BackgroundEsophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The tumor microenvironment (TME) mainly comprises tumor cells and tumor-infiltrating immune cells mixed with stromal components. The latest research has displayed that tumor immune cell infiltration (ICI) is closely connected with the ESCC patients' clinical prognosis. This study was designed to construct a gene signature based on the ICI of ESCC to predict prognosis.MethodsBased on the selection criteria we set, the eligible ESCC cases from the GSE53625 and TCGA-ESCA datasets were chosen for the training cohort and the validation cohort, respectively. Unsupervised clustering detailed grouped ESCC cases of the training cohort based on the ICI profile. We determined the differential expression genes (DEGs) between the ICI clusters, and, subsequently, we adopted the univariate Cox analysis to recognize DEGs with prognostic potential. These screened DEGs underwent a Lasso regression, which then generated a gene signature. The harvested signature's predictive ability was further examined by the Kaplan-Meier analysis, Cox analysis, ROC, IAUC, and IBS. More importantly, we listed similar studies in the most recent year and compared theirs with ours. We performed the functional annotation, immune relevant signature correlation analysis, and immune infiltrating analysis to thoroughly understand the functional mechanism of the signature and the immune cells’ roles in the gene signature's predicting capacity.ResultsA sixteen-gene signature (ARSD, BCAT1, BIK, CLDN11, DLEU7-AS1, GGH, IGFBP2, LINC01037, LINC01446, LINC01497, M1AP, PCSK2, PCSK5, PPP2R2A, TIGD7, and TMSB4X) was generated from the Lasso model. We then confirmed the signature as having solid and stable prognostic capacity by several statistical methods. We revealed the superiority of our signature after comparing it to our predecessors, and the GSEA uncovered the specifically mechanism of action related to the gene signature. Two immune relevant signatures, including GZMA and LAG3 were identified associating with our signature. The immune-infiltrating analysis identified crucial roles of resting mast cells, which potentially support the sixteen-gene signature's prognosis ability.ConclusionsWe discovered a robust sixteen-gene signature that can accurately predict ESCC prognosis. The immune relevant signatures, GZMA and LAG3, and resting mast cells infiltrating were closely linked to the sixteen-gene signature's ability. 相似文献
Hyposmia, identified as reduced sensitivity to odor, is a common non-motor symptom of Parkinson’s disease (PD) that antedates the typical motor symptoms by several years. It occurs in ~90% of early-stage cases of PD. In addition to the high prevalence, the occurrence of hyposmia may also predict a higher risk of PD. Investigations into hyposmia and its relationship with PD may help elucidate the underlying pathogenic mechanisms. This review provides an update of olfactory dysfunction in PD and its potential as a biomarker for this devastating disease. 相似文献
To investigate if andrographolide impairs cholestatic liver injury. All rats were randomly divided into six groups—(1) control (n?=?6), (2) control?+?200 mg/kg andrographolide (n?=?6), (3) alpha-naphthylisothiocyanate (ANIT)-control (n?=?6), (4) ANIT?+?50 mg/kg andrographolide (n?=?6), (5) ANIT?+?100 mg/kg andrographolide (n?=?6), and (6) ANIT?+?200 mg/kg andrographolide (n?=?6). We gavaged 50 mg/kg ANIT to mimic cholestatic liver injury in rats. Seven days after treatment, all the rats were killed. Serum biochemistry and hepatic histopathological assays were performed to evaluate liver injury. We observed that 200 mg/kg andrographolide significantly decreased the level of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, total bilirubin, and total bile acid in the blood. It also markedly decreased hepatic interleukin-6 and tumor necrosis factor α. Furthermore, 200 mg/kg andrographolide significantly decreased malondialdehyde but increased superoxide dismutase, glutathione, and erythrocyte glutathione peroxidase. Moreover, 200 mg/kg andrographolide effectively increased the accumulation of sirtuin 1 and nuclear erythroid 2-related factor-2. It also attenuated the level of nuclear factor kappa-light-chain-enhancer of activated B and cyclooxygenase-2. These data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.