Nomogram Model Based on Iodine Nutrition and Clinical Characteristics of Papillary Thyroid Carcinoma to Predict Lateral Lymph Node Metastasis.

OBJECTIVE: Preoperative evaluation of lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC) has been one of the major clinical challenges. This study aims to develop and validate iodine nutrition-related nomogram models to predict lateral cervical lymph node metastasis in patients with PTC. METHODS: This is a retrospective study. Urinary iodine concentration (UIC) and serum iodine concentration (SIC) were measured in 187 LLNM patients and 289 non-LLNM (NLLNM) patients. All patients were randomized 3:1 into the training cohort (n = 355) and the validation cohort (n = 121). Using logistic regression analysis, we analyzed the influence of iodine nutrition-related factors and clinicopathological characteristics on LLNM in PTC patients. Lasso regression method was used to screen risk factors and construct a nomogram for predicting LLNM. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) of the nomogram models were carried out for the training and validation cohorts. RESULTS: Gender, SIC, smoking history, drinking history, family history of PTC, multifocality, bilateral or unilateral tumors, TSH, Tg, and tumor size were included in the nomogram model predicting LLNM, with an area under the curve (AUC) of .795. The nomogram model showed good calibration and clinical benefit in both the training and validation cohorts. CONCLUSION: The nomogram model based on iodine nutrition and other clinicopathological features is effective for predicting the lateral lymph node metastasis in PTC patients.

Assessment of immune status of laryngeal squamous cell carcinoma can predict prognosis and guide treatment.

BACKGROUND: In the past few years, immunotherapy has changed the way we treat solid tumors. People pay more and more attention to the immune microenvironment of laryngeal squamous cell carcinoma (LSCC). In this study, our immunotherapy research took advantage of the clinical database and focused our in-depth analysis on the tumor microenvironment (TME). METHODS: This study evaluated the relationship between the clinical outcome and the local tissue and overall immune status in 412 patients with primary LSCC. We constructed and validated a risk model that could predict prognosis, assess immune status, identify high-risk patients, and develop personalized treatment plans through bioinformatics. In addition, through immunohistochemical analysis, we verified the differential expression of CTSL and KDM5D genes with the largest weight coefficients in the model in LSCC tissues and their influence on the prognosis and tumor-infiltrating lymphocytes (TILs). RESULTS: We found that interstitial tumor-infiltrating lymphocytes, tumor parenchymal-infiltrating lymphocyte volume, tumor infiltrates lymphocytes of frontier invasion, and the platelet-to-lymphocyte ratio (PLR) were independent factors affecting the prognosis of patients with LSCC. A novel risk model can guide clinicians to accurately predict prognosis, identify high-risk patients, and formulate personalized treatment plans. The differential expression of genes such as CTSL and KDM5D has a significant correlation with the TILs of LSCC and the prognosis of patients. CONCLUSION: Local and systemic inflammatory markers in patients with laryngeal squamous cell carcinoma are reliable prognostic factors. The risk model and CTSL, KDM5D gene have important potential research value.

Prognostic value of platelet distribution width and mean platelet volume in patients with laryngeal cancer.

Aims: To investigate the prognostic relevance of platelet volume indices for survival in laryngeal cancer. Patients & methods: The study included 640 patients with laryngeal cancer. We analyzed the optimal cutoff values through receiver operating characteristic analysis, then analyzed the univariate factor and multivariate variables. Kaplan-Meier curves and log-rank tests were conducted to compare the overall survival (OS) and recurrence-free survival rates between the groups. Results: In multivariate analysis, elevated platelet distribution width (PDW) and PDW/platelet count ratio were significantly correlated with poor prognosis for OS; however, elevated mean platelet volume (MPV) and MPV/platelet count ratio suggested a notable correlation with favorable prognosis for OS. Meanwhile, elevated PDW and decreased MPV were significantly correlated with poor prognosis for recurrence-free survival. Conclusions: Our findings indicate that elevated PDW and decreased MPV could serve as independent biomarkers for worse survival in laryngeal cancer.

High Iodine Nutrition May Be a Risk Factor for Cervical Lymph Node Metastasis in Papillary Thyroid Cancer Patients.

PURPOSE: The aim of this study was to retrospectively identify the effect of iodine on the papillary thyroid cancer (PTC) process and investigate the risk clinicopathologic characteristics of cervical lymph node metastasis (CLNM) for achieving a better preventive strategy of PTC. METHODS: Totally 187 patients with CLNM and 279 without CLNM (NCLNM) were enrolled, and their urinary iodine concentration (UIC) and serum iodine concentration (SIC) were measured. Logistic regressions were used to reveal the effects of iodine nutrition on the CLNM status of PTC. RESULTS: The levels of thyroid-stimulating hormone (TSH) and thyroglobulin (TG) were higher in the CLNM group than in the NCLNM group. UIC and SIC were positively correlated, and both of them were correlated with TSH, free thyroxine, and TG. The proportions of UIC >300 µg/L and of SIC >90 µg/L were higher in the CLNM than in the NCLNM. Logistic analysis showed that SIC >90 µg/L was an independent predictor for CLNM in PTC. Additionally, age ≥45, female, TG, multifocality, and diameter of cancer invasion >1 cm also affected CLNM status in PTC, and their logistic regression model showed a certain diagnostic accuracy (area under the receiver-operating characteristic curve = 0.72). CONCLUSIONS: Relatively high iodine nutrition seemed to be a significant risk factor for the occurrence of CLNM in PTC and may promote lymphatic metastasis in PTC.

Histone deacetylase 1 regulates the malignancy of oral cancer cells via miR-154-5p/PCNA axis.

Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in oral cancer cells are not well known. Our present study found that the HDAC1 was over expressed in oral squamous cell carcinoma (OSCC) cells and tissues. Targeted inhibition of HDAC1 via its specific inhibitor PCI24781 or siRNA can inhibit the proliferation of OSCC cells and increase their sensitivity to the chemo-sensitivity such as doxorubicin treatment. HDAC1 can regulate the expression of proliferating cell nuclear antigen (PCNA) via decreasing its mRNA stability. While over expression of PCNA can attenuate HDAC1 inhibition induced suppression of cell proliferation. We checked the expression of various miRNAs which can target the 3'UTR of PCNA. Results showed that HDAC1 can negative regulate the expression of miR-154-5p, inhibitor of miR-154-5p can attenuate PCI24781 treatment decreased PCNA expression and cell proliferation. Collectively, our present study suggested that HDAC1 can promote the growth and progression of OSCC via regulation of miR-154-5p/PCNA signals.

Prognostic Significance of Lactate Dehydrogenase in Patients Undergoing Surgical Resection for Laryngeal Squamous Cell Carcinoma.

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.

HOXA11-AS promotes the progression of oral squamous cell carcinoma by targeting the miR-518a-3p/PDK1 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are promising therapeutic molecules of cancer. Here we aim to study the therapeutic effect and mechanism of a lncRNA, HOXA11-AS, in oral squamous cell carcinoma (OSCC). METHODS: OSCC tissues and adjacent matched paraneoplastic normal tissues used in this study were collected from 42 OSCC patients. The significant downregulation or upregulation of HOXA11-AS expression in OSCC cells was confirmed by quantitative real-time PCR (qRT-PCR). Bioinformatics analysis of StarBase were performed to investigate the potential microRNAs mediated by HOXA11-AS. HOXA11-AS-transfected cells or control cells were subcutaneously injected into nude mice to further determine the effects of HOXA11-AS on OSCC progression in vivo. RESULTS: qRT-PCR analysis indicated that HOXA11-AS expression was significantly upregulated in OSCC tissues. Functional studies revealed that HOXA11-AS significantly promotes cell proliferation, reduces the percentage of G0/G1 phase cells and enhances the cell invasion in OSCC. Bioinformatics analysis suggested that a microRNA (miRNA), miR-518a-3p, is as a target of HOXA11-AS. Alteration of miR-518a-3p levels by HOXA11-AS transduced to changes in PDK1 expression. In a mouse model of OSCC, HOXA11-AS overexpression promoted tumor growth, concomitant with reduced miR-518a-3p expression and increased PDK1 expression. CONCLUSION: Taken together, our study demonstrates that HOXA11-AS/miR-518a-3p/PDK1 axis is an important regulator of OSCC progression and may serve as a potential therapeutic target in OSCC. HARMU20150128, registered at Jan, 28 2018.

BCL2 and hsa-miR-181a-5p are potential biomarkers associated with papillary thyroid cancer based on bioinformatics analysis.

BACKGROUND: The morbidity of thyroid carcinoma has been rising worldwide and increasing faster than any other cancer type. The most common subtype with the best prognosis is papillary thyroid cancer (PTC); however, the exact molecular pathogenesis of PTC is still not completely understood. METHODS: In the current study, 3 gene expression datasets (GSE3678, GSE3467, and GSE33630) and 2 miRNA expression datasets (GSE113629 and GSE73182) of PTC were selected from the Gene Expression Omnibus (GEO) database and were further used to identify differentially expressed genes (DEGs) and deregulated miRNAs between normal thyroid tissue samples and PTC samples. Then, Gene Ontology (GO) and pathway enrichment analyses were conducted, and a protein-protein interaction (PPI) network was constructed to explore the potential mechanism of PTC carcinogenesis. The hub gene detection was performed using the CentiScaPe v2.0 plugin, and significant modules were discovered using the MCODE plugin for Cytoscape. In addition, a miRNA-gene regulatory network in PTC was constructed using common deregulated miRNAs and DEGs. RESULTS: A total of 263 common DEGs and 12 common deregulated miRNAs were identified. Then, 6 significant KEGG pathways (P < 0.05) and 82 significant GO terms were found to be enriched, indicating that PTC was closely related to amino acid metabolism, development, immune system, and endocrine system. In addition, by constructing a PPI network and miRNA-gene regulatory network, we found that hsa-miR-181a-5p regulated the most DEGs, while BCL2 was targeted by the most miRNAs. CONCLUSIONS: The results of this study suggested that hsa-miR-181a-5p and BCL2 and their regulatory networks may play important roles in the pathogenesis of PTC.

Long non-coding RNA AFAP1-AS1/miR-320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance.

AFAP1-AS1 is a long non-coding RNA that is associated with tumorigenesis and poor prognosis in a variety of cancers. We have been suggested that AFAP1-AS1 increases tumorigenesis in laryngeal carcinoma specifically by enhancing stemness and chemoresistance. We assessed AFAP1-AS1 expression in human laryngeal specimens, paired adjacent normal tissues and human HEp-2 cells. Indeed, we found not only that AFAP1-AS1 was up-regulated in laryngeal carcinoma specimens and cells, but also that stemness-associated genes were overexpressed. Silencing of AFAP1-AS1 promoted HEp-2 cell chemoresistance under cisplatin treatment. Expression of AFAP1-AS1 was increased in drug-resistant Hep-2 cells. We then probed the mechanism of AFAP1-AS1 activity and determined that miR-320a was a potential molecular target of AFAP1-AS1. Luciferase reporter and qRT-PCR assays of AFAP1-AS1 and miR-320a levels in human specimens and cell cultures indicated that AFAP1-AS1 negatively regulates miR-320a. To discover the molecular mechanism of miR-320a, we again used the DIANA Tools algorithm to predict its genetic target, RBPJ. After cloning the 3'-untranslated regions (3'-UTR) of RBPJ into a luciferase reporter, we determined that miR-320a did in fact reduce RBPJ mRNA and protein levels. Ultimately, we determined that AFAP1-AS1 increases RBPJ expression by negatively regulating miR-320a and RBPJ overexpression rescues stemness and chemoresistance inhibited by AFAP1-AS1 silencing. Taken together, these results suggest that AFAP1-AS1 can serve as a prognostic biomarker in laryngeal carcinoma and that miR-320a has the potential to improve standard therapeutic approaches to the disease, especially for cases in which cancer cell stemness and drug resistance present significant barriers to effective treatment.

Effect of EphA7 Silencing on Proliferation, Invasion and Apoptosis in Human Laryngeal Cancer Cell Lines Hep-2 and AMC-HN-8.

AIMS: This study aimed to investigate the expression of EphA7 in human laryngeal squamous cell carcinoma (LSCC) tissues and disclose the potential roles and molecular mechanisms of EphA7 in LSCC. METHODS: In the present study, we examined EphA7 expression and its function and mechanism in LSCC. EphA7 expression levels were investigated by quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry in a panel of 35 LSCC patient cases. To investigate the potential mechanism of EphA7 in human laryngeal cancer, we employed EphA7 siRNA to knockdown EphA7 expression in LSCC cell line Hep-2 and AMC-HN-8. Subsequently, MTT, TUNEL, qRT-PCR, and western blotting were performed to disclose the roles of EphA7 on proliferation, invasion and migration, and apoptosis in LSCC cell line Hep-2 and AMC-HN-8. RESULTS: Depletion of EphA7 remarkably inhibited the proliferation and invasion of Hep-2 and AMC-HN-8 cells in comparison to control and EphA7 siRNA negative control (NC)-transfected cells. TUNEL staining assay demonstrated that, compared with the control group, the rate of apoptosis in the EphA7 siRNA group was significantly increased. In addition, knockdown of EphA7 in Hep-2 or AMC-HN-8 cells markedly decreased the expression of EphA7 and PTEN, which could contribute to apoptosis. However, the bpV(phen), a PTEN inhibitor, could attenuate anti-proliferation and pro-apoptotic effects of EphA7 siRNA in Hep-2 and AMC-HN-8 cells. CONCLUSION: Up-regulation of EphA7 was observed in human LSCC samples and down-regulation of EphA7 effectively suppressed laryngeal carcinoma cell growth and promoted its apoptosis. Thus, EphA7 has a critical role in modulating cell growth and apoptosis, which serves as a potential therapeutic target in human LSCC.

Krüppel-like factor 5: a novel biomarker for lymph node metastasis and recurrence in supraglottic squamous cell laryngeal carcinoma.

Krüppel-like factor 5 (KLF5), a zinc finger-containing transcription factor, is involved in important biological processes including cell transformation, proliferation, and carcinogenesis. However, its clinical significance has remained largely unknown in laryngeal cancer. Here, specimens from 144 patients with laryngeal tumors were investigated by immunohistochemical staining for KLF5, integrin-linked kinase (ILK), and E-cadherin expressions. A clinicopathological study revealed that the KLF5 expression level in tumor cells was significantly correlated with lymph node metastasis (P < 0.05) and local recurrence (P < 0.05). In addition, KLF5, ILK, and E-cadherin (epithelial-mesenchymal transition (EMT) biomarker) expressions were correlated with each other. These findings suggest that KLF5 may be an epithelial-mesenchymal transition-associated biomarker in human laryngeal carcinomas and play important roles in the progression of laryngeal carcinomas. KLF5 immunoreactivity is therefore considered a potential lymph node metastasis and recurrence factor in human laryngeal cancers. In addition, the KLF5-mediated pathway is a potential target for elimination of laryngeal cancer in the future.

Predictive factors for different subgroups of central lymph node metastasis in unilateral papillary thyroid carcinoma.

AIMS: We aimed to investigate the incidence rates and risk factors for different subgroups of central neck lymph node (LN) metastasis (prelaryngeal, ipsilateral paratracheal, pretracheal, and contralateral paratracheal) in unilateral papillary thyroid carcinoma (PTC) patients with clinically negative neck nodes (cN0). METHODS: We evaluated 184 patients from 2007 to 2009. The relationships between different subgroups of LN metastasis and clinical pathological factors were analyzed. RESULTS: The incidence rates of different central LN metastases were diverse. Multivariate analysis indicated that lymphovascular invasion, perithyroidal invasion, and tumor size were risk factors for ipsilateral paratracheal central LN metastasis; tumor size was an independent risk factor for pretracheal central LN metastasis, and pretracheal or/and ipsilateral paratracheal central LN metastasis were risk factors for contralateral paratracheal central LN metastasis. CONCLUSION: The extent of elective central LN dissection (CLND) should be decided based on different clinical pathological factors in cN0 PTC patients. Moreover, elective prelaryngeal CLND may be unnecessary.

Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma.

Head and neck cancer is a malignant tumour with a high mortality rate characterized by late diagnosis, high recurrence and metastasis rates, and poor prognosis. Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer. Various factors are involved in the occurrence and development of HNSCC, including external inflammatory stimuli and oncogenic viral infections. In recent years, studies on the regulation of cell death have provided new insights into the biology and therapeutic response of HNSCC, such as apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and recently the newly discovered cuproptosis. We explored how various cell deaths act as a unique defence mechanism against cancer emergence and how they can be exploited to inhibit tumorigenesis and progression, thus introducing regulatory cell death (RCD) as a novel strategy for tumour therapy. In contrast to accidental cell death, RCD is controlled by specific signal transduction pathways, including TP53 signalling, KRAS signalling, NOTCH signalling, hypoxia signalling, and metabolic reprogramming. In this review, we describe the molecular mechanisms of nonapoptotic RCD and its relationship to HNSCC and discuss the crosstalk between relevant signalling pathways in HNSCC cells. We also highlight novel approaches to tumour elimination through RCD.

TAGET: a toolkit for analyzing full-length transcripts from long-read sequencing.

Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for full-length transcriptome analysis. We present an integrated computational toolkit named TAGET for Iso-seq full-length transcript data analyses, including transcript alignment, annotation, gene fusion detection, and quantification analyses such as differential expression gene analysis and differential isoform usage analysis. We evaluate the performance of TAGET using a public Iso-seq dataset and newly sequenced Iso-seq datasets from tumor patients. TAGET gives significantly more precise novel splice site prediction and enables more accurate novel isoform and gene fusion discoveries, as validated by experimental validations and comparisons with RNA-seq data. We identify and experimentally validate a differential isoform usage gene ECM1, and further show that its isoform ECM1b may be a tumor-suppressor in laryngocarcinoma. Our results demonstrate that TAGET provides a valuable computational toolkit and can be applied to many full-length transcriptome studies.

Integrating DOI in T classification improves the predictive performance of laryngeal cancer staging.

It has been recognized that depth of invasion (DOI) is closely associated with patient survival for most types of cancer. The purpose of this study was to determine the DOI optimal cutoff value and its prognostic value in laryngeal squamous carcinoma (LSCC). Most importantly, we evaluated the prognostic performance of five candidate modified T-classification models in patients with LSCC. LSCC patients from Harbin Medical University Cancer Hospital and Chinese Academy of Medical Sciences Cancer Hospital were divided into training group (n = 412) and validation group (n = 147). The primary outcomes were overall survival (OS) and relapse-free survival (RFS), and the effect of DOI on prognosis was analyzed using a multivariable regression model. We identified the optimal model based on its simplicity, goodness of fit and Harrell's consistency index. Further independent testing was performed on the external validation queue. The nomograms was constructed to predict an individual's OS rate at one, three, and five years. In multivariate analysis, we found significant associations between DOI and OS (Depth of Medium-risk invasion HR, 2.631; P < .001. Depth of high-risk invasion: HR, 5.287; P < .001) and RFS (Depth of high-risk invasion: HR, 1.937; P = .016). Model 4 outperformed the American Joint Committee on Cancer (AJCC) staging system based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves. Inclusion of DOI in the current AJCC staging system can improve the differentiation of T classification in LSCC patients.

Emerging roles of platelets in cancer biology and their potential as therapeutic targets.

The main role of platelets is to control bleeding and repair vascular damage via thrombosis. They have also been implicated to promote tumor metastasis through platelet-tumor cell interactions. Platelet-tumor cell interactions promote tumor cell survival and dissemination in blood circulation. Tumor cells are known to induce platelet activation and alter platelet RNA profiles. Liquid biopsies based on tumor-educated platelet biomarkers can detect tumors and correlate with prognosis, personalized therapy, treatment monitoring, and recurrence prediction. Platelet-based strategies for cancer prevention and tumor-targeted therapy include developing drugs that target platelet receptors, interfere with the release of platelet particles, inhibit platelet-specific enzymes, and utilize platelet-derived "nano-platelets" as a targeted drug delivery platform for tumor therapy. This review elaborates on platelet-tumor cell interactions and the molecular mechanisms and discusses future research directions for platelet-based liquid biopsy techniques and platelet-targeted anti-tumor strategies.

[Construction and confirmation of a recombinant adenovirus vector of survivin].

OBJECTIVE: To construct a recombinant adenovirus of survivin vector and provid valuable reference for gene therapy of laryngeal cancer. METHODS: The survivin gene was cloned by PCR. After confirmation by enzyme restriction analysis and sequencing, the gene and the adenovirus vector were recombined together to construct the recombinant adenovirus vector. The recombinant adenovirus vector was confirmed via both sequencing and digestion restriction analysis, and then linearized and transfected into the HEK 293 cell line to generate recombinant adenovirus. RESULTS: The sequence analysis demonstrated that the survivin gene sequence was the same as published in the literature, suggesting that a recombinant adenovirus vector has been successfully constructed. CONCLUSIONS: A survivin recombinant adenovirus has been successfully constructed.

Interactive regulation of laryngeal cancer and neuroscience.

Nerve fibres are distributed throughout the body along with blood and lymphatic vessels. The intrinsic morphological characteristics of nerves and the general characteristics of secretions in the tumour microenvironment provide a solid theoretical basis for exploring how neuronal tissue can influence the progression of laryngeal cancer (LC). The central nervous system (CNS) and the peripheral nervous system (PNS) jointly control many aspects of cancer and have attracted widespread attention in the study of the progression, invasion and metastasis of tumour tissue banks. Stress activates the neuroendocrine response of the human hypothalamus-pituitary-adrenal (HPA) axis. LC cells induce nerve growth in the microenvironment by releasing neurotrophic factors (NTFs), and they can also stimulate neurite formation by secreting axons and axon guides. Conversely, nerve endings secrete factors that attract LC cells; this is known as perineural invasion (PNI) and promotes the progression of the associated cancer. In this paper, we summarize the systematic understanding of the role of neuroregulation in the LC tumour microenvironment (TME) and ways in which the TME accelerates nerve growth, which is closely related to the occurrence of LC.

LncRNA LINC-PINT Inhibits Malignant Behaviors of Laryngeal Squamous Cell Carcinoma Cells via Inhibiting ZEB1.

Objective: Laryngeal squamous cell carcinoma (LSCC) belongs to head and neck squamous cell carcinoma (HNSCC), with dismal prognosis. Here, this study aims to disclose the role of LINC-PINT in cancer development, which may contribute to improving the clinical outcomes of LSCC treatment. Methods: LINC-PINT expression in LSCC tissues and in TU-177 and Hep-2 cells was quantified, and subsequently, the association between LINC-PINT and LSCC malignancies was analyzed. pcDNA3.1-LINC-PINT or pcDNA3.1-EZH2 was introduced into Hep-2 and TU-177 cells. qRT-PCR and Western blot analyses examined the levels of proteins related to the AKT/mTOR pathway and their phosphorylated proteins in Hep-2 and TU-177 cells. The viability as well as migration and invasion abilities of Hep-2 and TU-177 cells were determined. Also, the distribution of LINC-PINT in Hep-2 cells was investigated as well as the interplay between LINC-PINT and EZH2. The downstream genes that might interact with EZH2 were screened. Results: LINC-PINT expression was inhibited in LSCC tissues and in Hep-2 and TU-177 cells, whose downregulation was associated with unsatisfactory prognosis. LINC-PINT overexpression suppressed the proliferative, migratory and invasive capacities of Hep-2 and TU-177 cells. LINC-PINT, mainly expressing in nuclei, could enrich EZH2 to silence ZEB1. In Hep-2 and TU-177 cells, the inhibition of LINC-PINT or overexpression of ZEB1 could enhance cell proliferation, migration and invasion. The phosphorylated levels of proteins related to the AKT/mTOR pathway were declined in cells with LINC-PINT overexpression, and the levels of these phosphorylated proteins were increased in cells with LINC-PINT inhibition. Conclusion: LINC-PINT enriches EZH2 to silence ZEB1 and thus inhibits the proliferative, migratory, and invasive capacities of Hep-2 and TU-177 cells. In addition, LINC-PINT might exert its biological function through the AKT/mTOR pathway.

Identification of Immune-Related LncRNA Pairs for Predicting Prognosis and Immunotherapeutic Response in Head and Neck Squamous Cell Carcinoma.

Long noncoding RNAs (lncRNAs) have multiple functions with regard to the cancer immunity response and the tumor microenvironment. The prognosis of head and neck squamous cell carcinoma (HNSCC) is still poor currently, and it may be effective to predict the clinical outcome and immunotherapeutic response of HNSCC by immunogenic analysis. Therefore, by using univariate COX analysis and Lasso Cox regression, we identified a signature consisting of 21 immune-related lncRNA pairs (IRLPs) that predicted clinical outcome and Immunotherapeutic response in HNSCC. Specifically, it was associated with immune cell infiltration (i.e., T cells CD4 memory resting, CD8 T cells, macrophages M0, M2, and NK cells), and more importantly this signature was strongly related with immune checkpoint inhibitors (ICIs) [such as PDCD1 (r = -0.35, P < 0.001), CTLA4 (r = -0.26, P < 0.001), LAG3 (r = -0.22, P < 0.001) and HAVCR2 (r = -0.2, P < 0.001)] and immunotherapy-related biomarkers (MMR and HLA). The present study highlighted the value of the 21 IRLPs signature as a predictor of prognosis and immunotherapeutic response in HNSCC.