Serum peptidome profiling for the diagnosis of colorectal cancer: Discovery and validation in two independent cohorts

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were identified as candidate biomarkers for CRC. A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort. Peptide peaks at m/z 1895.3, 2020.9 and 3238.5 were identified as the partial sequences of complement component 4 (C4), complement component 3 (C3) and fibrinogen a chain (FGA), respectively. This study potentiated peptidomic analysis as a promising in vitro diagnostic tool for diagnosis of CRC. The identified peptides suggest the involvement of the C3, C4 and FGA in CRC pathogenesis

RANKL/RANK promotes the migration of gastric cancer cells by interacting with EGFR

BACKGROUND: The incidence and mortality rates of gastric cancer (GC) rank in top five among all malignant tumors. Chemokines and their receptor-signaling pathways reportedly play key roles in the metastasis of malignant tumor cells. Receptor activator of nuclear factor κB ligand (RANKL) is a member of the tumor necrosis factor family, with strong chemokine-like effects. Some studies have pointed out that the RANKL/RANK pathway is vital for the metastasis of cancer cells, but the specific mechanisms in GC remain poorly understood. RESULTS: This study reports original findings in cell culture models and in patients with GC. Flow cytometry and western blotting analyses showed that RANK was expressed in BGC-823 and SGC-7901 cells in particular. Chemotaxis experiments and wound healing assay suggested that RANKL spurred the migration of GC cells. This effect was offset by osteoprotegerin (OPG), a decoy receptor for RANKL. RANKL contributed to the activation of human epidermal growth factor receptor (HER) family pathways. The lipid raft core protein, caveolin 1 (Cav-1), interacted with both RANK and human epidermal growth factor receptor-1(EGFR). Knockdown of Cav-1 blocked the activation of EGFR and cell migration induced by RANKL. Moreover, RANK-positive GC patients who displayed higher levels of EGFR expression had poor overall survival. CONCLUSIONS: In summary, we confirmed that with the promotion of RANKL, RANK and EGFR can form complexes with the lipid raft core protein Cav-1, which together promote GC cell migration. The formation of the RANK-Cav-1-EGFR complex provides a novel mechanism for the metastasis of GC. These observations warrant confirmation in independent studies, in vitro and in vivo. They also inform future drug target discovery research and innovation in the treatment of GC progression

Online Hierarchical Sparse Representation of Multifeature for Robust Object Tracking

Object tracking based on sparse representation has given promising tracking results in recent years. However, the trackers under the framework of sparse representation always overemphasize the sparse representation and ignore the correlation of visual information. In addition, the sparse coding methods only encode the local region independently and ignore the spatial neighborhood information of the image. In this paper, we propose a robust tracking algorithm. Firstly, multiple complementary features are used to describe the object appearance; the appearance model of the tracked target is modeled by instantaneous and stable appearance features simultaneously. A two-stage sparse-coded method which takes the spatial neighborhood information of the image patch and the computation burden into consideration is used to compute the reconstructed object appearance. Then, the reliability of each tracker is measured by the tracking likelihood function of transient and reconstructed appearance models. Finally, the most reliable tracker is obtained by a well established particle filter framework; the training set and the template library are incrementally updated based on the current tracking results. Experiment results on different challenging video sequences show that the proposed algorithm performs well with superior tracking accuracy and robustness

Mesoporous InN/In2O3 heterojunction with improved sensitivity and selectivity for room temperature NO2 gas sensing

Establishing heterostructures is a good strategy to improve gas sensing performance, and has been studied extensively. In this work, mesoporous InN/In2O3 composite (InNOCs) heterostructures were prepared through a simple two-step strategy involving hydrothermal synthesis of In2O3 and subsequent nitriding into InN-composite In2O3 heterostructures. We found that the InN content has great influence on the resistance of InNOCs, and thus, the gas sensing performance. In particular, InNOC-36.9 (with InN content of 36.9% in the composites) shows an excellent sensing response towards different concentrations of NO2, as well as good stability after one week of exposure to 200 ppb NO2 at room temperature. The highest sensing response (Delta R/R-0) is up to 1.8 for the low NO2 concentration of 5 ppb. Even more significantly, the theoretical limit of detection (LOD) of the InNOC-36.9 sensor is 31.7 ppt based on a signal-to- noise ratio of 3 (the measured LOD is 5 ppb), which is far below the US NAAQS. value (NO2: 53 ppb). In addition, a rational band structure model combined with a surface reaction model is proposed to explain the sensing mechanism

Template-free synthesis of In2O3 nanoparticles and their acetone sensing properties

Ordered In2O3 nanoparticles (In2O3 NPs) were successfully prepared via a template-free method. The synthesis was conducted in a water-glycerol-ethylene glycol mixed solvent without any templates, and the ultra-fine nanostructured In2O3 has a uniform size of about 20-30 nm. The In2O3 nanoparticles exhibited improved sensitivity, fast response, and high selectivity to acetone. The enhanced acetone performance results from a large surface area with enough sensing active sites, and small particle size for effective electron depletion. (C) 2016 Elsevier B.V. All rights reserved

Identification of a novel prognostic signature correlated with epithelial‐mesenchymal transition, N6‐methyladenosine modification, and immune infiltration in colorectal cancer

Abstract Objective Colorectal cancer (CRC) is a commonly diagnosed human malignancy worldwide. Both epithelial‐mesenchymal transition (EMT) and N6‐methyladenosine (m6A) modification play a crucial role in CRC development. This study aimed to construct a prognostic signature based on the genes related to EMT and m6A modification. Method Firstly, the mRNA expression profiling of CRC tissues was analyzed using TCGA and GEO databases. The prognostic hub genes related to EMT and m6A modification were selected using weighted correlation network and cox regression analysis. The prognostic signature was constructed based on hub genes, followed by validation in three external cohorts. Finally, the expression of the representative hub gene was detected in clinical samples, and its biological role was investigated using assays in vivo and in vitro. Results A prognostic signature was constructed using the following genes: YAP1, FAM3C, NUBPL, GLO1, JARID2, NFKB1, CDKN1B, HOOK1, and GIPC2. The signature effectively stratified the clinical outcome of CRC patients in the training cohort and two validation cohorts. The subgroup analysis demonstrated the signature could identify high‐risk population from CRC patients within stage I‐II or III‐IV, female, male and elder patients. The signature was correlated with the infiltration of some immune cells (such as macrophage and regulatory T cells) and gene mutation counts. Finally, the hub gene GIPC2 was found to be downregulated in CRC tissues and most CRC cells lines. GIPC2 overexpression inhibited the malignant characteristics of CRC cells in vitro and in vivo through upregulating E‐cadherin and downregulating N‐cadherin, Vimentin, and Snail, while the opposite results were observed for GIPC2 knockdown in CRC cells. Conclusion Our present study for the first time constructed a novel prognostic signature related to EMT, m6A modification, and immune infiltration for CRC risk stratification. In addition, GIPC2 is identified as a promising clinical biomarker or therapeutical target for CRC