ABSTRACT
To precisely predict the clinical outcome and determine the optimal treatment options for patients with esophageal squamous cell carcinoma (ESCC) remains challenging. Prognostic models based on multiple molecular markers of tumors have been shown to have superiority over the use of single biomarkers. Our previous studies have identified the crucial role of ezrin in ESCC progression, which prompted us to hypothesize that ezrin-associated proteins contribute to the pathobiology of ESCC. Herein, we explored the clinical value of a molecular model constructed based on ezrin-associated proteins in ESCC patients. We revealed that the ezrin-associated proteins (MYC, PDIA3, and ITGA5B1) correlated with the overall survival (OS) and disease-free survival (DFS) of patients with ESCC. High expression of MYC was associated with advanced pTNM-stage (P=0.011), and PDIA3 and ITGA5B1 were correlated with both lymph node metastasis (PDIA3: P < 0.001; ITGA5B1: P=0.001) and pTNM-stage (PDIA3: P=0.001; ITGA5B1: P=0.009). Furthermore, we found that, compared with the current TNM staging system, the molecular model elicited from the expression of MYC, PDIA3, and ITGA5B1 shows higher accuracy in predicting OS (P < 0.001) or DFS (P < 0.001) in ESCC patients. Moreover, ROC and regression analysis demonstrated that this model was an independent predictor for OS and DFS, which could also help determine a subgroup of ESCC patients that may benefit from chemoradiotherapy. In conclusion, our study has identified a novel molecular prognosis model, which may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for ESCC treatment.
Subject(s)
Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/genetics , Models, Genetic , Biomarkers, Tumor/genetics , Esophageal Squamous Cell Carcinoma/diagnosis , Esophageal Squamous Cell Carcinoma/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Predictive Value of Tests , PrognosisABSTRACT
BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers worldwide. Treatment of ESCC is in progress through accurate staging and risk assessment of patients. The emergence of potential molecular markers inspired us to construct novel staging systems with better accuracy by incorporating molecular markers. METHODS: We measured H scores of 23 protein markers and analysed eight clinical factors of 77 ESCC patients in a training set, from which we identified an optimal MASAN (MYC, ANO1, SLC52A3, Age and N-stage) signature. We constructed MASAN models using Cox PH models, and created MASAN-staging systems based on k-means clustering and minimum-distance classifier. MASAN was validated in a test set (n = 77) and an independent validation set (n = 150). RESULTS: MASAN possessed high predictive accuracies and stratified ESCC patients into three prognostic groups that were more accurate than the current pTNM-staging system for both overall survival and disease-free survival. To facilitate clinical utilisation, we also constructed MASAN-SI staging systems based on staining indices (SI) of protein markers, which possessed similar prognostic performance as MASAN. CONCLUSION: MASAN provides a good alternative staging system for ESCC prognosis with a high precision using a simple model.
Subject(s)
Anoctamin-1/metabolism , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Membrane Transport Proteins/metabolism , Neoplasm Proteins/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Age Factors , Algorithms , Biomarkers, Tumor/metabolism , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/metabolism , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Sensitivity and Specificity , Survival Analysis , Tissue Array AnalysisABSTRACT
Phimosis and redundant prepuce, as common problems in andrology, are found in the majority of male neonates. Early treatment of neonatal phimosis and redundant prepuce has the advantages of better cost--effectiveness and higher safety, and contributes much to the prevention of childhood urinary tract infection and adult sexually transmitted diseases, as well as to the improvement of genital hygiene. Neonatal circumcision is commonly performed in some countries, but remains at a low rate in China. This article updates surgical and non-surgical treatments of neonatal phimosis and redundant prepuce, introduces the benefits of neonatal circumcision, and appeals for more attention to the management of neonatal phimosis and redundant prepuce.
Subject(s)
Circumcision, Male/methods , Phimosis/surgery , Phimosis/therapy , Child, Preschool , Humans , Infant , MaleABSTRACT
Recent randomized controlled clinical trials in Africa have demonstrated that adult male circumcision (MC) efficiently decreases the rate of HIV, HPV and HSV-2 infections. Many studies have clearly shown that MC is a simple, safe, and cost-effective method for the prevention of sexually transmitted diseases and urinary tract infection, and for improving genital hygiene. While a 30% MC prevalence exists worldwide, only 5% or less of the Chinese males have undergone circumcision. In this review, we report recent trends in international MC and HIV prevention efforts, as well as the potential benefits and importance of promoting MC in China. We appeal to medical and public health authorities to pay close attention to the international experience in MC and HIV prevention.
