/eIF2α signaling pathways, and their association with cell proliferation were also explored. The results showed that the relative expression levels of phosphorylated (p)-ACC, p-PERK, and p-eIF2α in HN-4 cells were significantly increased following treatment with 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) and significantly decreased in cells treated with compound C. Therefore, consistent with previous studies, the AMPK/ACC and AMPK/PERK/eIF2α signaling pathways were upregulated and downregulated following treatment with an AMPK agonist and inhibitor, respectively. Furthermore, TRPP2 knockdown decreased p-PERK and p-eIF2α expression levels and increased those of p-AMPK and p-ACC. Additionally, knockdown of TRPP2 increased HN-4 cell proliferation, while treatment with an AMPK inhibitor or agonist increased or inhibited TRPP2-specific siRNA-mediated cell proliferation, respectively. In conclusion, silencing of TRPP2 expression increased HN-4 cell proliferation via inhibiting the PERK/eIF2α signaling pathway, while the AMPK/ACC signaling pathway was possibly activated by a feedback mechanism to reduce enhanced cell proliferation.

Identification of a Recurrence Signature and Validation of Cell Infiltration Level of Thyroid Cancer Microenvironment.

Though many patients with thyroid cancer may be indolent, there are still about 50% lymph node metastases and 20% the recurrence rates. There is still no ideal method to predict its relapse. In this study, we analyzed the gene transcriptome profiles of eight Gene Expression Omnibus (GEO), and next screened 77 commonly differential expressed genes. Next, Least Absolute Shrinkage and Selection Operator (LASSO) regression model was performed and seven genes (i.e., FN1, PKIA, TMEM47, FXYD6, SDC2, CD44, and GGCT) were then identified, which is highly associated with recurrence data from the Cancer Genome Atlas (TCGA) database. These patients were then divided into low and high-risk groups with specific risk-score formula. Univariate and multivariate Cox regression further revealed that the 7-mRNA signature plays a functional causative role independent of clinicopathological characteristics. The 7-mRNA-signature integrated nomogram showed better discrimination, and decision curve analysis demonstrated that it is clinically useful. Besides, patient with lower risk score shows a relatively lower level of activated dendritic cells (DCs), resting DCs, regulatory T cells and γδT cells, and process of DCs apoptotic. In conclusion, our present immune-related classifier could produce a potential tool for predicting early-relapse.

Molecular mechanisms and prognostic markers in head and neck squamous cell carcinoma: a bioinformatic analysis.

The purpose of the present study was to enhance understanding of the molecular mechanisms underpinning head and neck squamous cell carcinoma (HNSCC). Microarray datasets were obtained from the gene expression omnibus database. By a bioinformatics method, 109 differentially expressed genes were identified between the two mRNA datasets, and these genes were classified primarily into biological process, molecular function, or cellular component. In the protein-protein interaction network analysis, top 20 hub genes were identified, and five (SERPINE1, SERPINH1, SPP1, PLAU and MMP1) of them were associated with the prognosis of HNSCC patients. Immunohistochemistry result also showed that the expression of the proteins encoded by these five genes were significantly upregulated in HNSCC, matching the bioinformatics analysis. Moreover, 28 differentially expressed miRNAs were also identified, with miR-196a and miR-1 being most upregulated and downregulated respectively. Our results provide potential biomarkers for HNSCC and may improve understanding of the molecular mechanisms underlying HNSCC.

Identification of susceptibility gene mutations associated with the pathogenesis of familial nonmedullary thyroid cancer.

BACKGROUND: Familial nonmedullary thyroid cancer (FNMTC) accounts for approximately 3%-9% of all thyroid cancers; however, the mechanisms underlying FNMTC remain unclear. Environmental and genetic (especially genetic mutation) factors may play important roles in FNMTC etiology, development, and pathogenesis. METHODS: Three affected members, including two first-degree relatives, and three healthy members of a family with FNMTC were studied. We performed whole-exome and targeted gene sequencing to identify gene mutations that may be associated with FNMTC pathogenesis. The results were analyzed using Exome Aggregation Consortium data and the Genome Aggregation Database and further validated using Sanger sequencing. RESULTS: Of 28 pivotal genes with rare nonsynonymous mutations found, 7 were identified as novel candidate FNMTC pathogenic genes (ANO7, CAV2, KANK1, PIK3CB, PKD1L1, PTPRF, and RHBDD2). Among them, three genes (PIK3CB, CAV2, and KANK1) are reportedly involved in tumorigenesis through the PI3K/Akt signaling pathway. CONCLUSION: We identified seven pathogenic genes in affected members of a family with FNMTC. The PI3K/Akt signaling pathway is thought to be closely related to the development of FNMTC, and three of the susceptibility genes identified herein are associated with this pathway. These findings expand our understanding of FNMTC pathogenesis and underscore PI3K/Akt pathology as a potential therapy target.