Relationship between triglyceride-glucose index baselines and trajectories with incident cardiovascular diseases in the elderly population.

BACKGROUND: The triglyceride-glucose (TyG) index is regarded as a sophisticated surrogate biomarker for insulin resistance, offering a refined means for evaluating cardiovascular diseases (CVDs). However, prospective cohort studies have not simultaneously conducted baseline and multi-timepoint trajectory assessments of the TyG index in relation to CVDs and their subtypes in elderly participants. METHODS: After excluding data deficiencies and conditions that could influence the research outcomes, this study ultimately incorporated a cohort of 20,185 participants, with data chronicles extending from 2016 to 2022. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Latent Class Trajectory Model (LCTM) was used to assess the change trends of the TyG index over multiple time points. Utilizing the Cox proportional-hazards models, we assessed the relationship between the baseline quartiles of the TyG index and various trajectories with CVDs and subtypes. RESULTS: During the mean follow-up time of 4.25 years, 11,099 patients experienced new CVDs in the elderly population. After stratifying by baseline TyG quartiles, the higher TyG level was associated with an increased risk of CVDs; the aHR and 95% CI for the highest quartile group were 1.28 (1.19-1.39). Five trajectory patterns were identified by the LCTM model. The low gradual increase group as the reference, the medium stable group, and the high gradual increase group exhibited an elevated risk of CVDs onset, aHR and 95%CIs were 1.17 (1.10-1.25) and 1.25 (1.15-1.35). Similar results were observed between the trajectories of the TyG index with subtypes of CVDs. CONCLUSION: Participants with high levels of baseline TyG index and medium stable or high gradual increase trajectories were associated with an elevated risk of developing CVDs in elderly populations.

Urine N-terminal pro-B-type natriuretic peptide and plasma proenkephalin are promising biomarkers for early diagnosis of cardiorenal syndrome type 1 in acute decompensated heart failure: a prospective, double-center, observational study in real-world.

BACKGROUND: Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients. METHODS: The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted. RESULTS: We found that pPENK [OR 1.093 (95% CI 1.022-1.169), p = 0.010; AUROC = 0.899 (95% CI 0.831-0.946)] and uNT-proBNP/uCr ratio [OR 1.015 (95% CI 1.003-1.028), p = 0.012; AUROC = 0.934 (95% CI 0.874-0.971)] could independently predict the occurrence of CRS-1 in hospitalized patients with ADHF. The pPENK [HR 1.014 (95% CI 1.000-1.042), p = 0.044] and uNT-proBNP/uCr ration [HR 0.998 (95% CI 0.997-1.000), p = 0.045] were also independent predictors of the risk of HF readmission or all-cause death 90 d after discharge in ADHF patients. CONCLUSIONS: The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients.

miR-34a-5p was involved in chronic intermittent hypoxia-induced autophagy of human coronary artery endothelial cells via Bcl-2/beclin 1 signal transduction pathway.

Autophagy refers to the genetically regulated process to regulate the survival and death of cells, which is conserved in evolution. Typically, autophagy exerts a vital part under physiopathological conditions. Whether autophagy can be resulted from chronic intermittent hypoxia (CIH), a prominent characteristic of obstructive sleep apnea-hypopnea syndrome (OSAHS), remains to be investigated. Furthermore, microRNAs (miRNAs) can serve as the regulating factors in a variety of benign and malignant diseases; nonetheless, it remains to be fully illustrated about the way by which miRNAs modulate autophagy. According to our results, for human coronary artery endothelial cells (HCAECs), CIH increased the expression of autophagy-associated proteins, which depended on the concentration and time; besides, it could promote autophagic vacuole (AV) formation. In addition, CIH could activate beclin 1, which was dependent on dose and time. In HCAECs, microRNA-34a-5p (miR-34a-5p) was overexpressed after exposed to CIH, and its target protein B-cell lymphoma 2 (Bcl-2) was downregulated. Moreover, inhibiting miR-34a-5p increased Bcl-2 and p62 expression, while downregulating beclin 1, Vps34, Atg5, and LC3 levels, implying the role of miR-34a-5p in CIH-induced autophagy. Moreover, exogenous upregulation of Bcl-2 could block miR-34a-5p influence on CIH-induced autophagy through suppressing beclin 1 expression. Additionally, beclin 1 could enhance the autophagy induced by CIH. In conclusion, overexpression of miR-34a-5p activated beclin 1 through Bcl-2 inhibition in CIH and participated in CIH-induced autophagy.

Aberrant methylation and downregulation of ZNF667-AS1 and ZNF667 promote the malignant progression of laryngeal squamous cell carcinoma.

BACKGROUND: Dysregulated long noncoding RNAs (lncRNAs) are involved in the development of tumor. Aberrant methylation is one of the most frequent epigenetic alterations that regulate the expression of genes. The aim of this study was to determine the expression and methylation status of ZNF667-AS1 and ZNF667, elucidate their biological function in the development of LSCC, and identify a cis-regulation of ZNF667-AS1 to ZNF667. METHODS: The expression and methylation status of ZNF667-AS1 and ZNF667 in laryngeal cancer cell lines and LSCC samples were tested respectively. The function of two laryngeal cancer cell lines with overexpression of ZNF667-AS1 or ZNF667 was detected. The regulation between ZNF667-AS1 and ZNF667 was determined. RESULTS: Significant downregulation of ZNF667-AS1 was detected in laryngeal cancer cell lines and LSCC tumor tissues. The reduced expression of ZNF667-AS1 was associated with moderate/poor pathological differentiation of LSCC tumor tissues. Aberrant hypermethylation of the CpG sites of ZNF667-AS1, closing to the transcriptional start site (TSS), was more critical for gene silencing, and associated with moderate/poor pathological differentiation. In vitro hypermethylation of promoter region closing to TSS of ZNF667-AS1 decreased the luciferase reporter activity. Overexpression of ZNF667-AS1 reduced the proliferation, migration, and invasion ability of AMC-HN-8 and TU177 cells. The sense strand, ZNF667, was positively correlated with ZNF667-AS1 in expression and function. Overexpression of ZNF667-AS1 led to increased expression of ZNF667 in mRNA and protein level. ZNF667-AS1 and ZNF667 may be associated with epithelial-mesenchymal transition (EMT) process. CONCLUSIONS: ZNF667-AS1 and ZNF667 are both down-regulated by hypermethylation, and they serve as tumor suppressor genes in LSCC. ZNF667-AS1 regulates the expression of ZNF667 in cis.

Exploring shared pathways and the shared biomarker ERRFI1 in Obstructive sleep apnoea and atherosclerosis using integrated bioinformatics analysis.

Obstructive sleep apnea (OSA) is an upper airway disorder occurring during sleep and is associated with atherosclerosis (AS). AS is a cardiovascular disease caused by environmental and genetic factors, with a high global mortality rate. This study investigated common pathways and potential biomarkers of OSA and AS. Microarray data were downloaded from the Gene Expression Omnibus (GEO) database and used to screen for differentially expressed genes (DEGs) in the OSA and AS datasets. A weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules of OSA and AS. The least absolute shrinkage and selection operators (LASSO) were used to determine critical biomarkers. Immune cell infiltration analysis was used to investigate the correlation between immune cell infiltration and common biomarkers of OSA and AS. Results revealed that differentially expressed genes may be involved in inflammatory processes, chemokine signaling pathways, and molecular changes in cell adhesion. ERBB receptor feedback inhibitor 1 (ERRFI1) was the best-shared biomarker for OSA and AS. Immune infiltration analysis showed that ERRFI1 expression was correlated with immune cell changes. Changes in immune pathways, inflammatory processes, and cell adhesion molecules may underlie the pathogenesis of both diseases, and ERRFI1 may be a potential diagnostic marker for patients with OSA and AS.

Diversity and Biogeography of Human Oral Saliva Microbial Communities Revealed by the Earth Microbiome Project.

The oral cavity is an important window for microbial communication between the environment and the human body. The oral microbiome plays an important role in human health. However, compared to the gut microbiome, the oral microbiome has been poorly explored. Here, we analyzed 404 datasets from human oral saliva samples published by the Earth Microbiome Project (EMP) and compared them with 815 samples from the human gut, nose/pharynx, and skin. The diversity of the human saliva microbiome varied significantly among individuals, and the community compositions were complex and diverse. The saliva microbiome showed the lowest species diversity among the four environment types. Human oral habitats shared a small core bacterial community containing only 14 operational taxonomic units (OTUs) under 5 phyla, which occupied over 75% of the sequence abundance. For the four habitats, the core taxa of the saliva microbiome had the greatest impact on saliva habitats than other habitats and were mostly unique. In addition, the saliva microbiome showed significant differences in the populations of different regions, which may be determined by the living environment and lifestyle/dietary habits. Finally, the correlation analysis showed high similarity between the saliva microbiome and the microbiomes of Aerosol (non-saline) and Surface (non-saline), i.e., two environment types closely related to human, suggesting that contact and shared environment being the driving factors of microbial transmission. Together, these findings expand our understanding of human oral diversity and biogeography.

Correlation of serum nicotinamide phosphoribosyl transferase with hypoxia and Framingham risk score in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for atherosclerosis (AS), but the mechanism is different from classical AS risk factors. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the pathophysiology of AS via multiple pathways, and its expression is closely related to hypoxia. The association of NAMPT with hypoxia and the risk of cardiovascular morbidity in the patients of OSAHS remains to be defined. Therefore, we carried out this study to investigate the association of NAMPT with hypoxia and the risk of early cardiovascular disease [based on the Framingham risk score (FRS)] in patients with OSAHS. METHODS: A total of 82 patients diagnosed with OSAHS were enrolled in this cross-sectional survey design, along with 18 healthy controls who were age- and gender-matched. The general characteristic parameters including height and weight as well as biochemical parameters including blood glucose and lipid were collected from the subjects. The Framingham vascular risk score calculates the risk of developing vascular disease based on the above indicators. Polysomnography was performed in patients with OSAHS, and blood oxygen saturation and apnea-hypopnea index (AHI) were collected, and patients were grouped by disease extent by AHI. The serum NAMPT level of the research subjects was detected using an enzyme-linked immunosorbent assay. Spearman correlation analysis and multiple linear regression to explore the independent correlations of hypoxia on serum NAMPT activity in OSAHS patients. RESULTS: Serum NAMPT level in patients with OSAHS increased with the severity of the disease. Correlation analysis showed that NAMPT was significantly positively correlated with FRS in patients with OSAHS (r=0.829, P<0.05). Multiple linear regression analysis with FRS as the outcome measure showed that NAMPT activity and minimum blood oxygen saturation were independent associated with the risk of developing cardiovascular disease (ß=0.03, P=0.000; ß=-0.13, P=0.034). Univariate and multivariate regression analyses revealed that hypoxia was significantly associated with NAMPT levels in OSAHS patients, and the oxygen desaturation index (ODI) was independent associated with the expression of NAMPT activity (ß=4.09, P=0.000). CONCLUSIONS: In patients with OSAHS, hypoxia is independently associated with NAMPT. NAMPT increases the risk of cardiovascular morbidity in this population may be influenced by hypoxia.

A Prognostic Model of Non-Small Cell Lung Cancer With a Radiomics Nomogram in an Eastern Chinese Population.

Background: The aim of this study was to build and validate a radiomics nomogram by integrating the radiomics features extracted from the CT images and known clinical variables (TNM staging, etc.) to individually predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC). Methods: A total of 1,480 patients with clinical data and pretreatment CT images during January 2013 and May 2018 were enrolled in this study. We randomly assigned the patients into training (N = 1036) and validation cohorts (N = 444). We extracted 1,288 quantitative features from the CT images of each patient. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model was applied in feature selection and radiomics signature building. The radiomics nomogram used for the prognosis prediction was built by combining the radiomics signature and clinical variables that were derived from clinical data. Calibration ability and discrimination ability were analyzed in both training and validation cohorts. Results: Eleven radiomics features were selected by LASSO Cox regression derived from CT images, and the radiomics signature was built in the training cohort. The radiomics signature was significantly associated with NSCLC patients' OS (HR = 3.913, p < 0.01). The radiomics nomogram combining the radiomics signature with six clinical variables (age, sex, chronic obstructive pulmonary disease, T stage, N stage, and M stage) had a better prognostic performance than the clinical nomogram both in the training cohort (C-index, 0.861, 95% CI: 0.843-0.879 vs. C-index, 0.851, 95% CI: 0.832-0.870; p < 0.001) and in the validation cohort (C-index, 0.868, 95% CI: 0.841-0.896 vs. C-index, 0.854, 95% CI: 0.824-0.884; p = 0.002). The calibration curves demonstrated optimal alignment between the prediction and actual observation. Conclusion: The established radiomics nomogram could act as a noninvasive prediction tool for individualized survival prognosis estimation in patients with NSCLC. The radiomics signature derived from CT images may help clinicians in decision-making and hold promise to be adopted in the patient care setting as well as the clinical trial setting.

Expression and regulatory network of miRNAs in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has the sixth-highest incidence rate of all malignant tumors. The occurrence and progress of HNSCC are induced by extensive molecular changes, resulting in a poor prognosis. The present study aims to explore how altered microRNAs (miRNAs) and their co-expression networks of miRNAs-target mRNAs in HNSCC and to provide references for diagnosis and therapy research. METHODS: The reported miRNAs that were ectopically expressed in HNSCC were partly summarized and classified according to the research outcomes. Next, the target mRNAs of miRNAs were predicted using data from online databases. Following that, the co-expression networks between miRNAs and target mRNAs were constructed using Cytoscape. Next, a series of functional enrichment analyses were completed using online databases. RESULTS: A total of 132 miRNAs were summarized using data retrieved from the published literature and then were classified into three grades: A [92], B [18], C [22], according to the research content. Based on these grades, the target mRNAs of the miRNAs in each grade were predicted through data from online databases, and the co-expression networks were constructed separately. Functional enrichment analyses showed that miRNAs participated in multiple molecular functions, biological processes, and signaling pathways. The PI3K-Akt, MAPK, and Wnt signaling pathways, were determined to be regulatory pathways of epithelial-mesenchymal transition (EMT), for instance. CONCLUSIONS: A total of 132 altered miRNAs took part in the regulation of the PI3K-Akt, MAPK, Wnt signaling pathways, and other significant pathways or functions. The present study suggests that miRNAs might be key biomarkers for the diagnosis and therapy of HSNCC.

Clinical significance and potential mechanisms of miR-223-3p and miR-204-5p in squamous cell carcinoma of head and neck: a study based on TCGA and GEO.

OBJECTIVE: To explore the clinical significance and mechanisms of altered miRNAs in squamous cell carcinoma of head and neck (SCCHN) and provide references for SCCHN diagnosis and prognosis. METHOD: Differential expressed miRNAs (DEMs) in SCCHN were screened through gene expression omnibus (GEO) DataSets and verified by the cancer genome atlas (TCGA) database. Next, the overall survival analysis, receiver operating characteristics, and clinical correlation analysis were adopted to filter the miRNAs with diagnostic and prognostic values. Finally, functional enrichment analyses were conducted for inquiring into the mechanisms of miRNAs. RESULTS: Total 103 DEMs (p < 0.05, fold change ≥ 2) in SCCHN were screened out from GSE124566. Partly, the expression levels of the selected (12/17) miRNAs were verified by TCGA. Followed, of the 12 miRNAs, two miRNA expression levels were associated with the overall survival, and five miRNAs showed diagnostic values (AUC ≥ 0.85). Besides, miR-223-3p and miR-204-5p expression levels were correlated to certain clinical features. Epithelial-mesenchymal transition (EMT) related biological process and energy metabolism controlling related AMPK signaling pathway might mediate the roles of miR-223-3p and miR-204-5p, respectively. CONCLUSION: With diagnostic and prognostic values, miR-223-3p and miR-204-5p may be involved in the progression of SCCHN through EMT-related biological process and energy balance related AMPK signaling pathway, respectively.

Aberrant DNA hypermethylation-silenced LINC00886 gene accelerates malignant progression of laryngeal carcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) play crucial role in formation and progression of tumors. DNA methylation has become increasingly recognized as a frequent event of epigenetic alterations and one of the primary mechanisms of gene inactivation. The research aims to investigate the biofunction of a novel lncRNA in LSCC. METHODS: qRT-PCR, BGS, and MSP methods were employed to measure the relative expression level and methylation status of LINC00886. Additionally, we examined the effects of LINC00886 on cells proliferation and invasion using LINC00886 over-expression. Nude mouse xenograft models were conducted to assess LINC00886 effects on LSCC growth in vivo. High-throughput sequencing technology and Western blot assay were carried out to have an in-depth study of the downstream target genes and signaling pathways in which LINC00886 may participate. RESULTS: The remarkable downregulation of LINC00886 was observed in tumor tissues and laryngeal cancer cell lines. The significant decrease of LINC00886 was correlated with pathological grade in LSCC tissues. The expression level of LINC00886 in laryngeal cancer cell lines was significantly reversed by 5-Aza-dC. The occurrence of aberrant methylation events in the LINC00886 TSS was more responsible for the down-expression of LINC00886. Over-expression of LINC00886 dramatically mitigated cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. LINC00886 may be associated with VEGFA/PI3K/AKT signaling pathways and epithelial-mesenchymal transition (EMT) process. CONCLUSIONS: We provide the first evidence of the involvement of LINC00886 in laryngeal carcinoma, which was downregulated due to methylation of the promoter region and served as tumor suppressor genes. LINC00886 is expected to become a novel biomarker in laryngeal carcinoma.

lncRNA RASSF8­AS1 suppresses the progression of laryngeal squamous cell carcinoma via targeting the miR­664b­3p/TLE1 axis.

Long non­coding (lnc)RNAs have been found to play a crucial role in tumor progression. The present study aimed to investigate the association between lncRNA RASSF8­AS1 and laryngeal squamous cell carcinoma (LSCC) and the underlying mechanisms. Reverse transcription­quantitative PCR was used to measure the mRNA expression level of RASSF8­AS1, microRNA(miR)­664b­3p and transducin­like enhancer of split 1 (TLE1) in LSCC. The associations between RASSF8­AS1 and miR­664b­3p, and between miR­664b­3p and TLE1 were investigated using a dual luciferase reporter assay, while the former was further verified using an RNA immunoprecipitation (RIP) assay. The association between RASSF8­AS1 and miR­664b­3p on cell biological functions was investigated in vitro using MTS, colony formation and Transwell assays. The RASSF8­AS1 mRNA expression level was decreased in LSCC cell lines and carcinoma tissues, while overexpression of RASSF8­AS1 reduced the migration, invasion and proliferation abilities of LSCC cells. Furthermore, luciferase and RIP assays confirmed that RASSF8­AS1 was a competitive endogenous (ce)RNA by sponging miR­664b­3p to activate TLE1. miR­664b­3p was negatively modulated by RASSF8­AS1; however, TLE1 was positively regulated by RASSF8­AS1. Functionally, RASSF8­AS1 acted as a ceRNA to upregulate TLE1 by sponging miR­664b­3p. In conclusion, the RASSF8­AS1/miR­664b­3p/TLE1 axis acts by suppressing LSCC progression and may provide a novel insight for the molecular mechanism of LSCC.

Quantification of uric acid in vasculature of patients with gout using dual-energy computed tomography.

BACKGROUND: Gout, caused by hyperuricemia and subsequent deposition of aggregated monosodium urate crystals (MSU) in the joints or extra-articular regions, is the most common inflammatory arthritis. There is increasing evidence that gout is an independent risk factor for hypertension, cardiovascular disease progression and mortality. AIM: To evaluate if dual energy computed tomography (DECT) could identify MSU within vessel walls of gout patients, and if MSU deposits within the vasculature differed between patients with gout and controls. This study may help elucidate why individuals with gout have increased risk for cardiovascular disease. METHODS: 31 gout patients and 18 controls underwent DECT scans of the chest and abdomen. A material decomposition algorithm was used to distinguish regions of MSU (coded green), and calcifications (coded purple) from soft tissue (uncoded). Volume of green regions was calculated using a semi-automated volume assessment program. Between-group differences were analyzed using Mann-Whitney U exact test and nonparametric rank regression. RESULTS: Gout patients had significantly higher volume of MSU within the aorta compared to controls [Median (Min-Max) of 43.9 (0-1113.5) vs 2.9 (0-219.4), P = 0.01]. Number of deposits was higher in gout patients compared to controls [Median (Min-Max) of 20 (0-739) vs 1.5 (0-104), P = 0.008]. However, the difference was insignificant after adjustment for age, gender, history of cardiovascular disease and diabetes. Increased age was positively associated with total urate volume (r s = 0.64; 95% confidence interval: 0.43-0.78). CONCLUSION: This pilot study showed that DECT can quantify vascular urate deposits with variation across groups, with gout patients possibly having higher deposition. This relationship disappeared when adjusted for age, and there was a positive relationship between age and MSU deposition. While this study does not prove that green coded regions are truly MSU deposition, it corroborates recent studies that show the presence of vascular deposition.

TGF-ß-induced long non-coding RNA MIR155HG promotes the progression and EMT of laryngeal squamous cell carcinoma by regulating the miR-155-5p/SOX10 axis.

Non­coding RNAs, particularly long non­coding RNAs (lncRNAs), play important roles in tumorigenesis. The miR­155 host gene (MIR155HG) lncRNA has been found to play a crucial role in tumor progression. However, the role of MIR155HG in laryngeal squamous cell carcinoma (LSCC) remains unclear. Thus, the aim of the present study was to explore the roles and underlying molecular mechanisms of action of MIR155HG and miR­155­5p in LSCC, in an effort to provide novel approaches for the antitumor therapy for LSCC. In the present study, the expression levels of miR­155­5p and MIR155HG were detected by reverse tran-scription­quantitative polymerase chain reaction. In addition, the biological functions of MIR155HG and miR­155­5p on LSCC were evaluated in vitro by MTS assay, colony formation assay and Transwell assays, and in vivo by tumorigenesis assays. It was revealed that MIR155HG and miR­155­5p were significantly upregulated in LSCC tissues, and were associated with the TNM stage, pathological differentiation and lymph node metastasis. Moreover, the knockdown of MIR155HG and miR­155­5p inhibited the proliferation, migration and invasion of LSCC cells, whereas their overexpression exerted the opposite effects in vitro and MIR155HG overexpression promoted tumorigenesis in vivo. Furthermore, MIR155HG downregulation reduced the expression level of miR­155­5p. The inhibitory effect of MIR155HG knockdown on malignant behavior was abrogated by miR­155­5p overexpression. Bioinformatics analysis and luciferase reporter assay confirmed that miR­155­5p contributed to the progression of LSCC by directly binding to the 3' untranslated region of SRY­related­HMG­box 10 (SOX10). In addition, MIR155HG and miR­155­5p were upregulated by the induction of transforming growth factor­ß (TGF­ß) and promoted the expression of mesenchymal markers synergistically. On the whole, the findings of the present study indicate a novel role of MIR155HG in the TGF­ß­induced EMT of LSCC cells by regulating EMT markers through the miR­155/SOX10 axis. The MIR155HG/miR­155­5p/SOX10 axis plays an important role in promoting the progression of LSCC and may thus serve as a potential therapeutic target for LSCC treatment.

Expression profile analysis identifies the long non-coding RNA landscape and the potential carcinogenic functions of LINC00668 in laryngeal squamous cell carcinoma.

In order to explore the differentially expressed long non-coding RNAs (lncRNAs) in laryngeal squamous cell carcinoma (LSCC), the GSE84957 lncRNA expression profile was included in the present study through data mining in the National Center for Biotechnology Information/Gene Expression Omnibus (NCBI/GEO). Then, the differentially expressed genes (DEGs) of LSCC (1646 lncRNAs and 2713 mRNAs, fold change ≥ 2, P ≤ 0.05) were identified from the GSE84957 dataset using bioinformatics analysis. Of the 10 selected differentially expressed lncRNAs, the expression of 7 lncRNAs were verified by qRT-PCR method. Then, LINC00668, a potential carcinogenic lncRNA, was screened out by narrowing down the screening criteria (fold change ≥ 4, P ≤ 0.01). Furthermore, correlation analysis demonstrated that expression levels of LINC00668 were associated with age, pathological differentiation degree, T stage, clinical stage and cervical lymph node metastasis. Moreover, a series of bioinformatics tools and in vitro experiments proved that knockdown of LINC00668 inhibited the proliferation, migration and invasion ability of LSCC cells. The present study identified the lncRNAs landscape of LSCC through data mining and bioinformatics analysis, and verified oncogenic LINC00668, which may play important roles in promoting LSCC cells proliferation, migration and invasion.

Screening and clinical significance of tumor markers in head and neck squamous cell carcinoma through bioinformatics analysis.

In order to identify potential diagnostic and prognostic biomarkers, and treatment targets for head and neck squamous cell carcinoma (HNSCC), the present study obtained the gene expression profiles in HNSCC through public data mining, and core genes were identified using a series of bioinformatics analysis methods and databases. A total of nine hub genes (SPP1, ITGA6, TMPRSS11D, MMP1, LAMC2, FAT1, ACTA1, SERPINE1 and CEACAM1) were identified to be significantly correlated with HNSCC. Furthermore, overall survival analysis demonstrated that the expression values of hub genes were associated with overall survival in HNSCC. Furthermore, certain of the identified genes, including, TMPRSS11D, ACTA1 and CEACAM1, have not been thoroughly investigated in HNSCC previously. Taken together, the nine hub genes obtained by screening in the present study may serve as potential tumor markers and important prognostic indicators for HNSCC.

Aberrant methylation-mediated downregulation of lncRNA SSTR5-AS1 promotes progression and metastasis of laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is among the most common malignant tumors with poor prognosis. Accumulating evidences have identified the important roles of long noncoding RNAs (lncRNAs) in the initiation and progression of various cancer types; however, the global lncRNAs expression profile for metastatic LSCC is limited. RESULTS: In the present study, we screen expression profiles of lncRNAs in advanced LSCC patients with paired tumor tissues and corresponding normal tissues by microarrays. We identify numerous differentially expressed transcripts, and after the necessary verification of the transcripts expression in expanded samples, we experimentally validate the expression patterns of the remarkable low expressed gene, SSTR5, and its antisense lncRNA, SSTR5-AS1. Downregulation of SSTR5 is detected in LSCC tissues and laryngeal carcinoma cells. Aberrant DNA hypermethylation of the CpG sites clustered in the exon 1 and accumulation of inactive histone modifications at SSTR5 promoter region may be epigenetic mechanisms for its inactivation in LSCC. SSTR5-AS1 may play antitumor role in LSCC and may be regulated by the hypermethylation of the same CpG sites with SSTR5. SSTR5-AS1 inhibits laryngeal carcinoma cells proliferation, migration, and invasion. SSTR5-AS1 increases the enrichment of MLL3 and H3K4me3 at the promoter region of SSTR5 by interacting with MLL3 and further induces the transcription of SSTR5. Furthermore, SSTR5-AS1 interacts with and recruits TET1 to its target gene E-cadherin to activate its expression. CONCLUSION: These findings suggest that the identified lncRNAs and mRNAs may be potential biomarkers in metastatic LSCC, and SSTR5-AS1 may act as a tumor suppressor as well as a potential biomarker for antitumor therapy.

Long-term Outcomes of Gastroenteropancreatic Neuroendocrine Tumors.

OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare but have been increasing in incidence. Limited data on the long-term outcomes of patients with these tumors are available. METHODS: In this study, we used population-based data from the National Cancer Institute to assess long-term disease-specific survival (DSS) of patients who have undergone surgery for nonmetastatic disease. All patients with NETs of the stomach, small intestine, colon, rectum, appendix, and pancreas diagnosed between 1988 and 2009 were identified from the Surveillance, Epidemiology and End Results registry. Staging was derived from Surveillance, Epidemiology and End Results data using the European Neuroendocrine Tumor Society guidelines. Cases with incomplete staging data were excluded, along with those with stage IV disease, or those who did not undergo surgical resection. RESULTS: Kaplan-Meier analyses were constructed to determine DSS. Analyses were further stratified according to tumor site, stage at diagnosis, and tumor grade. Overall, 13,348 patients with GEP-NETs meeting the inclusion criteria were identified. CONCLUSIONS: There were excellent outcomes for most GEP-NET patients, with a 20-year DSS of greater than 75% across all sites and stages. Pancreatic tumors had the worst outcomes, but DSS remains greater than 50% at 20 years.