摘要：
Ibrutinib is a BTK-targeted irreversible inhibitor. In this study, we demonstrate that ibrutinib potently inhibits SRC activity in a non-covalent manner via mass spectrometry and crystallography. The S345C mutation renders SRC to bind covalently with ibrutinib, and restores the potency of ibrutinib against the gatekeeper mutant. The co-crystal structure of ibrutinib/SRC shows Ser345 of SRC did not form covalent bond with ibrutinib, leading to a decrease of potency and loss of the ability to overcome the gatekeeper mutation of SRC. The X-ray crystallographic studies also provide structural insight into why ibrutinib behaves differently against gatekeeper mutants of different kinases.
摘要：
INTRODUCTION: Primary gastric diffuse large B-cell lymphoma (GDLBCL) is a heterogeneous disease in clinicopathological features and prognosis. Programmed death ligand-1 (PD-L1) and microRNA-34a (miR-34a) play crucial roles in GDLBCL progress. The purpose of this research is to explore the clinical significance of PD-L1 and miR-34a expression in GDLBCL. PATIENTS AND METHODS: The expressions of PD-L1 and miR-34a were examined by IHC and qRT-PCR in 109 patients who were diagnosed with GDLBCL and were treated with rituximab plus cyclophosphamide, doxorubicin, prednisone vincristine and prednisone chemotherapy (R-CHOP) from January 2010 to December 2018. RESULTS: PD-L1 level was significantly higher in tumor tissues than adjacent non-tumor tissues (60.5%, P<0.001), while the miR-34a level was just reversed (50.5%, P<0.001), which was negatively correlated (r=-0.524, P<0.001). Notably, PD-L1-positive and miR-34a-negative expressions were significantly correlated with the advanced Lugano stage of IIE-IV stage (P<0.001 and P<0.01), elevated serumal LDH levels (P<0.001 and P<0.05), B symptoms present (P<0.001 and P<0.001), non-GCB subtype (P<0.001 and P<0.001) and negative Bcl-2 expression (P<0.05 and P<0.001). PD-L1 high and miR-34a low expression groups had more patients with IPI scores of 2 or greater (P<0.001 and P<0.05) and poor R-IPI (P<0.01 and P<0.01). The complete response rate was upregulated in patients with negative PD-L1 and positive miR-34a expression after R-CHOP treatment. DISCUSSION: PD-L1 expression and miR-34a expression were significantly associated with clinicopathological characteristics and survival prognosis; they may serve as novel prognostic markers in GDLBCL patients who were treated with R-CHOP. Immunotherapies targeting PD-L1 and miR-34a pathway may have therapeutic potential in GDLBCL.
摘要：
Hypertriglyceridemia is a risk factor for a series of diseases, such as cardiovascular disease (CVD), diabetes and nonalcoholic fatty liver disease (NAFLD). Angiopoietin-like proteins (ANGPTLs) family, especially ANGPTL3, ANGPTL4 and ANGPTL8, which regulate lipoprotein lipase (LPL) activity, play pivotal roles in triglyceride (TG) metabolism and related diseases/complications. There are many transcriptional and post-transcriptional factors that participate in physiological and pathological regulation of ANGPTLs to affect triglyceride metabolism. This review is intended to focus on the similarity and difference in the expression, structural features, regulation profile of the three ANGPTLs and inhibitory models for LPL. Description of the regulatory factors of ANGPTLs and the properties in regulating the lipid metabolism involved in the underlying mechanisms in pathological effects on diseases will provide potential therapeutic approaches for the treatment of dyslipidemia related diseases.
关键词：
calcium activated potassium channel;interleukin 1beta;KCa2.3 protein;KCa3.1 protein;low density lipoprotein;messenger RNA;mitogen activated protein kinase p38;monoclonal antibody;toll like receptor 4;toll like receptor 4 monoclonal antibody;toll like receptor antagonist;transcription factor RelA;tumor necrosis factor;unclassified drug;IL1B protein, mouse;interleukin 1beta;intermediate conductance calcium activated potassium channel;Kcnn3 protein, mouse;Kcnn4 protein, mouse;low density lipoprotein;mitogen activated protein kinase p38;monoclonal antibody;oxidized low density lipoprotein;Rela protein, mouse;small conductance calcium activated potassium channel;Tlr4 protein, mouse;Tnf protein, mouse;toll like receptor 4;transcription factor RelA;tumor necrosis factor;animal experiment;animal model;animal tissue;Article;blood vessel function;controlled study;down regulation;endothelium dependent vasodilation;enzyme linked immunosorbent assay;experimental cardiovascular disease;gene expression;mesenteric artery;minimally modified low density lipoprotein endothelium dependent vasodilation dysfunction;minimally modified low density lipoprotein endothelium dependent vasodilation dysfunction;mouse;nonhuman;priority journal;protein blood level;reverse transcription polymerase chain reaction;TLR signaling;upregulation;vascular disease;vasodilatation;Western blotting;animal;blood;drug effect;female;genetics;immunology;Institute for Cancer Research mouse;male;mesenteric artery;metabolism;phosphorylation;signal transduction;vascular endothelium;vasodilatation;Animals;Antibodies, Monoclonal;Endothelium, Vascular;Female;Interleukin-1beta;Intermediate-Conductance Calcium-Activated Potassium Channels;Lipoproteins, LDL;Male;Mesenteric Arteries;Mice, Inbred ICR;p38 Mitogen-Activated Protein Kinases;Phosphorylation;Signal Transduction;Small-Conductance Calcium-Activated Potassium Channels;Toll-Like Receptor 4;Transcription Factor RelA;Tumor Necrosis Factor-alpha;Vasodilation
摘要：
Minimally modified low-density lipoprotein (mmLDL) is a risk factor for cardiovascular disease. This study was designed to investigate the effect of a Toll-like receptor 4 monoclonal antibody (TLR4 mAb) on mmLDL-induced endothelium-dependent vasodilation (EDV) impairment in mouse mesenteric arteries and to explore the underlying mechanism. Animals were divided into a normal control group, an mmLDL treatment group, and a TLR4 mAb intervention group. The serum concentrations of IL-1beta and TNF-alpha were detected using enzyme-linked immunosorbent assays (ELISAs). EDV function was measured using a microvascular tension tracing method. The protein levels and mRNA expression of IL-1beta and TNF-alpha in vascular tissue were detected using western blot analysis and reverse transcription polymerase chain reaction, respectively. TLR4 mAb improved mmLDL-induced EDV functional impairment in a dose-dependent manner. TLR4 mAb significantly upregulated KCa3.1 and KCa2.3 channel protein levels and downregulated TNF-alpha and IL-1beta expression. These effects were possibly associated with the competitive antagonism of TLR4 mAb on the TLR4 signaling pathway and the downstream NF-kappaB p65 and p38 MAPK pathways, which are activated by mmLDL. In conclusion, pretreatment with TLR4 mAb lessens mmLDL-induced EDV dysfunction and inhibits overexpression of inflammatory factors. Regulation of the TLR4 pathway, as well as its downstream NF-kappaB p65 and p38 MAPK pathways, may be an effective strategy for the prevention and treatment of cardiovascular diseases.
作者机构：
[Li, Jiexin; Peng, Yanxi; Wang, Hongsheng; Chen, Feng; Li, Zihan] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Key Lab Chiral Mol & Drug Discovery, Guangzhou 510006, Guangdong, Peoples R China.;[Tu, Jian; Li, Zihan] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Peng, Yanxi] Xiangnan Univ, Dept Basic Med, Chenzhou 423000, Hunan, Peoples R China.;[Chen, Zhuojia] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Peoples R China.;[Lin, Shuibin] Sun Yat Sen Univ, Affiliated Hosp 1, Ctr Translat Med, Guangzhou, Peoples R China.
通讯机构：
[Wang, Hongsheng] S;Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Key Lab Chiral Mol & Drug Discovery, Guangzhou 510006, Guangdong, Peoples R China.
摘要：
<jats:title>Abstract</jats:title><jats:p>Studies on biological functions of <jats:italic>N</jats:italic><jats:sup>6</jats:sup>-methyladenosine (m<jats:sup>6</jats:sup>A) modification in mRNA have sprung up in recent years. We find m<jats:sup>6</jats:sup>A can positively regulate the glycolysis of cancer cells. Specifically, m<jats:sup>6</jats:sup>A-sequencing and functional studies confirm that pyruvate dehydrogenase kinase 4 (PDK4) is involved in m<jats:sup>6</jats:sup>A regulated glycolysis and ATP generation. The m<jats:sup>6</jats:sup>A modified 5′UTR of <jats:italic>PDK4</jats:italic> positively regulates its translation elongation and mRNA stability via binding with YTHDF1/eEF-2 complex and IGF2BP3, respectively. Targeted specific demethylation of <jats:italic>PDK4</jats:italic> m<jats:sup>6</jats:sup>A by dm<jats:sup>6</jats:sup>ACRISPR system can significantly decrease the expression of PDK4 and glycolysis of cancer cells. Further, TATA-binding protein (TBP) can transcriptionally increase the expression of Mettl3 in cervical cancer cells via binding to its promoter. In vivo and clinical data confirm the positive roles of m<jats:sup>6</jats:sup>A/PDK4 in tumor growth and progression of cervical and liver cancer. Our study reveals that m<jats:sup>6</jats:sup>A regulates glycolysis of cancer cells through PDK4.</jats:p>
作者机构：
[Li, Jie; Tang, Hong-Xia; Qin, Xu-Ping] Univ South China, Peoples Hosp Chenzhou 1, Inst Pharm & Pharmacol, Chenzhou, Hunan, Peoples R China.;[Li, Jie] Southern Med Univ, Sch Pharm, Guangzhou, Guangdong, Peoples R China.;[Li, Jie] Univ South China, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
通讯机构：
[Li, Jie] U;Univ South China, Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
关键词：
STAT3;VSMCs;CVDs;proliferation;pathway
摘要：
<jats:sec><jats:title>Objectives</jats:title><jats:p>Cardiovascular disease (CVD) remains the primary cause of morbidity and mortality worldwide. The abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of CVD. The functional and phenotypic changes in vascular cells are mediated by complex signaling cascades that initiate and control genetic reprogramming. Many studies have demonstrated that signal transducer and activator of transcription 3 (STAT3) regulates a diverse array of functions relevant to atherosclerosis.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this review, we summarize the studies on the STAT3-mediated proliferation of VSMCs and subsequent CVDs such as hypertension, atherosclerosis, stroke, coronary artery disease, and myocardial infarction. Furthermore, we describe the general background of STAT3, its structure, function and regulation as well as the STAT3 signaling pathway. Finally, we highlight some potential issues and propose some solutions to these issues. Results and conclusions: STAT3 activation promotes the proliferation of VSMCs by regulating the transcription of genes. Studying the mechanism of VSMC proliferation induced by the STAT3 pathway is valuable for finding therapeutic targets for CVD.</jats:p></jats:sec>
摘要：
BACKGROUND: Abnormal reactivation of androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) mainly results from overexpression and down-regulation of AR. Sumoylation of AR can influence its function. However, regulation of AR sumoylation by SUMO E3 ligases PIASs to modify AR distribution and stability are not well understood. METHODS: We assessed the potential effect of SUMO3 modification on AR intracellular localization by immunostaining in AR-negative prostate cancer DU145 cells, and detected the effect of PIAS1/SUMO3 overexpression on AR sumoylation related degradation. Then we characterized AR sumoylation sites involved modified by SUMO3, and the key residue of PIAS1 involved in itself sumoylation and further mediated AR sumoylation (sumo3-conjugated), translocation and degradation. Finally we detected the recognition of PIAS1 (sumoylation ligase) to MDM2, a ubiquin ligase mediated AR degradation. RESULTS: We demonstrate that SUMO E3 ligase PIAS1, along with SUMO3, mediates AR cytosolic translocation and subsequent degradation via a ubiquitin-proteasome pathway. Although AR sumoylation occurs prior to ubiquitination, the SUMO-acceptor lysine 386 on AR, together with ubiquitin-acceptor lysine 845, contribute to PIAS1/SUMO3-induced AR nuclear export, ubiquitination and subsequent degradation. Moreover, PIAS1 itself is modified by SUMO3 overexpression, and mutation of SUMO-acceptor lysine 117 on PIAS1 can impair AR cytoplasmic distribution, demonstrating the essential role of sumoylated PIAS1 in AR translocation. We further determine that sumoylated PIAS1 interacts with AR lysine 386 and 845 to form a binary complex. Consistent with the effect on AR distribution, SUMO3 modification of PIAS1 is also required for AR ubiquitination and degradation by recruiting ubiquitin E3 ligase MDM2. CONCLUSION: Taken together, SUMO3 modification of PIAS1 modulates AR cellular distribution and stability. Our study provided the evidence the crosstalk between AR sumoylation and ubquitination mediated by PIAS1 and SUMO3.
期刊：
JOURNAL OF CELL BIOLOGY,2019年218(1):267-284 ISSN：0021-9525
通讯作者：
Zhang, Zhuohua
作者机构：
[Tian, Runyi; Lv, Lu; Wu, Yiming; Zhang, Zhuohua; Chen, Tingting; Tan, Ya; Cui, Jingyi; Shang, Shuai; Wang, Ruoxi; Han, Hailong; Chen, Fang; Tan, Jieqiong; Li, Jie; Guan, Xinjie] Cent S Univ, Xiangya Hosp, Inst Mol Precis Med, Changsha, Hunan, Peoples R China.;[Tian, Runyi; Lv, Lu; Wu, Yiming; Zhang, Zhuohua; Chen, Tingting; Tan, Ya; Cui, Jingyi; Shang, Shuai; Wang, Ruoxi; Han, Hailong; Chen, Fang; Tan, Jieqiong; Li, Jie; Guan, Xinjie] Cent S Univ, Ctr Med Genet, Changsha, Hunan, Peoples R China.;[Lu, Jiahong] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China.;[Zhang, Zhuohua] Univ South China, Sch Med, Dept Neurosci, Hengyang, Hunan, Peoples R China.
通讯机构：
[Zhang, Zhuohua] C;[Zhang, Zhuohua] U;Cent S Univ, Xiangya Hosp, Inst Mol Precis Med, Changsha, Hunan, Peoples R China.;Cent S Univ, Ctr Med Genet, Changsha, Hunan, Peoples R China.;Univ South China, Sch Med, Dept Neurosci, Hengyang, Hunan, Peoples R China.
关键词：
histone deacetylase 6;autophagosomes
摘要：
Mutations in ATP13A2 cause Kufor-Rakeb syndrome, an autosomal recessive form of juvenile-onset atypical Parkinson's disease (PD). Recent work tied ATP13A2 to autophagy and other cellular features of neurodegeneration, but how ATP13A2 governs numerous cellular functions in PD pathogenesis is not understood. In this study, the ATP13A2-deficient mouse developed into aging-dependent phenotypes resembling those of autophagy impairment. ATP13A2 deficiency impaired autophagosome-lysosome fusion in cultured cells and in in vitro reconstitution assays. In ATP13A2-deficient cells or Drosophila melanogaster or mouse tissues, lysosomal localization and activity of HDAC6 were reduced, with increased acetylation of tubulin and cortactin. Wild-type HDAC6, but not a deacetylase-inactive mutant, restored autophagosome-lysosome fusion, antagonized cortactin hyperacetylation, and promoted lysosomal localization of cortactin in ATP13A2-deficient cells. Mechanistically, ATP13A2 facilitated recruitment of HDAC6 and cortactin to lysosomes. Cortactin overexpression in cultured cells reversed ATP13A2 deficiency-associated impairment of autophagosome-lysosome fusion. PD-causing ATP13A2 mutants failed to rescue autophagosome-lysosome fusion or to promote degradation of protein aggregates and damaged mitochondria. These results suggest that ATP13A2 recruits HDAC6 to lysosomes to deacetylate cortactin and promotes autophagosome-lysosome fusion and autophagy. This study identifies ATP13A2 as an essential molecular component for normal autophagy flux in vivo and implies potential treatments targeting HDAC6-mediated autophagy for PD.
作者机构：
[李洁] The First People's Hospital of Chenzhou, Chenzhou, 423000, China;[秦旭平] Institute of Drug and Pharmacology, University of South China, Hengyang, 421001, China;[周楠] Medical College, Xi'an Jiaotong University, Xi'an, 710061, China;[林杰; 陈根] The First People's Hospital of Chenzhou, Chenzhou, 423000, China, Institute of Drug and Pharmacology, University of South China, Hengyang, 421001, China
通讯机构：
[Li, J.] T;The First People's Hospital of ChenzhouChina
关键词：
TLR4单克隆抗体;轻度氧化修饰低密度脂蛋白;炎症;肠系膜动脉;内皮依赖性舒张
摘要：
目的探讨预先使用TLR4单克隆抗体(TLR4mAb)对轻度氧化修饰低密度脂蛋白(mmLDL)诱发小鼠肠系膜动脉内皮依赖性舒张功能损伤的影响及作用机制。方法实验分为:空白对照组、mmLDL处理组、TLR4mAb干预组。采用ELISA方法测定血浆中白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α的浓度水平,微血管张力描记技术测定血管内皮依赖性舒张功能, Western blot技术和RT-PCR技术分别考察血管组织蛋白表达量和mRNA表达水平,透射电镜观察肠系膜动脉内皮细胞超显微结构。结果TLR4mAb剂量依赖性改善mmLDL损伤血管内皮依赖性舒张功能的损伤作用,显著上调KCa3.1-通道、KCa 2.3-通道蛋白表达和下调炎症因子TNF-α和IL-1β表达。TLR4mAb改善mmLDL损伤血管内皮细胞及内皮依赖性舒张功能,可能与其竞争性拮抗mmLDL激活TLR4信号转导通路及其下游的NF-κBp65和p-38MAPK通路有关。结论预先使用TLR4mAb可以减轻mmLDL所诱发的内皮细胞损伤和内皮依赖性舒张功能降低,以及抑制炎症因子的过度表达,调控TLR4通路及其下游的NF-κBp65和p-38MAPK通路可能是预防治疗心血管疾病的有效靶点。 <&wdkj&>OBJECTIVE To investigate the effect and mechanism of TLR4 monoclonal antibody (TLR4mAb) on mmLDL induced impairment of endothelium-dependent vasodilatation in mouse mesenteric artery. METHODS The experiment established three groups of normal saline group,mmLDL treatment group and TLR4mAb intervention group. The concentration of IL-1β and TNF-α in plasma was determined by enzyme-linked immunosorbent assay (ELISA) . Measurement of endothelium-dependent vasodilatation was achieved by microvascular tension mapping. Western blot and RT-PCR were used to investigate the expression level of protein and mRNA expressions in vascular tissues. In addition,ultra-structure of mesenteric artery endothelial cells was observed by transmission electron microscope. RESULTS TLR4mAb could improve the damage of mmLDL induced impairment of endothelium-dependent vasodilatation in a dose-dependent manner. Besides,TLR4mAb obviously up-regulated protein expressions in KCa 3.1-channel and KCa 2.3-channel,and down-regulated the expression of inflammatory factors TNF-α and IL-1β. Furthermore,the improvement of mmLDL impaired vascular endothelial cells and endothelium-dependent vasodilatation might be correlated with its competitive antagonism of mmLDL-activated TLR4 signal transduction pathway and its downstream NF-κBp65 and p-38 MAPK pathway. CONCLUSION Administration of TLR4mAb in advance can alleviate the impairment of endothelial cells and the decrease of endothelium-dependent vasodilatation induced by mmLDL,and inhibit the overexpression of inflammatory factors. Regulation of TLR4 pathway as well as its downstream NF-κBp65 and P-38 MAPK pathways may be effective targets for the prevention and treatment of cardiovascular diseases.
期刊：
Cancer Cell International,2019年19(1):1-13 ISSN：1475-2867
通讯作者：
Luo, Dixian
作者机构：
[Li, Jia; Hu, Zheng; Luo, Wenna; He, Rongzhang; Luo, Weihao; Duan, Lili; Luo, Dixian; Wang, Qingmei; Tan, Tan] Univ South China, Peoples Hosp Chenzhou 1, Natl & Local Joint Engn Lab High High Throughput, Translat Med Inst, Chenzhou 423000, Peoples R China.;[Luo, Dixian; Wang, Qingmei; Tan, Tan] Univ South China, Peoples Hosp Chenzhou 1, Ctr Clin Pathol, Chenzhou 423000, Peoples R China.;[He, Rongzhang] Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410078, Hunan, Peoples R China.
通讯机构：
[Luo, Dixian] U;Univ South China, Peoples Hosp Chenzhou 1, Natl & Local Joint Engn Lab High High Throughput, Translat Med Inst, Chenzhou 423000, Peoples R China.
摘要：
Background: The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported in the progression of various tumors. However, the potential biological roles and regulatory mechanisms of long non-coding RNAs in the development of colorectal cancer (CRC) have not yet been fully elucidated. Therefore, it is crucial to identify that lncRNAs can be used for the clinical prevention and treatment of CRC. Methods: In our previous work, we identificated a novel lncRNA, lncRNA-KAT7, and found that the expression of lncRNA-KAT7 in CRC tissues was significantly lower than that in matched normal intestinal tissues, and the expression in CRC cell lines was lower than that of normal intestinal epithelial cells (P < 0.05). Besides, the expression of lncRNA-KAT7 is negative associated with age, tumor size, tumor differentiation, lymph node metastasis of CRC patients. The potential biological effects and molecular mechanisms of lncRNA-KAT7 in CRC were evaluated using a series of CCK-8 assay, clone formation assay, EdU proliferation assay, scratch determination, transwell determination, western blot analysis, and nude subcutaneous tumorigenesis model construction cell and animal experiments. Results: The expression of lncRNA-KAT7 in CRC tissues was lower than that in matched normal tissues and normal intestinal epithelial cells (P < 0.05). Decreased expression of lncRNA-KAT7 is associated with clinicopathological features of poor CRC patients. In vitro experiments showed that up-regulation of lncRNA-KAT7 expression in CRC cells inhibited cell proliferation and migration. In vivo animal experiments showed that the lncRNA-KAT7 also inhibited tumor growth. Western blot analysis showed that the expression of lncRNA-KAT7 was up-regulated in HCT116 cells, the expression of E-cadherin increased, and the expression of Vimentin, MMP-2 and beta-catenin protein was down-regulated so did the phosphorylation NF-kappaB P65. The results confirm that the expression of lncRAN-KAT7 can inhibit the malignant phenotype of CRC cells. Conclusions: Up to now, as a novel lncRNA, lncRNA-KAT7 has not any relevant research and reports. The results confirm that the expression of lncRNA-KAT7 can inhibit the malignant phenotype of CRC cells. And it can be used as a new diagnostic biomarker and therapeutic target for the development of CRC.
作者机构：
[Li, Junyu] Canc Hosp Jiangxi Prov, Dept Radiotherapy, Nanchang 330029, Jiangxi, Peoples R China.;[Li, Yuehua; Wu, Xiaoping] Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Li, Ying] Hubei Canc Hosp, Dept Radiat Oncol, 116 Zhuodaoquan South Rd, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Li, Ying] H;Hubei Canc Hosp, Dept Radiat Oncol, 116 Zhuodaoquan South Rd, Wuhan 430079, Hubei, Peoples R China.
关键词：
biomarker;head and neck squamous cell carcinoma;long non-coding RNA;signature;survival
摘要：
Long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer and their aberrant expression has been associated with cancer diagnosis and prognosis, which suggests that they may be promising molecular biomarkers. However, understanding of the expression pattern of lncRNAs and their prognostic roles in head and neck squamous cell carcinoma (HNSCC) is relatively limited. In the current study, the prognostic value of lncRNA expression profiles in predicting the OS of patients with HNSCC was investigated by integrating clinical and profiling data from The Cancer Genome Atlas. A total of ten lncRNAs closely associated with the prognosis of patients with HNSCC were identified and may serve as novel biomarkers. This 10-lncRNA signature was used to classify patients into 2 groups with significantly different overall survival (OS) times (median OS time, 1.65 vs. 13.04 years; P<0.0001). This lncRNA signature was validated in an independent testing cohort. The results of multivariable Cox regression and stratification analyses revealed that the prognostic value of the 10-lncRNA signature was independent of other clinical and pathological factors for the survival of patients with HNSCC. Functional analysis demonstrated that lncRNA expression-based risk scoring may reflect the basic status of the immune response in the tumor microenvironment. The presented study demonstrated the value of a lncRNA signature as a potential biomarker to improve the clinical prognosis of patients with HNSCC.
