Pathological scarring is a result of the hypertrophy of scar tissue during tissue repair following trauma. The aim of the present study was to assess the effect of ubiquitin-specific protease 4 (uSP4) silencing on pathological scarring, and to evaluate the mechanistic basis for the effect. an MTT assay was used to assess cell viability. immunoprecipitation (iP) was used to determine ubiquitination levels of the TGF-β receptor (Tβr)i and Smad7. Tumor formation was assessed by injecting keloid fibroblasts. Hematoxylin and eosin staining was used to detect pathological changes in tumor tissue. reverse transcription quantitative polymerase chain reaction and western blot analysis assays were used to evaluate the expression levels of Tβri and Smad7. compared with the untreated control animals, cell viability and the expression of Tβri and Smad7 increased significantly in animals treated with TGF-β. Short hairpin rna for uSP4 (shuSP4) decreased the cell viability of negative control cells, TGF-β-induced cellular proliferation, and the expression of TβRI and Smad7. IP experiments indicated that the ubiquitination level of Tβri was decreased following uSP4 silencing. There was no remarkable difference in the structure of scar tissue among the various animal groups at 14 days following treatment, while the necrotic area of the scar tissue in the shuSP4 and vialinin a (uSP inhibitor)-treated animals increased significantly at the 28th and 42nd day compared with the control animals. At days 14, 28 and 42, the expression levels of Tβri and Smad7 in the shuSP4 and vialinin a-treated animals were significantly decreased compared with the control animals (P<0.05). in summary, interference with or inhibition of uSP4 prevented the activity of the TGF-β/Smad pathway signaling and inhibited the formation of pathological scars.
Objectives
Our aim was to develop and validate a competing risk nomogram to determine the probability of cancer‐specific death in buccal mucosa cancer (BMC) patients.
Materials and Methods
We examined the records of BMC patients in the Surveillance, Epidemiology, and End Results (SEER) Program and First Affiliated Hospital of Nanchang University (China). We adopted the cumulative incidence function and Fine–Gray proportional hazards model based on univariate and multivariate analyses by R‐software to identify the risk factors associated with cancer‐specific death. Subsequently, a nomogram was developed and validated to predict the 3‐ and 5‐year probability of cancer‐specific death.
Results
In 1,286 BMC patients identified from SEER database, cumulative incidences of cancer‐specific death after diagnosis were 33.4% and 35.5% for 3 and 5 years, respectively. In the training cohort (n = 902) from SEER database, the Fine–Gray model indicated that age, Tumor Node Metastasis (TNM) stages, grade, surgery, and histological type were independent risk factors associated with cancer‐specific death, based on which a prognostic nomogram was developed. In the internal validation cohort from SEER database (n = 384) and the external validation cohort from our medical center (n = 174), the nomogram was well calibrated and showed remarkable prediction performance.
Conclusion
The nomogram created herein may prove to be a good assistant tool for assessing the prognosis of BMC patients.
Background and objectiveOral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck, and its morbidity and mortality are increasing year by year. Changes in key genes are thought to be closely related to the occurrence and development of OSCC. Pyroptosis is an inflammatory form of programmed cell death that has been implicated in malignancies and inflammatory diseases. Changes in the expression of long noncoding RNAs may also affect tumorigenesis and progression. In this study, our main objective was to evaluate the association between pyroptosis-related lncRNAs and prognosis in patients with OSCC.MethodsThe RNA-seq data and clinicopathological data of OSCC patients are from The Cancer Genome Atlas database. The pyroptosis gene set is obtained from Gene Set Enrichment Analysis database. Univariate COX, Lasso and multivariate COX regression analyses were used for the construction of risk prognostic models of OSCC, eight lncRNAs were incorporated into prognostic models. The Kaplan-Meier method and log-rank test were used to evaluate the differences of overall survival between patients in high-risk and low-risk groups. The reliability of predictions across the dataset was analyzed by receiver operating characteristic (ROC) curves. The immune signature score was calculated using the single-sample gene set enrichment analysis.ResultsEight pyroptosis-related lncRNAs were used to construct prognostic signature of OSCC, including AC136475.2, AC024075.2, JPX, ZFAS1, TNFRSF10A-AS1, LINC00847, AC099850.3 and IER3-AS1. According to this prognostic signature, patients with OSCC were divided into high-risk and low-risk groups. Kaplan-Meier survival analysis showed that the survival rate of the high-risk group was significantly lower than the low-risk group. ROC area for risk score was 0.716, and ROC area of the 8 lncRNAs are all between 0.5 and 1, implied that these lncRNAs had high accuracy in predicting the prognosis of OSCC patients. Immune Infiltration findings suggested that these lncRNAs affected immune responses in the microenvironment of OSCC.ConclusionThe prognostic signature based on pyroptosis-related lncRNAs potentially serves as an independent prognostic indicator for OSCC patients. And this signature facilitates research on targeted diagnosis and treatment of patients diagnosed with OSCC.
Melanoma is an invasive and malignant type of tumor with unsatisfactory therapeutic outcomes. The present study aimed to detect the expression levels of microRNA (miR)-125b in formalin-fixed paraffin-embedded (FFPE) melanoma tissues and the association of its expression levels with the clinical features, diagnosis and prognosis of melanoma. Expression levels of miR-125b in 29 FFPE melanoma specimens (16 primary and 13 metastatic tumors), and 16 intradermal nevus (IDN) specimens as a control, were detected by reverse transcription-quantitative PCR. Associations among miR-125b expression and mortality, patient age and sex, tumor location and size, lymph node metastasis (LNM) and TNM stage were analyzed by t-test. The diagnostic value of miR-125b for melanoma was evaluated by receiver operating characteristic (ROC) curve analysis. Prognosis of patients in the microRNA-125b low- and high-expression groups was analyzed by Fisher's exact test. The association between miR-125b expression and the overall survival of patients with melanoma was assessed using Kaplan-Meier curve analysis and a Cox proportional hazards model. The results revealed that the expression levels of miR-125b in primary and metastatic melanomas were significantly lower than those in the IDN control group (P<0.05), and the expression levels of miR-125b in the metastatic group were significantly lower than those in the primary group (P<0.05). In addition, the expression levels of miR-125b were significantly associated with LNM (P=0.001) and TNM stage (P=0.004), but not with age, sex, tumor size or location (P>0.05). ROC curve analysis revealed that the area under the curve (AUC) was 0.880, with a 95% CI of 0.777–0.984 (P<0.05). The overall survival rate of the patients with a low expression level of miR-125b (20.0%) was lower than that of patients with a high expression level of miR-125b (64.3%) (P<0.05). miR-125b expression was an independent predictor of overall survival in patients with melanoma [hazard ratio (HR), 0.252; 95% CI, 0.087–0.729]. Overall, these findings indicated that a low expression level of miR-125b was associated with higher LNM and TNM stage in patients with melanoma, and that this has a certain diagnostic value. miR-125b may be used for the early screening of melanoma and determining the prognosis of patients with melanoma, and may be a potential target for the treatment of the disease.
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