Identification and validation of an immune-associated RNA-binding proteins signature to predict clinical outcomes and therapeutic responses in colon cancer patients.

BACKGROUND: The immune infiltration of patients with colon cancer (CC) is closely associated with RNA-binding proteins (RBPs). However, immune-associated RBPs (IARBPs) in CC remain unexplored. METHODS: The data were downloaded from The Cancer Genome Atlas (TCGA) and the patients were divided into four immune subgroups by single sample gene set enrichment analysis (ssGSEA), in which weighted gene correlation network analysis (WGCNA) identified modules of co-expressed genes correlated with immune infiltration. Univariate (UCR) and multivariate Cox regression (MCR) analyses were applied to screen survival-associated IARBPs. Then, a prognostic signature was performed on TCGA dataset. Risk model was constructed based on the TCGA dataset. Based on the median risk score, CC patients were subdivided into low- and high-risk groups. Furthermore, the accuracy and prognostic value of this signature were validated by using Kaplan-Meier (K-M) curve, receiver operating characteristic (ROC). We further validated the findings in Gene Expression Omnibus (GEO) database. Finally, we evaluated the association between gene expression level and drug sensitivity. RESULTS: Based on the infiltration of immune cells, the TCGA patients were divided into four subgroups. In total, we identified 25 IARBPs, after differential expression and WGCNA analysis. Subsequently, two IARBP signatures (FBXO17 and PPARGC1A) were identified to be significantly associated with the overall survival (OS) of CC patients. K-M survival analysis revealed that the low-risk group correlated with prolonged OS. The prognostic signature was an independent prognostic factor and reflects the immune status of CC patients. Finally, FBXO17 was related with drug sensitivity of bleomycin, gemcitabine, and lenvatinib. PPARGC1A was related to drug sensitivity of dabrafenib, vemurafenib, and trametinib. CONCLUSION: A novel two immune-associated RBPs that was established that may be useful in predicting survival and individualized treatment.

Identification and validation of the prognostic value of cyclic GMP-AMP synthase-stimulator of interferon (cGAS-STING) related genes in gastric cancer.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway play a significant role in the production of inflammatory cytokines and type I interferons. This study aims to develop a cGAS-STING pathway-related genes (CSRs) prediction model to predict prognosis in gastric cancer (GC). In the present study, we used The Cancer Genome Atlas (TCGA), Gene Expression Omnibus databases (GEO), CIBERSORT and Tumor Immune Estimation Resource databases (TIMER). The risk model based on five hub genes (IFNB1, IFNA4, IL6, NFKB2, and TRIM25) was constructed to predict the overall survival (OS) of GC. Further univariate Cox regression (URC) and multivariate Cox regression (MCR) analyses revealed that this risk scoring model was an independent factor. The results were verified by GEO external validation set. Multiple immune pathways were assessed by Gene Set Enrichment Analysis (GSEA). TIMER analysis demonstrated that risk score strongly correlated with Macrophage, B cells and CD8 + T cells infiltration. In addition, through 'CIBERSORT' package, the higher levels of infiltration of T cell follicular assistance (P = 0.011), NK cells-activated (P = 0.034), and Dendritic cells resting (P = 0.033) exhibited in high-risk group. Kaplan-Meier (K-M) survival analysis illustrated T cells CD4 memory resting and T cells follicular helper infiltration correlated with overall survival (OS) of GC patients in TCGA and GEO databases. Altogether, the risk score model can be conveniently used to predict prognosis. The immunocyte infiltration analysis provided a novel horizon for monitoring the status of the GC immune microenvironment.Abbreviations:TCGA: The Cancer Genome Atlas databases; GEO: Gene Expression Omnibus databases; GC: Gastric cancer; CSRs: cGAS-STING pathway-related genes; DECSRs: Differential expressed cGAS-STING pathway-related genes; PCSRs: Prognosis related cGAS-STING pathway genes; URC: Univariate Cox regression analyses; MCR: Multivariate Cox regression analyses GSEA: Gene set enrichment analysis; TIIC: Tumor-infiltrating immune cell.

Individualized Laparoscopic Therapy for Portal Hypertension: A Preliminary Single Center Experience.

BACKGROUND: To investigate the effects and technical points of several individualized laparoscopic therapies for patients suffering from cirrhotic portal hypertension. METHODS: In total, 385 cirrhotic patients who underwent the treatment of individualized laparoscopic therapy from February 2012 to December 2015 at the Clinical Medical College of Yangzhou University were enrolled in this study. We retrospectively analyzed the clinical data and the key technical points. RESULTS: Individualized laparoscopic therapies were successfully performed on 379 of 385 cases. Six cases were converted to a laparotomy (the rate of conversion to laparotomy was 1.6%). Modified laparoscopic splenectomy (MLS) for cirrhotic patients with hypersplenism was successfully performed on 103 of 105 cases. Laparoscopic azygoportal disconnection for cirrhotic patients with esophagogastric variceal bleeding (EGVB) or F3 varices was successfully performed on 61 of 62 cases, and modified laparoscopic splenectomy and azygoportal disconnection (MLSD) for cirrhotic patients with hypersplenism and EGVB or F3 varices was successfully performed on 196 of 201 cases. Synchronous MLS and laparoscopic partial hepatectomy (SLSH) for cirrhotic patients with hypersplenism and hepatocellular carcinoma (HCC) and synchronous MLSD and laparoscopic partial hepatectomy (SLSDH) for cirrhotic patients with hypersplenism, EGVB or F3 varices and HCC were all successfully implemented on 12 and 5 patients, respectively. From May 2013, we used the intraoperative autologous cell salvage during each individualized laparoscopic procedure. CONCLUSIONS: An individualized laparoscopic therapy was beneficial for different state of selected cirrhotic patients with portal hypertension with or without HCC.