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.

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.

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.

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.

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.

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.

Different Primary Sites of Hypopharyngeal Cancer Have Different Lymph Node Metastasis Patterns: A Retrospective Analysis From Multi-Center Data.

BACKGROUND: Most hypopharyngeal cancers (HPCs) develop lymph node metastasis (LNM) at initial diagnosis. Understanding the pattern of LNM in HPC could help both surgeons and radiologists make decisions in the management of cervical lymph nodes. METHODS: A total of 244 newly diagnosed HPC patients between January 2010 and December 2018 were recruited from three specialized cancer hospitals in mainland China. All patients received pre-treatment magnetic resonance imaging (MRI), and definitive radiotherapy with or without concurrent chemotherapy. We reassessed the features of the primary tumor (tumor size, primary location, and extent of invasion) and the involvement of lymph nodes at each level. According to the incidence of LNM, these levels were sequenced and sorted into drainage stations. Univariate and multivariate analyses were used to determine the risk factors for bilateral and regional lymph node metastasis. RESULTS: The cohort consisted of 195 piriform sinus cancers (PSC), 47 posterior wall cancers (PWC), and 2 post-cricoid cancers (PCC). A total of 176 patients (72.1%) presented with MRI-detectable LNMs. The overall LNM rates for level II-VI and retropharyngeal lymph nodes (RPLNs) were 59.0%, 52.9%, 14.3%, 1.6%, 2.9%, and 16.4%, respectively. Based on the prevalence of LNM at each level, we hypothesize that the lymphatic drainage of PSC was carried out in sequence along three stations: Level II and III (61.0% and 55.4%), Level IV and RPLN (15.9% and 11.3%), and Level V and VI (1.5% and 3.1%). For PWCs, lymphatic drainage is carried out at two stations: Level II, III, and RPLN (48.9%, 40.4%, and 34.0%) and Level IV-VI (6.4%, 0%, and 2.1%). According to univariate and multivariate analyses, posterior wall invasion was significantly correlated with bilateral LNM (P = 0.030, HR = 2.853 95%CI, 1.110-7.338) and RPLN metastasis (P = 0.017, HR = 2.880 95%CI, 1.209-6.862). However, pyriform sinus invasion was less likely to present with bilateral LNM (P = 0.027, HR = 0.311, 95%CI, 0.111-0.875) and RPLN metastasis (P = 0.028, HR = 0.346, 95%CI, 0.134-0.891). CONCLUSIONS AND RELEVANCE: The primary tumor site and extent of invasion are related to the pattern of lymph node metastasis. That is, the metastasis would drainage station by station along different directions.

Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.

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.

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.

Retropharyngeal Lymph Node Metastasis Diagnosed by Magnetic Resonance Imaging in Hypopharyngeal Carcinoma: A Retrospective Analysis From Chinese Multi-Center Data.

BACKGROUND: To assess the prevalence, risk factors and prognostic significance of retropharyngeal lymph node (RPLN) metastasis diagnosed by magnetic resonance imaging (MRI) in patients with hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: 259 patients from three cancer institutions in China from Jan 2010 to Dec 2018 were analyzed, retrospectively. All the patients had been given pre-treatment magnetic resonance imaging (MRI) of head and neck and were then treated with definitive radiotherapy with or without chemotherapy. Pretreatment diagnostic MRIs were reviewed by a dedicated head and neck radiologist, for the presence or absence of radiographically positive RPLN, cervical LN and tumor invasion.Demographic variables were analysed by descriptive statistics using SPSS 20.0. Predictors of the presence of RPLN and its prognostic significance were examined. RESULTS: RPLN metastasis was discovered in 44 patients (17%). Logistic analysis showed that posterior pharyngeal wall (PPW) primary tumor; PPW invasion; N2-3; multiple cervical lymph node (LN) involvement (>2 LNs) were associated with RPLN metastasis, with metastasis rates 37%, 30%, 31% and 33% respectively. Patients with RPLN metastasis had a significantly reduced 5-year overall survival (OS) and disease-free survival (DFS) compared to the non-RPLN metastasis group (OS 28% vs. 48%, p=0.001; DFS 25% vs. 41%, p=0.040). CONCLUSIONS: RPLN metastasis was not uncommon in HPSCC patients. Risk factors were: PPW primary tumor, PPW invasion and cervical LN status. RPLN metastasis is a poor prognosticator for survival.

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.

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.

Phototherapy together with it triggered immunological response for Anti-HPV treatment of oropharyngeal cancer: Removing tumor and pathogenic virus simultaneously.

Oropharyngeal squamous cell carcinoma (OPSCC) is one of most common cancers that often brings lots of inconvenience to the patient in swallowing and phonation even after the operation. Moreover, OPSCC is typically as nodal metastases and high recurrence rate due to the high-risk human papillomavirus (HPV) infection for 90% of patients. Obviously, completely curing OPSCC requires simultaneous removal of solid tumor and related pathogenic virus, which is very indispensable but never be realized by any kind of clinical therapy up to now. In this work, we selected the ZrC nanoparticles as difunctional photoactive substance for synchronous generation of hyperthermia and reactive oxygen species (ROS) under NIR excitation. The resultant synergistic photothermal and photodynamic treatment outcome contributed to an excellent anti-tumor effect. The phototherapy of this work was found not only to be able to damage cancer cells directly, but also could trigger the host immunity for further tumor removal and desirable HPV inactivation. An immunologic mechanism of this work was reasonable proposed by monitoring level of shock protein (HSP), calreticulin (CRT), T lymphocytes and dendritic cells (DCs) and immune check point of B7H3, B7H4 and PD-L1 post phototherapy. It was found that tumor-associated antigens of CRT ("eat-me" signal), HSPs and cell debris were released as cancer cell damage, and then the adaptive immune system and the congenital immunity were triggered to activate DCs maturity, antigen presentation to T cells, proliferation of CD4+ and CD8+ T cells, recruiting macrophages and NK cells and so forth immune responses. Being the first example of using phototherapy for virus-related cancer study, this work opens the door for photo-immunotherapy.

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.

The roles of extracellular vesicles in the development, microenvironment, anticancer drug resistance, and therapy of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the main malignant tumours affecting human health, mainly due to delayed diagnosis and high invasiveness. Extracellular vehicles (EVs) are membranous vesicles released by cells into the extracellular matrix that carry important signalling molecules and stably and widely exist in various body fluids, such as plasma, saliva, cerebrospinal fluid, breast milk, urine, semen, lymphatic fluid, synovial fluid, amniotic fluid, and sputum. EVs transport almost all types of bioactive molecules (DNA, mRNAs, microRNAs (miRNAs), proteins, metabolites, and even pharmacological compounds). These "cargoes" can act on recipient cells, reshaping the surrounding microenvironment and altering distant targets, ultimately affecting their biological behaviour. The extensive exploration of EVs has deepened our comprehensive understanding of HNSCC biology. In this review, we not only summarized the effect of HNSCC-derived EVs on the tumour microenvironment but also described the role of microenvironment-derived EVs in HNSCC and discussed how the "mutual dialogue" between the tumour and microenvironment mediates the growth, metastasis, angiogenesis, immune escape, and drug resistance of tumours. Finally, the clinical application of EVS in HNSCC was assessed.

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.

The Relationship Between Human Papillomavirus, OFD1 and Primary Ciliogenesis in the Progression of Oropharyngeal Cancer: A Retrospective Cohort Study.

PURPOSE: Infection with human papillomavirus (HPV) has been indicated to be a important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Primary ciliogenesis defects contribute to tumorigenesis, and OFD1 at centriolar satellites is a crucial suppressor of primary ciliogenesis. To identify novel markers associated with HPV-induced carcinogenesis, the interactions between HPV infection and primary ciliogenesis in the tumorigenesis and progression of OPSCC were investigated in this study. PATIENTS AND METHODS: The 1530 OPSCC patients recruited in this research were treated from 2000 to 2017. Immunohistochemistry and RT-PCR were performed on tissue samples to compare the expression of p16, TSLP, TGFß1, IFNγ, OFD1, and their relationship with clinical characteristics of patients. RESULTS: We speculate that the positive expression of p16 is related to early primary OPSCC, and the survival rate of p16 positive patients after radiotherapy and surgery is higher. Expression of TSLP on dendritic cells in HPV-positive OPSCC correlated with the expression of OFD1. HPV-positive OPSCC showed increased expression of OFD1 combined with reduced ciliogenesis. Hence, TSLP induced by HPV infection may reduce the invasive potential of OPSCC cells by promoting OFD1 expression, thereby inhibiting primary ciliogenesis. CONCLUSION: Our study demonstrated that HPV may be related to the progression of OPSCC by regulating OFD1 expression and primary ciliogenesis, making this protein a potential therapeutic target.

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.