High eukaryotic initiation factor 5A2 expression predicts poor prognosis and may participate in the SNHG16/miR-10b-5p/EIF5A2 regulatory axis in head and neck squamous cell carcinoma.

BACKGROUND: This study attempted to investigate the significance of eukaryotic initiation factor 5A2 (EIF5A2) in the prognosis and regulatory network of head and neck squamous cell carcinoma (HNSCC). METHODS: EIF5A2 expression, prognostic information, and methylation levels of HNSCC were collected from the Cancer Genome Atlas (TCGA) database. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to determine EIF5A2 levels in HNSCC and normal tissue samples. R software was employed for expression analysis and prognosis assessment of EIF5A2 in HNSCC. A competing endogenous RNA (ceRNA) network was generated with the starBase database. Gene set enrichment analysis (GSEA) was used to determine the enriched physiological functions and network related to high expression of EIF5A2 in HNSCC. Immune infiltration-related outcomes were acquired from the CIBERSORT and Tumor Immune Estimation Resource (TIMER) database. RESULTS: EIF5A2 overexpression was observed in HNSCC and linked to poor progression-free survival and overall survival time. Cox regression analyses showed that EIF5A2 level was a stand-alone indicator of HNSCC patients' prognosis. A ceRNA network analysis highlighted the SNHG16/miR-10b-5p/EIF5A2 axis in EIF5A2 regulation. The GSEA results indicated that EIF5A2 was involved in complex signaling pathways. The CIBERSORT and TIMER databases revealed significant associations between EIF5A2 expression and immune cell infiltration. CONCLUSION: EIF5A2 overexpression may be a risk factor for prognosis in HNSCC and may be regulated by the SNHG16/miR-10b-5p/EIF5A2 axis.

5-Methylcytosine-related lncRNAs: predicting prognosis and identifying hot and cold tumor subtypes in head and neck squamous cell carcinoma.

BACKGROUND: 5-Methylcytosine (m5C) methylation is recognized as an mRNA modification that participates in biological progression by regulating related lncRNAs. In this research, we explored the relationship between m5C-related lncRNAs (mrlncRNAs) and head and neck squamous cell carcinoma (HNSCC) to establish a predictive model. METHODS: RNA sequencing and related information were obtained from the TCGA database, and patients were divided into two sets to establish and verify the risk model while identifying prognostic mrlncRNAs. Areas under the ROC curves were assessed to evaluate the predictive effectiveness, and a predictive nomogram was constructed for further prediction. Subsequently, the tumor mutation burden (TMB), stemness, functional enrichment analysis, tumor microenvironment, and immunotherapeutic and chemotherapeutic responses were also assessed based on this novel risk model. Moreover, patients were regrouped into subtypes according to the expression of model mrlncRNAs. RESULTS: Assessed by the predictive risk model, patients were distinguished into the low-MLRS and high-MLRS groups, showing satisfactory predictive effects with AUCs of 0.673, 0.712, and 0.681 for the ROCs, respectively. Patients in the low-MLRS groups exhibited better survival status, lower mutated frequency, and lower stemness but were more sensitive to immunotherapeutic response, whereas the high-MLRS group appeared to have higher sensitivity to chemotherapy. Subsequently, patients were regrouped into two clusters: cluster 1 displayed immunosuppressive status, but cluster 2 behaved as a hot tumor with a better immunotherapeutic response. CONCLUSIONS: Referring to the above results, we established a m5C-related lncRNA model to evaluate the prognosis, TME, TMB, and clinical treatments for HNSCC patients. This novel assessment system is able to precisely predict the patients' prognosis and identify hot and cold tumor subtypes clearly for HNSCC patients, providing ideas for clinical treatment.

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.

Identification of cuproptosis-related subtypes and characterization of the tumor microenvironment landscape in head and neck squamous cell carcinoma.

BACKGROUND: Cuproptosis is considered a novel copper-dependent cell death model. In this study, we established a novel scoring system based on 10 cuproptosis-related genes (CRGs) to predict the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC). METHODS: The RNA-seq data of HNSCC patients were downloaded from the GEO and TCGA databases and were merged into a novel HNSCC cohort. Multiomics landscape analyses were conducted, including tumor mutation burden (TMB), copy number variations and the interaction network of CRGs. Patients were then divided into different cuproptosis subtypes based on the expression of 10 CRGs and subsequently regrouped into novel gene clusters referring to differentially expressed genes. A cuproptosis score (CS) system was established using principal component analysis. The CIBERSORT, ssGSEA and ESTIMATE algorithms were used to assess the tumor immune microenvironment. Moreover, the immunotherapeutic and chemotherapeutic responses were assessed. RESULTS: Patients were divided into three cuproptosis subtypes and subsequently regrouped into three gene clusters, reflecting different immune infiltration. Assessed by the CS system, those with higher CSs exhibited worse prognosis and higher TMB frequency. Nevertheless, the immune-related analysis revealed patients in the low-CS group appeared immunosuppressive and easily suffered from immune escape. High CSs possibly show high expression of immune checkpoint genes and enhance chemotherapy sensitivity to cisplatin, docetaxel, and gemcitabine. CONCLUSION: We established a novel scoring system to predict the prognosis and immune landscape of HNSCC patients. This signature exhibits satisfactory predictive effects and the potential to guide comprehensive treatment for patients.

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.

The possible mechanism of Hippophae fructus oil applied in tympanic membrane repair identified based on network pharmacology and molecular docking.

OBJECTIVE: This study aimed to explore the mechanisms of Hippophae fructus oil (HFO) in the treatment of tympanic membrane (TM) perforation through network pharmacology-based identification. METHODS: The compounds and related targets of HFO were extracted from the TCMSP database, and disease information was obtained from the OMIM, GeneCards, PharmGkb, TTD, and DrugBank databases. A Venn diagram was generated to show the common targets of HFO and TM, and GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways. The PPI network and core gene subnetwork were constructed using the STRING database and Cytoscape software. A molecular docking analysis was also conducted to simulate the combination of compounds and gene proteins. RESULTS: A total of 33 compounds and their related targets were obtained from the TCMSP database. After screening the 393 TM-related targets, 21 compounds and 22 gene proteins were selected to establish the network diagram. GO and KEGG enrichment analyses revealed that HFO may promote TM healing by influencing cellular oxidative stress and related signaling pathways. A critical subnetwork was obtained by analyzing the PPI network with nine core genes: CASP3, MMP2, IL1B, TP53, EGFR, CXCL8, ESR1, PTGS2, and IL6. In addition, a molecular docking analysis revealed that quercetin strongly binds the core proteins. CONCLUSION: According to the analysis, HFO can be utilized to repair perforations by influencing cellular oxidative stress. Quercetin is one of the active compounds that potentially plays an important role in TM regeneration by influencing 17 gene proteins.

Construction of a necroptosis-related lncRNA signature to predict the prognosis and immune microenvironment of head and neck squamous cell carcinoma.

BACKGROUND: Previous studies have determined that necroptosis-related genes are potential biomarkers in head and neck squamous cell carcinoma (HNSCC). Herein, we established a novel risk model based on necroptosis-related lncRNAs (nrlncRNAs) to predict the prognosis of HNSCC patients. METHODS: Transcriptome and related information were obtained from TCGA database, and an nrlncRNA signature was established based on univariate Cox analysis and least absolute shrinkage and selection operator Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model, and a nomogram for survival prediction was established. Gene set enrichment analysis, immune analysis, drug sensitivity analysis, correlation with N6-methylandenosin (m6A), and tumor stemness analysis were performed. Furthermore, the entire set was divided into two clusters for further discussion. RESULTS: A novel signature was established with six nrlncRNAs. The areas under the ROC curves (AUCs) for 1-, 3-, and 5-year overall survival (OS) were 0.699, 0.686, and 0.645, respectively. Patients in low-risk group and cluster 2 had a better prognosis, more immune cell infiltration, higher immune function activity, and higher immune scores; however, patients in high-risk group and cluster 1 were more sensitive to chemotherapy. Moreover, the risk score had negative correlation with m6A-related gene expression and tumor stemness. CONCLUSION: According to this study, we constructed a novel signature with nrlncRNA pairs to predict the survival of HNSCC patients and guide immunotherapy and chemotherapy. This may possibly promote the development of individualized and precise treatment for HNSCC patients.

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.

Identification of several senescence-associated genes signature in head and neck squamous cell carcinoma.

BACKGROUND: As one of the core aging processes, cellular senescence is associated with tumorigenesis, growth, and immune modulation in cancers. Nevertheless, the prognosis of senescence-associated genes (SAGs) signature in head and neck squamous cell carcinoma (HNSCC) remains to be further evaluated. METHODS: The transcriptome and corresponding clinical datasets of SAGs in patients with HNSCC were downloaded from public databases. A new prognostic SAGs signature was established with least absolute shrinkage and selection operator discussion. Patients with HNSCC were fallen into two risk groups based on each sample's risk mark and the cutoff point. The survival analysis was extended to determine the predictive accuracy of the SAGs signature. Furthermore, the evaluation of SAGs signature was made according to clinicopathological characteristics, survival state, the infiltration of inflammatory cells, and efficacy of immunotherapy. RESULTS: 41 SAGs were recognized and adopted to establish the forecast signature. The survival analysis indicated that patients with HNSCC in the high-senescent score group had significantly reduced overall survival compared with those in the low-senescent score group. It was certified that the risk score of SAGs signature was a separate predicting agent for HNSCC applying Cox regression analysis. According to functional analysis, some immune-associated pathways were increased in the low-senescent score group significantly. High-senescent score group was correlated with poor clinicopathological characteristics, given less the infiltration of inflammatory cells state and worse immunotherapeutic effect. CONCLUSION: A new SAG signature predicting result and response to immunotherapy of HNSCC was identified. Cellular senescence may be a hidden target for HNSCC.

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.

Construction of an algorithm based on oncosis-related LncRNAs comprising the molecular subtypes and a risk assessment model in lung adenocarcinoma.

BACKGROUND: As an important non-apoptotic cell death method, oncosis has been reported to be closely associated with tumors in recent years. However, few research reported the relationship between oncosis and lung cancer. METHODS: In this study, we established an oncosis-based algorithm comprised of cluster grouping and a risk assessment model to predict the survival outcomes and related tumor immunity of patients with lung adenocarcinomas (LUAD). We selected 11 oncosis-related lncRNAs associated with the prognosis (CARD8-AS1, LINC00941, LINC01137, LINC01116, AC010980.2, LINC00324, AL365203.2, AL606489.1, AC004687.1, HLA-DQB1-AS1, and AL590226.1) to divide the LUAD patients into different clusters and different risk groups. Compared with patients in clsuter1, patients in cluster2 had a survival advantage and had a relatively more active tumor immunity. Subsequently, we constructed a risk assessment model to distinguish between patients into different risk groups, in which low-risk patients tend to have a better prognosis. GO enrichment analysis revealed that the risk assessment model was closely related to immune activities. In addition, low-risk patients tended to have a higher content of immune cells and stromal cells in tumor microenvironment, higher expression of PD-1, CTLA-4, HAVCR2, and were more sensitive to immune checkpoint inhibitors (ICIs), including PD-1/CTLA-4 inhibitors. The risk score had a significantly positive correlation with tumor mutation burden (TMB). The survival curve of the novel oncosis-based algorithm suggested that low-risk patients in cluster2 have the most obvious survival advantage. CONCLUSION: The novel oncosis-based algorithm investigated the prognosis and the related tumor immunity of patients with LUAD, which could provide theoretical support for customized individual treatment for LUAD patients.

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.

Tympanic membrane regeneration using platelet-rich fibrin: a systematic review and meta-analysis.

PURPOSE: Platelet-rich fibrin (PRF) results in satisfactory wound healing. This analysis focuses on assessing the effectiveness of PRF in the treatment of tympanic membrane (TM) perforations. MATERIALS AND METHODS: The literature was searched using PubMed, Embase, Cochrane Library and Web of Science databases from inception to February 28th, 2021. The following healing and hearing outcomes were measured: closure rate, pre-and postoperative auditory results, and incidence of postoperative infections. Data were pooled and expressed as the odds ratio (OR). RESULTS: Ten studies were eligible for qualitative review, and seven of them were included for the final quantitative comparison. The OR for the closure rate of acute perforations was 4.30 (95% CI 1.35-13.70, I2 = 0%), and the OR in the chronic subgroup was 5.42 (95% CI 2.57-11.43, I2 = 0%). The total OR value for the completed closure rate was 5.10 (95% CI 2.72-9.54, I2 = 0%), indicating that the utilization of PRF can enhance the closure of both acute and chronic perforations. The qualitative review did not find improved hearing results with the use of PRF. In addition to promoting closure, PRF can reduce the incidence of infections (OR = 0.14). The sensitivity analysis did not change the final results, and there was no publication bias in this analysis. CONCLUSION: PRF can increase the closure rate of acute perforations, enhance the survival rate of autografts in TM surgeries and reduce the incidence of infections. However, the literature indicates that PRF does not influence the hearing outcomes. This study shows that PRF is an effective agent for TM regeneration.

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.

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.

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.