ABSTRACT
BACKGROUND: Stomach adenocarcinomas (STAD) are the most common malignancy of the human digestive system and represent the fourth leading cause of cancer-related deaths. As early-stage STAD are generally mild or asymptomatic, patients with advanced STAD have short overall survival. Early diagnosis of STAD has a considerable influence on clinical outcomes. METHODS: The mRNA expression data and clinical indicators of STAD and normal tissues were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The gene expression differences were analyzed by R packages, and gene function enrichment analysis was performed. Kaplan-Meier method and univariate Cox proportional risk regression analysis were used to screen differential expressed genes (DEGs) related to survival of STAD patients. Multivariate Cox proportional risk regression analysis was used to further screen and determine the prognostic DEGs in STAD patients, and to construct a multigene prognostic prediction signature. The accuracy of predictive signature was tested by receiver operating characteristic (ROC) curve software package, and the nomogram of patients with STAD was drawn. Cox regression was used to investigate the correlation between multigene prognostic signature and clinical factors. The predictive performance of this model was compared with two other models proposed in previous studies using KM survival analysis, ROC curve analysis, Harrell consistency index and decision curve analysis (DCA). qRT-PCR and Western blot were used to verify the expression levels of prognostic genes. The pathways and functions of possible involvement of features were predicted using the GSEA method. RESULTS: A total of 569 early-stage specific DEGs were retrieved from TCGA-STAD dataset, including 229 up-regulated genes and 340 down-regulated genes. Enrichment analysis showed that the early-stage specific DEGs were associated with cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and calcium signaling pathway. Multiple Cox regression algorithm was used to identify 10 early-stage specific DEGs associated with overall survival (P < 0.01) of STAD patients, and a multi-mRNA prognosis signature was established. The patients were divided into high-risk group and low-risk group according to the risk score. In the training set, the prognostic signature was positively correlated with tumor size and stage (P < 0.05), survival curve (P < 0.001) and time-dependent ROC (AUC = 0.625). In the training dataset and test dataset, the both signatures had good predictive efficiencies. Cox regression and DCA analysis revealed that the prognostic signature was an independent factor and had a better predict effect than the conventional TNM stage classification method and the earlier published biomarkers on the prognosis of STAD patients. CONCLUSION: In this study, based on the early-stage specifically expressed genes, the prognostic signature constructed through TCGA and GEO datasets may become an indicator for clinical prognosis assessment of STAD and a new strategy for targeted therapy in the future.
Subject(s)
Adenocarcinoma , Biomarkers, Tumor , Stomach Neoplasms , Humans , Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cytokines , Ligands , Prognosis , Receptors, Cytokine , RNA, Messenger/genetics , Stomach/pathology , Stomach Neoplasms/geneticsABSTRACT
Analysis of the Surveillance, Epidemiology and End Results (SEER) registry indicates that more than 20% of all cancers are located in the gastrointestinal (GI) tract. Although colon adenocarcinomas constitute approximately 90% of all malignant intestinal neoplasia, the remaining 10% of tumors in the small intestine (SI), appendix and colon are clinically relevant since their late presentation due to a paucity of overt symptoms culminates in a high mortality rate despite the fact that many such lesions are not intrinsically aggressive neoplasia. Thus, neuroendocrine tumors (NETs), adenocarcinomas (except for colonic), lymphomas, sarcomas and GI stromal tumors (GISTs) of the SI, appendix and colon, while relatively rare, represent an under-recognized and underserved group of lesions. According to the SEER registry 1973-2004, the incidence/100,000 of sarcomas has remained unchanged, while NETs, adenocarcinomas (except colon), and lymphomas have increased 2.9-, 1.6-, and 2.0-fold, respectively. This may, at least partly, reflect the development of more sophisticated diagnostic techniques including high resolution CT and MRI, capsule endoscopy and somatostatin scintigraphy for NETs. Although the development of specific targeted therapies such as tyrosine kinase inhibitors (TKIs) for GISTs and somatostatin analogs for NETs have improved prognosis, early detection remains the critical variable in determining outcome. The overall 5-year survival rates have remained relatively unchanged over time (1973-1999), or are only improved marginally for some subgroups. We present an overview of the epidemiology of these uncommon cancers, and address their clinical behavior, and current diagnostic and therapeutic options.
Subject(s)
Appendiceal Neoplasms/epidemiology , Colonic Neoplasms/epidemiology , Intestinal Neoplasms/epidemiology , Intestine, Small/pathology , Adenocarcinoma/epidemiology , Appendiceal Neoplasms/pathology , Appendiceal Neoplasms/therapy , Colonic Neoplasms/pathology , Colonic Neoplasms/therapy , Gastrointestinal Stromal Tumors/epidemiology , Humans , Intestinal Neoplasms/pathology , Intestinal Neoplasms/therapy , Lymphoma/epidemiology , Neuroendocrine Tumors/epidemiology , SEER Program , Sarcoma/epidemiology , Survival Analysis , Time Factors , Treatment Outcome , United States/epidemiologyABSTRACT
AIM: Hepatic cavernous hemangioma (HCH) is the most common benign tumor of the liver and its management is still controversial. Recent success in situ radiofrequency ablation of hepatic malignancies has led us to consider using this technique in patients with HCH. This study was to assess the efficacy, safety, and complications of percutaneous radiofrequency ablation (PRFA) under ultrasonography guidance in patients with HCH. METHODS: Twelve patients (four men and eight women, age ranged 33-56 years, mean age was 41.7 years) with 15 hepatic cavernous hemangiomas (2.5 cm to 9.5 cm) were treated using the RF-2000 generator and 10-needle LeVeen electrode percutaneously guided by B-ultrasound. Lesions larger than 3 cm were treated by multiple overlapping ablations that encompass the entire lesion as well as a rim of normal liver tissue (approximately 0.5 cm). RESULTS: All the patients who received PRFA therapy had no severe pain, bleeding or bile leakage during and after the procedures. Nine to 34 months' follow-up (mean, 21 months) by ultrasound and/or spiral CT scan demonstrated that the ablated lesions in this group were shrunk remarkably, and the shrunken range was 38-79 % (mean, 67 % per 21 months). The contrast enhancement was disappeared within the tumor or at its periphery in all cases on spiral CT scans obtained 3 to 6 months after treatment. CONCLUSION: The results of this study suggest that PRFA therapy is a mini-invasive, simple, safe, and effective method for the treatment of selected patients with HCH.