Machine learning-based integration of CD8 T cell-related gene signatures for comprehensive prognostic assessment in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) stands as the most prevalent histological subtype of lung cancer, exhibiting heterogeneity in outcomes and diverse responses to therapy. CD8 T cells are consistently present throughout all stages of tumor development and play a pivotal role within the tumor microenvironment (TME). Our objective was to investigate the expression profiles of CD8 T cell marker genes, establish a prognostic risk model based on these genes in LUAD, and explore its relationship with immunotherapy response. Methods: By leveraging the expression data and clinical records from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts, we identified 23 consensus prognostic genes. Employing ten machine-learning algorithms, we generated 101 combinations, ultimately selecting the optimal algorithm to construct an artificial intelligence-derived prognostic signature named riskScore. This selection was based on the average concordance index (C-index) across three testing cohorts. Results: RiskScore emerged as an independent risk factor for overall survival (OS), progression-free interval (PFI), disease-free interval (DFI), and disease-specific survival (DSS) in LUAD. Notably, riskScore exhibited notably superior predictive accuracy compared to traditional clinical variables. Furthermore, we observed a positive correlation between the high-risk riskScore group and tumor-promoting biological functions, lower tumor mutational burden (TMB), lower neoantigen (NEO) load, and lower microsatellite instability (MSI) scores, as well as reduced immune cell infiltration and an increased probability of immune evasion within the TME. Of significance, the immunophenoscore (IPS) score displayed significant differences among risk subgroups, and riskScore effectively stratified patients in the IMvigor210 and GSE135222 immunotherapy cohort based on their survival outcomes. Additionally, we identified potential drugs that could target specific risk subgroups. Conclusions: In summary, riskScore demonstrates its potential as a robust and promising tool for guiding clinical management and tailoring individualized treatments for LUAD patients.

High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC. METHODS: This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18-70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0-42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003. FINDINGS: From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58-68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33-56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2-62·0]) than in the 45 Gy group (39·5 months [27·5-51·4]; hazard ratio 0·55 [95% CI 0·37-0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3-4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit. INTERPRETATION: Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18-70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option. FUNDING: Chinese Society of Clinical Oncology-Linghang Cancer Research, the Wu Jieping Medical Foundation, and Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital and Beijing Municipal Administration of Hospitals Incubating Program.

Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

Incidence Trends, Clinicopathologic Characteristics, and Overall Survival Prediction in Retinoblastoma Children: SEER Prognostic Nomogram Analysis.

BACKGROUND: Retinoblastoma is the most common intraocular malignant tumor occurring among children, with an incidence rate of 1/15 000. This study built a joinpoint regression model to assess the incidence trend of retinoblastoma from 2004 to 2015 and constructed a nomogram to predict the overall survival (OS) in children. MATERIALS AND METHODS: Patients less than 19 years diagnosed with retinoblastoma from 2004 to 2015 were selected from the SEER database. Joinpoint regression analysis (version 4.9.0.0) was performed to evaluate the trends in retinoblastoma incidence rates from 2004 to 2015. Cox Regression Analysis was applied to investigate prognostic risk factors that influence OS. RESULTS: Joinpoint regression revealed that retinoblastoma incidence exhibited no significant increase or decrease from 2004 to 2015. As per the multiple Cox regression, tumor size, laterality, and residence (rural-urban continuum code) were correlated with OS and were used to construct a nomogram. The nomogram exhibited a good C-index of 0.71 (95% CI, 0.63 to 0.79), and the calibration curve for survival probability demonstrated that the predictions corresponded well with actual observations. CONCLUSIONS AND RELEVANCE: A prognostic nomogram integrating the risk factors for retinoblastoma was constructed to provide comparatively accurate individual survival predictions. If validated, this type of assessment could be used to guide therapy in patients with retinoblastoma.

Induction immunochemotherapy followed by radiotherapy for patients with unresectable locally advanced or metastatic esophageal cancer: A propensity score-matched analysis.

BACKGROUND: The study aimed to investigate the efficacy of induction immunochemotherapy before radiotherapy (RT) for patients with locally advanced or metastatic esophageal cancer. METHODS: Patients with unresectable locally advanced or metastatic esophageal cancer who received induction immunochemotherapy followed by RT (ICIs + RT group) and RT alone (RT group) were retrospectively identified in two cancer centers, respectively. Propensity score matching (PSM) was used to balance the potential confounders between the two groups. Overall survival (OS), progression-free survival (PFS), and recurrence patterns were evaluated. RESULTS: A total of 467 patients were reviewed, and 66 were matched in each group. After PSM, the 1- and 2-year OS rates were 84.6% and 57.9% in ICIs + RT group, and 71.1% and 43.0% in RT group (HR 0.60, 95% CI 0.36-1.00, p = 0.050). The absolute increase of restricted mean survival time (RMST) for OS in ICIs + RT group compared with RT group were 0.89 years (p = 0.023) at one year and 2.59 years at two years (p = 0.030). The median PFS time, 1- and 2-year PFS rates were 20.3 months, 69.3%, and 45.7% in ICIs + RT group, and 12.2 months, 51.4%, and 35.8% in RT group (HR 0.64, 95% CI 0.41-0.99, p = 0.045). The cumulative locoregional recurrence (LRR) rate was significantly lower in ICIs + RT group (1-year rate, 17.4% vs. 38.8%, p = 0.011), and distant metastasis (DM) rates were comparable (p = 0.755). Consolidation ICIs was associated with a trend of improved 1-year OS and PFS. CONCLUSION: Induction immunochemotherapy followed by RT might improve locoregional control and survival outcomes for patients with unresectable locally advanced or metastatic esophageal cancer.

Neoadjuvant chemoradiotherapy followed by oesophagectomy may be the optimal treatment option for lower thoracic oesophageal cancer with supraclavicular lymph node metastasis: An inverse probability of treatment-weighted analysis of SEER database.

INTRODUCTION: Whether supraclavicular lymph node (SCLN) metastasis in patients with oesophageal cancer belongs to regional disease is controversial, leading to heterogeneity in clinical treatment decisions. This study aimed to determine the optimal treatment for lower thoracic oesophageal cancer (LTOC) with SCLN metastasis. METHODS: Patients with LTOC registered in the Surveillance, Epidemiology, and End Results database during 2010-2015 were identified. Selected patients were grouped according to disease spread as those with locoregional disease, with SCLN metastasis or with distant metastasis, as well as according to treatment modality (neoadjuvant chemoradiotherapy followed by surgery (nCRT+S group), upfront surgery ± adjuvant therapy (upfront S group) and definitive chemoradiotherapy (dCRT group)). The Cox regression analysis and inverse probability of treatment weighting (IPTW) were used to identify the optimal treatment modality for different groups. RESULTS: Of 11,767 LTOC patients identified from the database, the 5-year overall survival (OS) rates for patients with the locoregional disease (n = 7,541), SCLN metastasis (n = 120) and distant metastasis (n = 4,106) were 28.3%, 10.0% and 3.0%, respectively (P < 0.001). Among patients with SCLN metastasis, median OS in the nCRT+S, upfront S and dCRT groups were 25, 14 and 8 months, respectively (P < 0.001). After IPTW, the nCRT+S group was still associated with better median OS compared with other groups. The multivariate analysis identified treatment modality as an independent prognostic factor for OS. CONCLUSIONS: Neoadjuvant chemoradiotherapy followed by oesophagectomy may be the optimal treatment modality for LTOC with SCLN metastasis. The findings of this study need to be validated in large prospective studies.

First-line atezolizumab/durvalumab plus platinum-etoposide combined with radiotherapy in extensive-stage small-cell lung cancer.

BACKGROUND: Immunotherapy has made significant advances in the treatment of extensive-stage small-cell lung cancer (ES-SCLC), but data in combination with radiotherapy are scarce. This study aims to assess the safety and efficacy of chemoimmunotherapy combined with thoracic radiotherapy in patients with ES-SCLC. METHODS: This single-center retrospective study analyzed patients with ES-SCLC who received standard platinum-etoposide chemotherapy combined with atezolizumab or durvalumab immunotherapy as induction treatment, followed by consolidative thoracic radiotherapy (CTRT) before disease progression in the first-line setting. Adverse events during radiotherapy with or without maintenance immunotherapy and survival outcomes were assessed. RESULTS: Between December 2019 and November 2021, 36 patients with ES-SCLC were identified to have received such treatment modality at one hospital. The number of metastatic sites at diagnosis was 1-4. The biological effective dose of CTRT ranged from 52 to 113 Gy. Only two patients (6%) developed grade 3 toxic effect of thrombocytopenia, but none experienced grade 4 or 5 toxicity. Four patients developed immune-related pneumonitis during the induction treatment period but successfully completed later CTRT. The rate of radiation-related pneumonitis was 8% with grades 1-2 and well tolerated. The median progression-free survival (PFS) was 12.8 months, but the median overall survival (OS) was not determined. The estimated 1-year OS was 80.2% and 1-year PFS was 53.4%. CONCLUSIONS: Immunotherapy combined with CTRT for ES-SCLC is safe and has ample survival benefit.

Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens. The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated. AIM: To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients. METHODS: Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The edgeR, a Bioconductor package, was used to analyze mRNA expression between different groups. We screened genes specifically responsible for radioresistance to estimate overall survival. Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other. Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation of ßi and risk score using the following formula: . RESULTS: We identified three prognostic mRNAs (cathepsin S [CTSS], cluster of differentiation 180 [CD180], and SLP adapter and CSK-interacting membrane protein [SCIMP]) indicative of radioresistance. The expression of the three identified mRNAs was related to each other (r > 0.70 and P < 0.05). As to 1-year and 3-year overall survival prediction, the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841, respectively. When stratifying patients based on the risk score derived from the signature, the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group (P < 0.0001). Overall survival of the low-risk patients was significantly better than that of the high-risk patients (P = 0.018). CONCLUSION: We have developed a novel three-gene prognostic signature consisting of CTSS, CD180, and SCIMO for ESCC, which may facilitate the prediction of early prognosis of this malignancy.

MicroRNA-708 suppresses the proliferation, migration, and invasion of human retinoblastoma cells by targeting RAP2B, a member of the RAS oncogene family.

Retinoblastoma generally affects children and causes permanent vision failure or even death. MicroRNAs (miRs) have recently gained much attention during recent years. The miR-708 acts as a tumor suppressor in several human cancers, but the former has not been functionally characterized in human retinoblastoma. The present study was designed to investigate the role of miR-708 in human retinoblastoma. The results showed that miR-708 is significantly (P<0.05) downregulated in retinoblastoma cell lines. MiR-708 overexpression significantly (P<0.05) inhibited retinoblastoma cell growth and proliferation by inducing apoptosis. Furthermore, retinoblastoma cells overexpressing miR-708 exhibited a markedly lower migratory rate and invasiveness compared to negative control cells. The bioinformatics and dual luciferase assay revealed a RAS oncogene family protein, RAP2B, which acts as the regulatory target and functional mediator of the molecular role of miR-708 in retinoblastoma. Together, the present study revealed the tumor suppressor role of miR-708 and pointed to the therapeutic implications of miR-708/RAP2B in the treatment of retinoblastoma.

Anlotinib Hydrochloride and PD-1 Blockade as a Salvage Second-Line Treatment in Patients with Progress of Local Advanced Non-Small Cell Lung Cancer in Half a Year After Standard Treatment.

Purpose: As for local advanced non-small cell lung cancer (NSCLC), synchronous radiotherapy and chemotherapy is the standard treatment mode. But for patients with progress in half a year, which means the second-line chemotherapy effect is not ideal for them. We observed the efficacy and safety of anlotinib hydrochloride combined with PD-1 blockade as the second-line treatment for those patients in this trial. Patients and Methods: From January 2018 to December 2019, 57 patients with the progress of local advanced NSCLC treated with anlotinib plus PD-1 blockade until disease progression or intolerance as a result of adverse events. Patients have been assessed using computed tomography prior to treatment and during follow-up every 2 months until disease progression or death. The primary endpoint was objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS) and safety. Survival curves were created using the Kaplan-Meier method. Results: 57 patients were enrolled. The median age was 64 years, and 61.4% of the patients were men. The ORR was 50.9% with a median OS time of 14 months and the 1-year OS rates and PFS rates were 81.8% and 33.3%, respectively. The patients with squamous cell carcinoma, no brain or liver metastases had longer PFS than patients with liver metastasis. When the PFS was calculated from the time of second treatment, the median PFS was 9 months. Most adverse events (AEs) were grade 1-3, one drug-related death was noted. Conclusion: The expected outcome of this study is that anlotinib combined with PD-1 blockade has tolerable toxicity and better ORR, OS than second-line chemotherapy. The results may indicate additional treatment options for patients with progress of local advance NSCLC in half a year after standard treatment.

Prognostic role of an inflammation scoring system in radical resection of oral squamous cell carcinoma.

BACKGROUND: Inflammatory markers can influence the postoperative prognosis and outcome of malignant tumors. However, the role of inflammatory factors in oral squamous cell carcinoma (OSCC) are still debatable. The primary objective of this investigation was to detect the preoperative blood fibrinogen and neutrophil-lymphocyte ratio (NLR) in OSCC patients and to determine the predictive validity of F-NLR (combined fibrinogen and NLR score). METHODS: A total of 365 patients with oral cancer after surgery were separated into three classes: F-NLR of 2, with hyperfibrinogenemia (> 250 mg/dL) and high NLR (> 3.2); F-NLR of 1, with only one higher index; and F-NLR of 0, with no higher indices. Univariate and multivariate analyses were used to identify risk factors for the demographic and clinical characteristics of patients in the three F-NLR groups. Kaplan-Meier survival analysis was used to assess the prognosis. RESULTS: Preoperative F-NLR showed a relatively better predictive role in oral cancer prognosis than fibrinogen and NLR alone. Multivariate analysis revealed that F-NLR has the potential to be an independent predictor for OSCC cancer-specific survival (P < 0.001). Patients with high scores had a relatively poorer prognosis than those with low scores (P < 0.001). CONCLUSIONS: Our findings indicate that blood F-NLR may serve as an independent prognostic factor in OSCC patients.

The Tarantula Toxin ω-Avsp1a Specifically Inhibits Human CaV3.1 and CaV3.3 via the Extracellular S3-S4 Loop of the Domain 1 Voltage-Sensor.

Inhibition of T-type calcium channels (CaV3) prevents development of diseases related to cardiovascular and nerve systems. Further, knockout animal studies have revealed that some diseases are mediated by specific subtypes of CaV3. However, subtype-specific CaV3 inhibitors for therapeutic purposes or for studying the physiological roles of CaV3 subtypes are missing. To bridge this gap, we employed our spider venom library and uncovered that Avicularia spec. ("Amazonas Purple", Peru) tarantula venom inhibited specific T-type CaV channel subtypes. By using chromatographic and mass-spectrometric techniques, we isolated and sequenced the active toxin ω-Avsp1a, a C-terminally amidated 36 residue peptide with a molecular weight of 4224.91 Da, which comprised the major peak in the venom. Both native (4.1 µM) and synthetic ω-Avsp1a (10 µM) inhibited 90% of CaV3.1 and CaV3.3, but only 25% of CaV3.2 currents. In order to investigate the toxin binding site, we generated a range of chimeric channels from the less sensitive CaV3.2 and more sensitive CaV3.3. Our results suggest that domain-1 of CaV3.3 is important for the inhibitory effect of ω-Avsp1a on T-type calcium channels. Further studies revealed that a leucine of T-type calcium channels is crucial for the inhibitory effect of ω-Avsp1a.

Postoperative lymphatic recurrence distribution and delineation of the radiation field in lower thoracic squamous cell esophageal carcinomas: a real-world study.

BACKGROUND: To study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower thoracic squamous cell esophageal carcinomas. METHODS: We enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others. RESULTS: We enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%). CONCLUSIONS: According to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs.

Evaluation of a Novel Left Ventricular Assist Device for Resuscitation in an Animal Model of Ventricular Fibrillation Cardiac Arrest.

We evaluated an independently developed novel percutaneous implantable left ventricular assist device for resuscitation in a pig model of ventricular fibrillation cardiac arrest. The model was established in 10 domestic pigs by blocking the anterior descending coronary artery with a balloon after anesthesia. With ventilator-assisted ventilation, the independently developed percutaneous implantable left ventricular assist device was inserted via the femoral artery to assist circulation. According to whether effective circulatory support was achieved, the pigs were randomly divided into an experimental group and a control group. The experimental group was subjected to insertion of the assist device and received continuous circulatory support. The control group underwent insertion of the assist device; however, it did not start it within 15 minutes. For all animals, if successful rescue was achieved (sinus rhythm restoration within 15 minutes and maintenance for over 5 minutes), circulatory support was stopped, and the arterial blockage was removed. If sinus rhythm was not restored within 15 minutes, electric defibrillation, adrenaline injection, and removal of the arterial blockage were performed, and circulatory support was provided until sinus rhythm recovered. A determination of failed rescue was made when sinus rhythm was not restored after 1 hour. All successfully rescued animals were fed for 1 week. There were no significant differences in baseline data between the groups. All animals underwent successful novel left ventricular assist device implantation through the femoral artery. The rescue rate was significantly higher in the experimental group than in the control group (80% vs. 0%, [Formula: see text]). All successfully rescued animals survived after 1 week of feeding, and no eating or movement abnormalities were observed. We conclude that this independently developed percutaneous implantable left ventricular assist device can be conveniently and rapidly implanted through the femoral artery and can maintain basic circulatory perfusion during resuscitation in an animal model of cardiac arrest.

Testing lncRNAs signature as clinical stage-related prognostic markers in gastric cancer progression using TCGA database.

LncRNA expression can be conducive to gastric cancer (GC) prognosis. The objective of this study is to ascertain five specific lncRNAs involved in tumor progression of GC and their role as prognostic markers to diagnose clinical stage-wise GC. High-throughput RNA sequencing data were obtained from The Cancer Genome Atlas (TCGA) database and performed genome-wide lncRNA expression analysis using edgeR package, Bioconductor.org, and R-statistical computing to analyze differentially expressed lncRNA analysis. Cutoff parameters were FDR < 0.05 and |Log2FC| > 2. Total 351 tumor samples with differentially expressed lncRNAs were divided into group-1 lncRNAs such as AC019117.2 and LINC00941, and group-2 lncRNAs such as LINC02410, AC012317.2, and AC141273.1 by 2:1. The Spearman correlation coefficients (p < 0.05) and correlation test function (cor.test ()) were performed for lncRNAs as per clinical stage. Cytoscape software was used to construct lncRNA-mRNA interaction networks. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway (p < 0.05) analysis were conducted using the clusterProfiler package. Kaplan-Meier survival analysis was performed to determine the overall survival of patients based on the expression of five lncRNAs in different clinical stages of GC. AC019117.2 and LINC00941 of group 1 inferred a positive correlation with clinical stages of stage I to stage IV, and their expressions were higher in tumor tissues than normal tissues. On the contrary, LINC02410, AC012317.2, and AC141273.1 of group 2 exhibited a negative correlation with clinical stage, and they exhibited more expression in normal tissues compared to tumor tissues. GO and KEGG pathway analysis reported that AC019117.2 may interact with LINC00941 via ITGA3 and trophoblast glycoprotein (TPBG) to foster tumor progression. Tumor-specific group-1 lncRNAs were conducive to the poor overall survival and exhibited a positive correlation with the clinical stages of stage I to stage IV in GC as per the lncRNA-mRNA networking analysis. These five lncRNAs could be considered as clinically useful lncRNA-based prognostic markers to predict clinical stage-wise GC progression.

LINC00460 facilitated tongue squamous cell carcinoma progression via the miR-320b/IGF2BP3 axis.

OBJECTIVE: We aimed to explore the role of long intergenic non-protein coding RNA 460 (LINC00460) in tongue squamous cell carcinoma (TSCC). METHODS: We enrolled 27 TSCC patients to explore LINC00460 expression in clinical TSCC samples. RT-qPCR measured expression of molecules in this research. Loss-of-function assays explored biological function of LINC00460 in TSCC cells. RNA pull-down assay, luciferase reporter assay, and RIP assay investigated mechanism of LINC00460 underlying TSCC cells. RESULTS: TSCC tissues and cell lines both showed high expression of LINC00460. Functionally, LINC00460 downregulation inhibited TSCC cell growth and promoted TSCC cell apoptosis. Additionally, LINC00460 silencing suppressed tumor growth in vivo. Mechanistically, LINC00460 bound with microRNA 320b (miR-320b) in TSCC cells. MiR-320b overexpression suppressed TSCC cell growth and promoted TSCC cell apoptosis. Moreover miR-320b targeted insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) 3'untranslated region in TSCC cells. Furthermore, IGF2BP3 silencing suppressed TSCC cell growth and promoted TSCC cell apoptosis. IGF2BP3 upregulation countervailed effects of silenced LINC00460 on TSCC cells. The LINC00460/miR-320b/IGF2BP3 axis was associated with lymph node metastasis of TSCC patients. CONCLUSION: Our research illustrated that LINC00460 facilitated TSCC progression via the miR-320b/IGF2BP3 axis, highlighting a potential insight for the treatment of TSCC.

[Related factors of cervical lymph node metastasis and prognosis of patients with cN0 tongue squamous cell carcinoma].

PURPOSE: To explore the related factors of cervical lymph node metastasis and postoperative quality of life in patients with cN0 tongue squamous cell carcinoma (SCC), and provide a theoretical basis for clinical prediction of occult neck metastasis and improvement of survival rate. METHODS: A total of 283 patients with cN0 tongue SCC who underwent surgery in Huaian No.1 People's Hospital were collected. Chi-square test and logistic regression were used to analyze the correlation between cervical lymph node metastasis and clinical pathological parameters of patients. Single-factor and multi-factor Cox regression analysis were used to explore independent risk factors for prognosis of patients with tongue SCC. Survival analysis was used to study the correlation between cervical lymph node metastasis and prognosis of patients. SPSS 21.0 software package was used for statistical analysis. RESULTS: Chi-square test and logistic regression analysis showed that infiltration depth, T stage and pathological grade were closely related to cervical lymph node metastasis(P<0.05), and infiltration depth was the main factor leading to postoperative cervical lymph node metastasis(OR=2.175). The depth of invasion, pathological grade and cervical lymph node metastasis could be regarded as independent risk factor affecting the prognosis of patients with tongue SCC(P<0.05). CONCLUSIONS: Invasion depth, T stage and pathological grade can be used as indicators to predict occult cervical lymph node metastasis in patients with cN0 tongue SCC. Invasion depth, pathological grade and cervical lymph node metastasis can be used as independent indicators to predict the prognosis of patients with cN0 tongue SCC.

Circular RNA circCLK3 promotes the progression of tongue squamous cell carcinoma via miR-455-5p/PARVA axis.

A previous study has elucidated that circular RNA circCLK3 acts as an oncogenic gene in cervical cancer. However, the role and regulatory mechanism of circCLK3 in tongue squamous cell carcinoma (TSCC) remain unknown. Quantitative real-time PCR was used to examine targeted gene expression in different groups. Cell viability and proliferation were investigated by MTT and 5-ethynyl-2'-deoxyuridine assays. Cell migration and invasion were detected by Transwell assays, and cell apoptosis was measured by flow cytometry analysis. The interaction among genes was investigated using luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation assay. In the present study, our findings revealed the upregulated expression of circCLK3 in TSCC tissues and cell lines. CircCLK3 knockdown suppressed cell proliferation, migration invasion, and induced cell cycle arrest at G0/G1 phase in TSCC. Moreover, circCLK3 acted as a molecular sponge for miR-455-5p. PARVA was the target gene of miR-455-5p. Furthermore, the negative correlation between expression of miR-455-5p and circCLK3 or PARVA in TSCC tissues was discovered. Rescue assays indicated that PARVA overexpression reversed the circCLK3 knockdown-mediated inhibitory effects on the progression of TSCC. In summary, circCLK3 exerts its carcinogenic effects on TSCC progression via absorbing miR-455-5p to upregulate PARVA, which expands our knowledge on the underlying mechanism of TSCC.

Liquiritigenin exerts the anti-cancer role in oral cancer via inducing autophagy-related apoptosis through PI3K/AKT/mTOR pathway inhibition in vitro and in vivo.

Operative treatment on oral cancer greatly damages the chewing and language function of the patient, we aim to find better solution with fewer side effects. The anti-tumor effects of Liquiritigenin (LQ) have been explored in kinds of cancers, but not in oral cancer. In this study, our purpose is to reveal the effects of LQ on oral cancer and the associated mechanism.Cell proliferation was examined through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-Ethynyl-2'- deoxyuridine (EDU) staining. Cell apoptosis in cells and tissues were assessed by flow cytometry and terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Expressions of AKT and light chain 3 (LC3) were detected through Immunofluorescence. In addition, xenograft model was established by injecting the CAL-27 cells (2 × 106) subcutaneously into the right flanks of mice. Expression of Ki67 and Beclin1 in tissues was valued by Immunohistochemistry (IHC).We found that cell viability of CAL-27 and SCC-9 was effectively inhibited by LQ. Besides, obvious cell apoptosis and cell autophagy were induced by LQ. In addition, PI3K/AKT/mTOR pathway was sharply inactivated by LQ in oral cancer cells. Corresponding in vivo experiments demonstrated that tumor growth was largely restricted, cell apoptosis was augmented and autophagy was enhanced by LQ. What is more, phosphorylation of AKT in tumor tissues could also be inhibited by LQ. LQ inhibited the progression of oral cancer through inducing autophagy-associated apoptosis via PI3K/AKT/mTOR pathway inhibition, revealing a new possible scheme for the treatment of oral cancer.