A 5'-tiRNA fragment that inhibits proliferation and migration of laryngeal squamous cell carcinoma by targeting PIK3CD.

tRNA-derived small RNAs (tsRNAs) participate in several biological processes, including carcinogenesis. The correlations between tsRNAs and human cancers are attracting substantial attention. Nevertheless, the involvement of tsRNAs in laryngeal squamous cell carcinoma (LSCC) progression remains unclear. We constructed tsRNAs expression profiles in LSCC and adjacent normal tissues by next-generation sequencing. Interestingly, we identified a specific 5'-tiRNA fragment (tRF-33-Q1Q89P9L842205) that was significantly downregulated and was closely associated with lymph node metastasis and advanced stages of LSCC. Importantly, we found that tRF-33-Q1Q89P9L842205 suppressed cell growth, proliferation, migration, invasion and induced apoptosis in LSCC by directly silencing phosphoinositide 3-kinase catalytic subunit (PIK3CD). We speculated that tRF-33-Q1Q89P9L842205 is a potential diagnostic biomarker for LSCC and acts as a tumor suppressor by directly targeting PIK3CD.

Roles and clinical application of exosomal circRNAs in the diagnosis and treatment of malignant tumors.

Exosomes are microvesicles secreted by cells. They contain a variety of bioactive substances with important roles in intercellular communication. Circular RNA (circRNA), a type of nucleic acid molecule found in exosomes, forms a covalently bonded closed loop without 5' caps or 3' poly(A) tails. It is structurally stable, widely distributed, and tissue specific. CircRNAs mainly act as microRNA sponges and have important regulatory roles in gene expression; they are superior to other non-coding RNAs as molecular diagnostic markers and drug treatment targets. Exosomal-derived circRNAs in the body fluids of tumor patients can modulate tumor proliferation, invasion, metastasis, and drug resistance. They can be used as effective biomarkers for early non-invasive diagnosis and prognostic evaluation of tumors, and also represent ideal targets for early precision therapeutic intervention. This review provides a theoretical basis for exploring the applications of exosomal circRNAs in malignant tumor diagnosis and treatment. We describe the biological functions of exosomal circRNAs in the occurrence and development of malignant tumors, their potential utility in diagnosis and treatment, and possible mechanisms.

Identification of immune-related lncRNA panel for predicting immune checkpoint blockade and prognosis in head and neck squamous cell carcinoma.

PURPOSE: Immunotherapy is changing head and neck squamous cell carcinoma (HNSCC) treatment pattern. According to the Chinese Society of Clinical Oncology (CSCO) guidelines, immunotherapy has been deemed as first-line recommendation for recurrent/metastatic HNSCC, marking that advanced HNSCC has officially entered the era of immunotherapy. Long non-coding RNAs (lncRNAs) impact every step of cancer immunity. Therefore, reliable immune-lncRNAs able to accurately predict the immune landscape and survival of HNSCC are crucial to clinical management. METHODS: In the current study, we downloaded the transcriptomic and clinical data of HNSCC from The Cancer Genome Atlas and identified differentially expressed immune-related lncRNAs (DEir-lncRNAs). Further then, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to identify proper DEir-lncRNAs to construct optimal risk model. Low-risk and high-risk groups were classified based on the optimal cut-off value generated by the areas under curve for receiver operating characteristic curves (AUC), and Kaplan-Meier survival curves were utilized to validate the prediction model. We then evaluated the model based on the clinical factors, immune cell infiltration, and chemotherapeutic and immunotherapeutic efficacy between two groups. RESULTS: In our study, we identified 256 Deir-lncRNAs in HNSCC. A total of 18 Deir-lncRNA pairs (consisting of 35 Deir-lncRNAs) were used to construct a risk model significantly associated with survival of HNSCC. Cox proportional hazard regression analysis confirmed that our risk model could be served as an independent prognostic indicator. Besides, HNSCC patients with low-risk score significantly enriched of CD8+ T cell, and corelated with high chemosensitivity and immunotherapeutic sensitivity. CONCLUSION: Our risk model could be served as a promising clinical prediction indicator, effective discoursing of the immune cell infiltration of HNSCC patients, and distinguishing patients who could benefit from chemotherapy and immunotherapy.

ITGA5 is an independent prognostic biomarker and potential therapeutic target for laryngeal squamous cell carcinoma.

BACKGROUND: Integrin α5 (ITGA5) was involved in a variety of cancers. However, the role of ITGA5 in laryngeal squamous cell carcinoma (LSCC) remains unknown. METHODS: The expression of ITGA5 and the corresponding clinicopathological parameters of LSCC patients the TCGA database. Five datasets (GSE51985, GSE59102, GSE84957, GSE27020, and GSE65858) were downloaded from the GEO database as validation sets. Kaplan-Meier plotter, Cox regression analysis, and nomogram were performed to determine the prognostic value of ITGA5 in LSCC. GO, KEGG, and GSEA were used to explore the underlying biological functions of ITGA5 in LSCC. The algorithms ESTIMATE and CIBERSORT were adopted to evaluate the association between ITGA5 and the infiltration of the immune cells. The algorithm pRRophetic was used to estimate the response to chemotherapeutic drugs. RESULTS: The expression of ITGA5 was higher in the LSCC samples and linked to poor overall survival and recurrence-free survival. Further, the Cox regression analysis confirmed that high expression of ITGA5 was an independent unfavorable prognostic factor. The predictive performance of nomogram based on the expression of ITGA5 was accurate and practical. The functional enrichment analysis confirmed that ITGA5 was related to the construction of the components and structures of the extracellular matrix. Finally, patients with high ITGA5 expression were more likely to benefit from docetaxel and gemcitabine. CONCLUSION: The expression of ITGA5 was elevated in the LSCC and was a predictor for prognosis and chemotherapeutic response in LSCC patients.

Construction of an m6A-related lncRNA pair prognostic signature and prediction of the immune landscape in head and neck squamous cell carcinoma.

BACKGROUND: Mounting evidence indicates that aberrantly expressed N6-methylandenosine (m6A) modification regulators and long noncoding RNA (lncRNA) influence the development of head and neck squamous cell carcinoma (HNSCC). However, the prognosis of m6A-related lncRNA (mrlncRNA) in HNSCC has not yet been evaluated. METHODS: We retrieved transcriptome, somatic mutation, and clinical information from The Cancer Genome Atlas database and established a differently expressed mrlncRNA (DEmrlncRNA) pair signature based on least absolute shrinkage and selection operator Cox regression and multivariate Cox analyses. Each sample's risk score was computed premised on the signature, which accurately classified patients into low- and high-risk group by the cut-off point. The signature was evaluated from the perspective of survival, clinicopathological characteristics, tumor mutation burden (TMB), immune cell infiltration, efficacy of chemotherapeutics, tumor immune microenvironment, and immune checkpoint inhibitor (ICI)-related genes. RESULTS: 11 DEmrlncRNA pairs were identified and were used to construct the prediction signature. Kaplan-Meier plotter revealed a worse prognosis in high-risk patients over low-risk patients (log rank p < 0.001). According to multivariate Cox regression analysis, the hazard ratio of the risk score and 95% confidence interval of 1.722 and (1.488-1.992) (p < 0.001) were obtained. Furthermore, an increased risk score was associated with aggressive clinicopathological features, specific tumor immune infiltration status, increased expression of ICI-related genes, higher TMB, and higher chemotherapeutics sensitivity (all p < 0.05). CONCLUSION: This research demonstrated that the signature premised on DEmrlncRNA pairs was an efficient independent prognostic indicator and may provide a rationale for research on immunotherapeutic and chemotherapeutics strategies for HNSCC patients.

Arylsulfatase I is a prognostic biomarker for head and neck squamous cell carcinoma and Pan-cancer.

BACKGROUND: Sulfatase gene family members mediate various biological functions in tumor stroma and tumor cell environments. However, the expressions and prognostic value of Arylsulfatase I (ARSI), a sulfatase gene family member, in head and neck squamous cell carcinoma (HNSC) have not been fully established. METHODS: Arylsulfatase I expressions in pan-cancer were profiled using publicly available databases. Then, univariate Cox regression, Kaplan-Meier, and the Pearson's correlation analyses were performed to determine correlations between ARSI expressions and cancer prognosis, immune cell status, and drug sensitivity. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were used to assess the potential mechanisms underlying ARSI functions in HNSC. RESULTS: Arylsulfatase I was highly expressed in 15 cancer types, with significant expressions in HNSC. Elevated ARSI levels were associated with worse prognostic outcomes in HNSC patients. In addition, GSVA and GSEA showed that ARSI was highly involved in tumor cell escape and inflammatory responses. Expressions of ARSI negatively correlated with tumor mutation burden or microsatellite instability and positively correlated with immune-related genes. Elevated ARSI expressions conferred poor tolerance to daporinad and sinularin, but increased cell sensitivity to dasatinib and XAV939. CONCLUSION: Arylsulfatase I is a promising prognostic and therapeutic target for HNSC.

Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma.

BACKGROUND: Pyroptosis plays an essential role in tumor immune responses and inflammation related to chemotherapy. Herein, we studied the characteristic patterns of pyroptosis in head and neck squamous cell carcinoma (HNSCC) to determine their prognostic and therapeutic effects. METHODS: Consensus clustering analysis was performed to classify patients into pyroptosis or gene clusters. A novel pyroptosis score was constructed by principal component analysis. Kaplan-Meier survival curves were used to show the prognostic value. We also assessed the functional enrichment, tumor mutation burden, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between high and low pyroptosis score group. RESULTS: Two distinct pyroptosis clusters were defined based on the mRNA expression profiles of PRGs, which were related to immune activation in HNSCC. Notably, a pyroptosis score was constructed according to different expression gene signatures, and then, each HNSCC patient was classified into a low or high pyroptosis score group. Patients with low pyroptosis scores had better immunotherapeutic responses and higher sensitivities to chemotherapeutic agents (paclitaxel, docetaxel, and gemcitabine). Kaplan-Meier survival curves showed that the pyroptosis patterns were independent prognostic indicators regardless of the level of tumor mutation burden. CONCLUSIONS: Pyroptosis plays an essential role in immune infiltration in HNSCC. Quantifying the pyroptosis score of individual patients might suggest prognostic, immunotherapeutic, and chemotherapeutic strategies for HNSCC.

Expression profile and prognostic value of CXCR family members in head and neck squamous cell carcinoma.

BACKGROUND: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). METHODS: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features, and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). RESULTS: CXCRs were differentially expressed in HNSCC. As shown by Kaplan-Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. CONCLUSIONS: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.

The expression profile and clinical application value of hsa_circ_0016148 in head and neck squamous cell carcinoma.

BACKGROUND: Dysregulated circular RNAs (circRNAs) are involved in human cancers and may be used as biomarkers with the potential of clinical application. However, little is known regarding the mechanism of circRNAs and their clinical application value in head and neck squamous cell carcinoma (HNSCC). METHODS: In the current study, we established the profile of circRNAs in HNSCC using microarray and then measured the expression of hsa_circ_0016148 in 137 paired HNSCC tissues by qRT-PCR technique, analyzed the relationship between hsa_circ_0016148 and clinicopathological data, and investigated its diagnostic and prognostic value. The hsa_circ_0016148-miRNA-mRNA interaction network was predicted and constructed by Cytoscape. RESULTS: Our study showed a circRNA expression profile and confirmed downregulated hsa_circ_0016148 in HNSCC tissues (p = 2.64E-35). The hsa_circ_0016148 expression is remarkably correlated with lymph node metastasis (p = 0.001) and clinical stage (p = 0.029). Then, the area under the receiver characteristic curve (AUC) was 0.912 with 92% of sensitivity and 86.9% specificity, respectively. Besides, our study demonstrated that lower-expressed hsa_circ_0016148 could independently predict poorer overall survival of HNSCC patients (hazard ratio [HR] = 0.456; 95% confidence interval [CI] = 0.265-0.784; p = 0.005). The hsa_circ_0016148-miRNA-mRNA interaction network was constructed, which included a total of nine targeted miRNAs. CONCLUSION: Taken together, our results revealed that hsa_circ_0016148 might play a critical role in HNSCC tumorigenesis and may serve as an indicator with the potential of diagnosis and prognosis for HNSCC.

Translation role of circRNAs in cancers.

Circular RNAs (circRNAs) constitute a class of covalently closed RNA molecules. With the continuous advancement of high-throughput sequencing technology and bioinformatics tools, many circRNAs have been identified in various human tissues and cell lines. Notably, recent studies have indicated that some circRNAs have translational functions. Internal ribosome entry sites and the N6-methyladenosine modification mediate cap-independent translation. This review describes these two translation mechanisms and verification methods at the molecular level. Databases (including ORF Finder, Pfam, BLASTp, CircRNADb, CircBase, CircPro, CircCode, IRESite, IRESbase) were used to analyze whether circRNAs have the structural characteristic of translation. CircRNA minigene reporter system containing green fluorescent protein (GFP) confirmed the translation potential of circRNAs. Also, we briefly summarize the roles of proteins/peptides encoded by circRNAs (circFBXW7, circFNDC3B, circLgr4, circPPP1R12A, circMAPK1, circß-catenin, circGprc5a, circ-SHPRH, circPINTexon2, circAKT3) that have been verified thus far in human cancers (triple-negative breast cancer, colon cancer, gastric cancer, hepatocellular carcinoma, bladder cancer, glioblastoma). Those findings suggest circRNAs have a great implication in translation of the human genome.

Tissue engineering of the larynx: A contemporary review.

OBJECTIVE: Tissue engineering has been a topic of extensive research in recent years and has been applied to the regeneration and restoration of many organs including the larynx. Currently, research investigating tissue engineering of the larynx is either ongoing or in the preclinical trial stage. METHODS: A literature search was performed on the Advanced search field of PubMed using the keywords: "(laryncheal tissue engineering) AND (cartilage regeneration OR scaffolds OR stem cells OR biomolecules)." After applying the selection criteria, 65 articles were included in the study. RESULTS: The present review focuses on the rapidly expanding field of tissue-engineered larynx, which aims to provide stem cell-based scaffolds combined with biological active factors such as growth factors for larynx reconstruction and regeneration. The trend in recent studies is to use new techniques for scaffold construction, such as 3D printing, are developed. All of these strategies have been instrumental in guiding optimization of the tissue-engineered larynx, leading to a level of clinical induction beyond the in vivo animal experimental phase. CONCLUSIONS: This review summarizes the current progress and outlines the necessary basic components of regenerative laryngeal medicine in preclinical fields. Finally, it considers the design of scaffolds, support of growth factors, and cell therapies toward potential clinical application.

tRNAIni CAT inhibits proliferation and promotes apoptosis of laryngeal squamous cell carcinoma cells.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) brings a heavy blow to the patient's voice. Transfer RNA (tRNA) is a common RNA, the roles of tRNAs in LSCC are largely unknown. METHODS: The tRNA expression profile in LSCC tissues and adjacent normal tissues was measured by a tRNA qRT-PCR array. The expression level of tRNAIni CAT in LSCC tissues and plasmas was detected by qRT-PCR. The receiver operating characteristic (ROC) curve was established. tRNAIni CAT was upregulated by a lentivirus vector in the LSCC cell line. Moreover, tRNAIni CAT was upregulated in LSCC xenograft nude mouse model and the xenografts were used for pathological analysis and transmission electron microscope (TEM) observation. RESULTS: The top 10 upregulated tRNAs were tRNALys CTT -1, tRNALeu TAA , tRNAPhe GAA , tRNALeu CAG , tRNATyr ATA , tRNAMet CAT , tRNATyr GTA -1, tRNAThr CGT , tRNATyr GTA -2, tRNAAla AGC ; and the top 10 downregulated tRNAs were tRNAIni CAT , mt-tRNAGlu TTC , tRNAVal CAC -3, mt-tRNATrp TCA , mt-tRNATyr GTA , mt-tRNALys TTT , mt-tRNAThr TGT , mt-tRNAAsp GTC , mt-tRNAAsn GTT , mt-tRNAPro TGG . tRNAIni CAT was downregulated in LSCC tissues and plasma. The area under the ROC curve (AUC) in LSCC tissues and the plasma of patients with LSCC was 0.717 and 0.808, respectively. tRNAIni CAT inhibited LSCC cell proliferation and promoted apoptosis. The in vivo results showed that tRNAIni CAT inhibited the growth of the xenografts and promoted apoptosis. CONCLUSIONS: This is the first study to provide tRNA expression profiles for LSCC tissues. tRNAIni CAT may be used as a new biomarker for the early diagnosis of LSCC. tRNAIni CAT inhibits cell proliferation and promotes apoptosis in vitro and in vivo.

Expression of the long noncoding RNA RP11-169D4.1-001 in Hypopharyngeal Squamous cell carcinoma tissue and its clinical significance.

BACKGROUND: Increased research efforts have demonstrated that lncRNAs are associated with multiple head and neck tumors and play important roles in cancer. We previously found that RP11-169D4.1-001 plays a tumor-suppressive role in laryngeal cancer, but its function in human hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. Thus, this research aimed to analyze the relationship between RP11-169D4.1-001 expression and HSCC clinicopathological features. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression of RP11-169D4.1-001 in 70 pairs of HSCC and adjacent normal tissues. RESULTS: The expression level of RP11-169D4.1-001 in HSCC tissues was significantly lower than that in adjacent normal tissues (P = .001). The expression of RP11-169D4.1-001 had no significant relationship with tumor differentiation, stage, smoking, drinking, age, tumor location, or treatment. RP11-169D4.1-001 expression was associated with T category (P = .008) and lymph node metastasis (P = .001). Survival data were assessed by Kaplan-Meier curves. Patients with high RP11-169D4.1-001 expression were found to have a shorter overall survival than patients with low RP11-169D4.1-001 expression. Multivariate analysis also indicated that target RNA was an independent factor for prognosis. The ROC curve was constructed to clarify the diagnostic value of RP11-169D4.1-001. CONCLUSIONS: RP11-169D4.1-001 may serve as a new biomarker and potential drug target and can be used as a new biomarker and a potential drug target for the detection and treatment of hypopharyngeal cancer, respectively. Furthermore, RP11-169D4.1-001 expression may be an independent prognostic factor affecting the survival of hypopharyngeal cancer patients.

High P4HA1 expression is an independent prognostic factor for poor overall survival and recurrent-free survival in head and neck squamous cell carcinoma.

BACKGROUND: Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) plays a critical role in modulating the extracellular matrix and promoting tumor progression in various cancers. However, the association between P4HA1 and head and neck squamous cell carcinomas (HNSCC) has not been thoroughly elucidated to date. METHODS: P4HA1 mRNA and protein expression in cancer and normal tissues were analyzed using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and Human Protein Atlas databases. Quantitative PCR was applied to determine P4HA1 mRNA expression levels in 162 paired HNSCC and adjacent normal tissues. The cBioPortal for Cancer Genomics was utilized to explore P4HA1 genetic alterations in HNSCC. Then, KEGG analysis of P4HA1 co-expressed genes in HNSCC was conducted using ClueGo in Cytoscape. RESULTS: P4HA1 mRNA and protein levels were significantly increased in HNSCC tissues compared with normal tissues. High P4HA1 expression in HNSCC tissues was significantly associated with tumor category, lymphatic metastasis and pathological stage. The area under summary receiver operating characteristic curve of TCGA and validation cohort was 0.887 and 0.883, respectively. Moreover, elevated P4HA1 expression was associated with unfavorable OS (HR: 1.728, P = .001) and RFS (HR: 2.025, P = .002) in HNSCC patients. CONCLUSIONS: This integrated analysis provides strong evidence that increasing P4HA1 expression is significantly associated with the carcinogenesis of HNSCC. Additionally, high P4HA1 expression serves as both diagnostic biomarker and independent prognostic factor for poor OS and RFS in HNSCC patients.

Significant association between DHFR promoter methylation and ischemic stroke in a Chinese hypertensive population.

OBJECTIVE: DHFR encodes dihydrofolate reductase, a major enzyme in the metabolism of folate, and is a candidate gene for ischemic stroke (IS). Therefore, we aimed to investigate the association between DHFR promoter methylation and IS in a Chinese population with primary hypertension. METHODS: Quantitative methylation-specific PCR was used to measure the level of DHFR promoter methylation. A multivariate logistic regression model was used to investigate the association between DHFR promoter methylation and IS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of DHFR promoter methylation for IS. RESULTS: The level of methylation of the DHFR promoter in the IS group was significantly lower than that in the hypertensive group (median [interquartile range]: 9.11 [2.81-16.20] vs 24.94 [7.16-56.45], P < .001). DHFR promoter methylation and homocysteine (Hcy) levels were both related to IS, with an ORs (95% CI) of 0.976 (0.967-0.984) and 1.057 (1.027-1.108), respectively. The areas under the curve for the diagnosis of DHFR promoter hypomethylation in IS were 0.603 (95% CI, 0.527-0.678) in men and 0.754 (95% CI, 0.693-0.815) in women. A dual-luciferase reporter assay revealed that the target sequence in the DHFR promoter upregulated gene expression. CONCLUSION: There is a significant association between methylation of the DHFR promoter and IS in this Chinese hypertensive population. Hypomethylation of the DHFR promoter may serve as a novel marker for the diagnosis of IS in women.

Tumor suppression effect of targeting periostin with siRNA in a nude mouse model of human laryngeal squamous cell carcinoma.

BACKGROUND: The incidence of laryngeal carcinoma is increasing, however, the mechanism is not fully understood. We aimed to investigate the efficacy of periostin gene silencing by siRNA on tumor inhibition, in a novel nude mouse model of human laryngeal squamous cell carcinoma, and to explore possible inhibitory mechanisms. METHODS: Tumors were established in nude mice by transplantation of LSCC AMC-HN-8 cell line. Forty-eight nude mice were randomly divided into groups of eight each, and treated with high (1.0 OD) or low (0.5 OD) doses of periostin-siRNA or appropriate control solutions. Tumor growth was observed and used to calculate an inhibition rate (%). Routine pathological and electron microscopic examination were used to determine tumor apoptosis and proliferation. Changes in periostin mRNA and protein levels were analyzed. RESULTS: Tumor growth was significantly inhibited in mice treated by high dose periostin-siRNA compared to untreated and those treated with low dose periostin-siRNA (P < 0.05). Pathological examination showed increased tumor necrosis and apoptotic changes in treated mice, which was confirmed by electron microscopy. Periostin mRNA and protein expression were significantly reduced in tumors from mice treated with high dose periostin-siRNA, compared to controls and low-dose periostin-siRNA treatment groups (P < 0.05). CONCLUSION: Periostin silencing was associated with growth inhibition of tumor cells in a nude mouse model of LSCC. The underlying mechanism may be due to receptor-mediated induction of relevant signal transduction pathways that modulate the microenvironment needed for cancer cell survival. Periostin is expected to become a new target for cancer therapy.

The clinical significance of HOXA9 promoter hypermethylation in head and neck squamous cell carcinoma.

BACKGROUND: The purpose of the current study was to assess the association between HOXA9 (homeobox A9) promoter methylation and head and neck squamous cell carcinoma (HNSCC) and its diagnostic value. METHODS: Quantitative methylation-specific PCR (qMSP) was applied to measure HOXA9 promoter methylation levels in 145 paired HNSCC and corresponding normal tissue samples. Data from the Cancer Genome Atlas (TCGA) database (n = 578; 528 HNSCC and 50 normal) were also analyzed. RESULTS: Significantly higher levels of HOXA9 promoter methylation were detected in HNSCC, compared with normal, tissues (our cohort: P = 1.06E-35; TCGA cohort: P = 3.06E-39). Moreover, HOXA9 methylation was significantly increased in patients with advanced tumor (T) stage, lymph node metastasis, and advanced clinical stage. Areas under the receiver characteristic curves (AUCs) based on our cohort and TCGA data were 0.930 and 0.967, respectively. CONCLUSION: In summary, our study reveals that HOXA9 promoter hypermethylation contributes to the risk of HNSCC and its progression and metastasis. Additionally, HOXA9 hypermethylation is a potential biomarker for the early diagnosis and screening of patients with HNSCC.

ESRRG promoter hypermethylation as a diagnostic and prognostic biomarker in laryngeal squamous cell carcinoma.

BACKGROUND: Estrogen-related receptor gamma (ESRRG) has been identified as a tumor suppressor gene in several cancers. We aimed to evaluate ESRRG promoter methylation in laryngeal squamous cell carcinoma (LSCC) and its relative clinical value in LSCC. METHODS: Bisulfite pyrosequencing assays were performed on 91 pairs of tumor and paracancer tissues from LSCC patients in China. The diagnostic value and overall survival (OS) were analyzed descriptively by receiver operating characteristic (ROC) curves and the Kaplan-Meier methods, respectively. RESULTS: The ESRRG promoter was more frequently hypermethylated in tumor tissues than in adjacent tissues (P < 0.01). ESRRG promoter methylation was significantly increased in advanced T stage tumors (P < 0.01) and advanced clinical stage patients (P < 0.01). Moreover, the area under the ROC curve (AUC) value (0.81) indicated high discrimination accuracy. Furthermore, ESRRG hypermethylation was associated with poor OS, as confirmed by Kaplan-Meier survival curves (P < 0.01). CONCLUSION: Our study indicated that ESRRG promoter hypermethylation contributed to LSCC-related risks, primarily tumor progression and survival prognosis, in patients. ESRRG promoter methylation could, therefore, be a diagnostic and prognostic biomarker in LSCC.

[Fabrication of hydrophilic medical catheter with hydrogel grafting and the in vivo evaluation of its histo-compatibility].

The biocompatible hydrogel was fabricated under suitable conditions with natural dextran and polyethylene glycol (PEG) as the reaction materials. The oligomer (Dex-AI) was firstly synthesized with dextran and allylisocyanate (AI). This Dex-AI was then reacted with poly (ethyleneglycoldiacrylate) (PEGDA) under the mass ratio of 4∶6 to get hydrogel (DP) with the maximum water absorption of 810%. This hydrogel was grafted onto the surface of medical catheter via diphenyl ketone treatment under ultraviolet (UV) initiator. The surface contact angle became lower from (97 ± 6.1)° to (25 ± 4.2)° after the catheter surface was grafted with hydrogel DP, which suggests that the catheter possesses super hydrophilicity with hydrogel grafting. The in vivo evaluation after they were implanted into ICR rats subcutaneously verified that this catheter had less serious inflammation and possessed better histocompatibility comparing with the untreated medical catheter. Therefore, it could be concluded that hydrogel grafting is a good technology for patients to reduce inflammation due to catheter implantation, esp. for the case of retention in body for a relative long time.

The Association and Clinical Significance of CDKN2A Promoter Methylation in Head and Neck Squamous Cell Carcinoma: a Meta-Analysis.

BACKGROUND/AIMS: The association between cyclin-dependent kinase inhibitor 2A (CDKN2A) hypermethylation and head and neck squamous cell carcinoma (HNSCC) risk has been investigated by a number of studies. However, these studies have not demonstrated consistent results. Moreover, the role of CDKN2A methylation in HNSCC carcinogenesis and its clinical significance remain unclear. METHODS: We performed a systematic meta-analysis based on 72 articles (including 3399 HNSCCs, 668 premalignant lesions, and 2393 normal controls) from the PubMed, Google Scholar, Web of Science, Embase, China National Knowledge Infrastructure and Wanfang databases. RESULTS: Our study showed a significant increase in the frequency of CDKN2A methylation during HNSCC carcinogenesis (HNSCC vs. normal controls, odds ratio (OR) = 6.72, P < 0.01; HNSCC vs. precancerous lesions, OR = 1.89, P < 0.05; precancerous lesions vs. normal controls, OR = 14.70, P < 0.01). Moreover, CDKN2A methylation was significantly associated with gender (OR = 1.34; P < 0.05) and lymph node metastasis (OR = 2.32; P < 0.01). The area under summary receiver operating characteristic curve (AUC) for diagnosis of HNSCC based on all samples and saliva sample subgroup were 0.77 and 0.96, respectively. Additionally, CDKN2A hypermethylation was significantly associated with shorter overall survival (OS) (hazard ratio (HR) = 1.01, P < 0.05) and recurrence-free survival (RFS) (HR = 1.77, P < 0.05). CONCLUSION: Our findings indicate CDKN2A methylation is involved in the carcinogenesis, progression, and metastasis of HNSCC. Furthermore, methylated CDKN2A could be a potential diagnostic and prognostic biomarker for HNSCC.