Integrated analysis of the lncRNA-miRNA-mRNA ceRNA network in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is particularly prevalent in East and Southeast Asia. Competing endogenous RNA (ceRNA) networks are known to play an essential role in the emergence of various diseases, including cancer. Building a network of protein-protein interactions (PPIs) and ceRNAs can facilitate the detection of potential connections between messenger RNAs (mRNAs) and various non-coding RNAs. However, the precise role of ceRNA networks in NPC has not been examined in detail. Therefore, the primary aim of the present study was to characterize a ceRNA network for NPC. Methods: Datasets of microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA microarrays were downloaded from the Gene Expression Omnibus (GEO) database. Data were standardized and differentially expressed genes (DEGs) were screened using the limma package. The ClusterProfiler software suite was used to perform enrichment analysis of differentially expressed mRNAs using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) techniques. Results: A total of 160 lncRNAs, 8 miRNAs, and 147 mRNAs were differentially expressed in NPC samples. A ceRNA network was constructed using four lncRNAs, five miRNAs, and one mRNA that were dysregulated in NPC. Cellular functions of the abnormally expressed mRNAs were mainly associated with tumor cell movement, cell growth and proliferation, cell cycle, invasion, and metastasis. Conclusions: The ceRNA network constructed herein clarified the regulatory mechanisms through which lncRNAs act as ceRNAs and participate in NPC development. Notably, lncRNAs, miRNAs, and mRNAs identified in this ceRNA network can serve as therapeutic targets and prognostic biomarkers for NPC.

The association between thyroid and breast cancers: a bidirectional mendelian randomization study.

Background: Thyroid and breast cancers are the two most frequent types of endocrine-related tumors among women worldwide, and their incidence is still on the rise. Observational studies have shown a relationship between thyroid and breast cancers. Nevertheless, many confounders predispose the results to interference. Accordingly, we performed a two-sample Mendelian randomization (MR) study to investigate the causal association between thyroid and breast cancers. Methods: We acquired breast cancer data from the UK Biobank (13,879 breast cancer cases and 198,523 controls) and the Breast Cancer Association Consortium (BCAC; 122,977 breast cancer cases and 105,974 controls), and thyroid cancer data from FinnGen Biobank (989 thyroid cancer and 217,803 controls). Then, the multiplicative random effects inverse variance weighting (IVW), weight median (WM), and MR Egger methods were executed for MR analysis. Results: Overall, IVW showed a causal effect of breast cancer on thyroid cancer using the BCAC dataset (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.036-1.322; P = 0.011), and this relationship was also supported by the UK Biobank dataset (OR = 23.899; 95% CI = 2.331-245.003; P = 0.007), which showed that breast cancer patients were more likely to be diagnosed with thyroid cancer. On the whole, the reverse MR analysis did not show a causal effect of breast cancer on thyroid cancer. However, IVW showed a causal effect of thyroid cancer on estrogen receptor -negative breast cancer using the BCAC dataset (OR = 1.019; 95% CI = 1.001-1.038; P = 0.043), which suggested that people with thyroid cancer were more likely to develop breast cancer. Conclusions: Breast cancer represents a possible risk factor for thyroid cancer and thyroid cancer also represents a possible risk factor for ER-negative breast cancer. Future studies using powerful genetic tools to determine the causal relationship between breast and thyroid cancers are required.

Development and validation of an MRI-based radiomic model for predicting overall survival in nasopharyngeal carcinoma patients with local residual tumors after intensity-modulated radiotherapy.

BACKGROUND: To investigate the potential value of the pretreatment MRI-based radiomic model in predicting the overall survival (OS) of nasopharyngeal carcinoma (NPC) patients with local residual tumors after intensity-modulated radiotherapy (IMRT). METHODS: A total of 218 consecutive nonmetastatic NPC patients with local residual tumors after IMRT [training cohort (n = 173) and validation cohort (n = 45)] were retrospectively included in this study. Clinical and MRI data were obtained. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomic features from pretreatment MRI. The clinical, radiomic, and combined models for predicting OS were constructed. The models' performances were evaluated using Harrell's concordance index (C-index), calibration curve, and decision curve analysis. RESULTS: The C-index of the radiomic model was higher than that of the clinical model, with the C-index of 0.788 (95% CI 0.724-0.852) versus 0.672 (95% CI 0.599-0.745) in the training cohort and 0.753 (95% CI 0.604-0.902) versus 0.634 (95% CI 0.593-0.675) in the validation cohort. Calibration curves showed good agreement between the radiomic model-predicted probability of 2- and 3-year OS and the actual observed probability in the training and validation groups. Decision curve analysis showed that the radiomic model had higher clinical usefulness than the clinical model. The discrimination of the combined model improved significantly in the training cohort (P < 0.01) but not in the validation cohort, with the C-index of 0.834 and 0.734, respectively. The radiomic model divided patients into high- and low-risk groups with a significant difference in OS in both the training and validation cohorts. CONCLUSIONS: Pretreatment MRI-based radiomic model may improve OS prediction in NPC patients with local residual tumors after IMRT and may assist in clinical decision-making.

Thalidomide attenuates oral epithelial cell apoptosis and pro-inflammatory cytokines secretion induced by radiotherapy via the miR-9-3p/NFATC2/NF-κB axis.

Oral mucositis is the most common oral complication of cancer patients receiving radiotherapy or chemotherapy, leading to poor quality of life. Increasing clinical studies demonstrated that thalidomide (THD) can effectively ameliorate radiation-induced oral mucositis (RIOM). Here we established an experimental mouse model, radiation-induced human oral epithelial cells (HOECs), and further investigate the underlying mechanism the THD protective effect against RIOM. Combined with RNA sequencing result, we selected the gene nuclear factor of activated T cells c2 (NFATC2) as the most interesting candidate. THD downregulated NFATC2 expression, attenuated human oral epithelial cells (HOECs) apoptosis and promoted pro-inflammatory factors secretion. Further studies show that overexpression of NFATC2 in HOECs promotes cells apoptosis and pro-inflammatory cytokines level, while inhibition of NFATC2 present an opposite effect. Additionally, the regulatory miRNA of NFATC2 was predicted using StarBase, and the targeting relationship between miR-9-3p and NFATC2 was confirmed using a dual-luciferase reporter gene assay. miR-9-3p mimic reversed the elevated cell apoptosis and pro-inflammatory cytokines level by radiation or NFATC2-overexpression. Furthermore, NFATC2 upregulated the phosphorylation of p65, thus activating the NF-κB pathway in RIOM; while miR-9-3p reduced this effect. In conclusion, THD attenuates oral epithelial cell apoptosis and pro-inflammatory cytokines secretion induced by radiotherapy via the miR-9-3p/NFATC2/NF- NF-κB axis.

Efficacy and safety of thalidomide in preventing oral mucositis in patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: A multicenter, open-label, randomized controlled trial.

BACKGROUND: This multicenter clinical trial was designed to evaluate the efficacy and safety of thalidomide (THD) in preventing oral mucositis (OM) in patients with nasopharyngeal carcinoma (NPC) undergoing concurrent chemoradiotherapy (CCRT). METHODS: Patients with locally advanced NPC were randomly assigned to either a THD group or a control group. All 160 patients received radical intensity-modulated radiotherapy plus cisplatin-based concurrent chemotherapy and basic oral hygiene guidance. Patients in the THD group received additional THD at the beginning of CCRT. The primary end points were the latency period and the incidence of OM. The secondary end points were mouth and throat soreness (MTS), weight loss, short-term efficacy, and adverse events. RESULTS: The median latency period of OM was 30 and 14 days in the THD and control groups, respectively (hazard ratio, 0.32; 95% confidence interval, 0.23-0.35; P < .0001). The incidence of OM and severe OM (World Health Organization grade 3 or higher) was significantly lower in the THD group than the control group (87.5% vs 97.5% [P = .016] and 27.5% vs 46.3% [P = .014], respectively). THD treatment also remarkably reduced the intensity of MTS and the degree of weight loss. In comparison with the control group, the incidence of nausea, vomiting, and insomnia was significantly decreased, whereas the incidence of dizziness and constipation was obviously increased in the THD group. The objective response rates 3 months after CCRT were similar between the groups. CONCLUSIONS: THD prolonged the latency period, reduced the incidence of OM, and did not affect the short-term efficacy of CCRT in patients with NPC. LAY SUMMARY: Oral mucositis is the most common complication of nasopharyngeal carcinoma during chemoradiotherapy; it decreases the patient's quality of life, and ideal mucosal protective agents are lacking. A few basic research and preclinical studies have shown that thalidomide may be an approach to ameliorating oral mucositis. The results of the current study confirm that thalidomide has a protective effect against oral mucositis in patients who have received chemoradiotherapy for nasopharyngeal carcinoma.

Identification of ferroptosis-related genes as potential biomarkers of tongue squamous cell carcinoma using an integrated bioinformatics approach.

Tongue squamous cell carcinoma (TSCC) is one of the deadliest cancers of the head and neck, but the role of the ferroptosis pathway in its development is still unknown. In this study we explored the pathogenetic mechanisms associated with ferroptosis in TSCC. We identified differentially expressed genes (DEGs) of TSCC patients and used gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) to annotate, visualize, and integrate these DEGs. Receiver operating characteristic curve (ROC) analysis was performed, and the STRING database was used to construct a protein-protein interaction network to evaluate the predictive value of ferroptosis-related DEGs. A total of 219 DEGs were identified and GO, KEGG, and GSEA showed that extracellular matrix (ECM)-receptor interaction and interleukin (IL)-17 signaling pathways were substantially upregulated in TSCC. Univariate Cox analysis revealed that high expression of CA9, TNFAIP3, and NRAS were predictive of a worse outcome. We then constructed a prognostic model that predicted survival in the validation cohort at 1 year and 32 months. Finally, 60 cases of tongue carcinoma and normal tissues were collected, and immunohistochemistry was used to detect the expression of CA9. We found that CA9 was strongly expressed in tongue carcinoma tissues and absent in adjacent tissues. Overall, we found that ferroptosis-related genes may affect TSCC prognosis through the ECM-receptor interaction and IL-17 signaling pathways. Additionally, immunohistochemistry confirmed that CA9 was highly expressed in tongue carcinoma tissues, and a model based on ferroptosis-related genes showed a good ability to predict overall survival in TSCC.

High SEC61G expression predicts poor prognosis in patients with Head and Neck Squamous Cell Carcinomas.

Background: Overexpression of the membrane protein SEC61 translocon gamma subunit (SEC61G) has been observed in a variety of cancers; however, its role in head and neck squamous cell carcinomas (HNSCC) is unknown. This study aimed to elucidate the relationship between SEC61G and HNSCC based on data from The Cancer Genome Atlas (TCGA) database. Methods: Data for HNSCC patients were collected from TCGA and the expression level of SEC61G was compared between paired HNSCC and normal tissues using the Wilcoxon rank-sum test. The relationship between clinicopathologic features and SEC61G expression was also analyzed using the Wilcoxon rank-sum test and logistic regression. Receiver operating characteristic (ROC) curves were generated to evaluate the value of SEC61G as a binary classifier using the area under the curve (AUC value). The association of clinicopathologic characteristics with prognosis in HNSCC patients was assessed using Cox regression and the Kaplan-Meier methods. A nomogram, based on Cox multivariate analysis, was used to predict the impact of SEC61G on prognosis. Functional enrichment analysis was performed to determine the hallmark pathways associated with differentially expressed genes in HNSCC patients exhibiting high and low SEC61G expression. Results: The expression of SEC61G was significantly elevated in HNSCC tissues compared to normal tissues (P < 0.001). The high expression of SEC61G was significantly correlated with the T stage, M stage, clinical stage, TP53 mutation status, PIK3CA mutation status, primary therapy outcome, and cervical lymph node dissection (all P < 0.05). Meanwhile, ROC curves suggested the significant diagnostic ability of SEC61G for HNSCC (AUC = 0.923). Kaplan-Meier survival analysis showed that patients with HNSCC characterized by high SEC61G expression had a poorer prognosis than patients with low SEC61G expression (hazard ratio = 1.95, 95% confidence interval 1.48-2.56, P < 0.001). Univariate and multivariate analyses revealed that SEC61G was independently associated with overall survival (P = 0.027). Functional annotations indicated that SEC61G is involved in pathways related to translation and regulation of SLITs/ROBOs expression, SRP-dependent co-translational protein targeting to the membrane, nonsense-mediated decay, oxidative phosphorylation, and Parkinson's disease. Conclusion: SEC61G plays a vital role in HNSCC progression and prognosis; it may, therefore, serve as an effective biomarker for the prediction of patient survival.

The efficacy of thalidomide on preventing and treating radiation-induced oral mucosi-tis in nasopharyngeal carcinoma / 中国肿瘤临床

Objective:To evaluate the efficacy and safety of thalidomide on preventing and treating radiation-induced oral mucositis (RIOM) in nasopharyngeal carcinoma (NPC). Methods:A total of 60 patients with NPC were randomly divided into treatment group and control group. The treatment group took thalidomide and gargled with mixture of saline+gentamycin+dexamethasone when ra-diotherapy started, and the control group gargled only with mixture of saline+gentamycin+dexamethasone. The time of occurrence and degree of RIOM in both groups were registered at the same time. Results:The incidence of RIOM in treatment group was lower than that in control group (P<0.05). For the incidence of 3 or 4 grade RIOM, the treatment group was also lower than the control group. No statistical difference in terms of objective response rate was found between the two groups (P>0.05). There was no statisti-cally significant difference between the treatment group and the control group in the oral average dose, V30, V35, V40, V45, V50, and V54 (P>0.05). There was no statistically significant difference between the treatment group and the control group in the use of nutri-tion agents, hormones and antibiotics (P>0.05). There was no statistical difference between the groups in the drowsiness, peripheral nerve toxicity, hematologic toxicity and gastrointestinal reaction (P>0.05). Conclusion:Thalidomide can reduce the incidence and se-verity of RIOM for radiotherapy of patients with NPC, which deserves clinic application.