Distinct from classical tumor angiogenesis, vasculogenic mimicry (VM) provides a blood supply for tumor cells independent of endothelial cells. VM has two distinct types, namely tubular type and ...patterned matrix type. VM is associated with high tumor grade, tumor progression, invasion, metastasis, and poor prognosis in patients with malignant tumors. Herein, we discuss the recent studies on the role of VM in tumor progression and the diverse mechanisms and signaling pathways that regulate VM in tumors. Furthermore, we also summarize the latest findings of non-coding RNAs, such as lncRNAs and miRNAs in VM formation. In addition, we review application of molecular imaging technologies in detection of VM in malignant tumors. Increasing evidence suggests that VM is significantly associated with poor overall survival in patients with malignant tumors and could be a potential therapeutic target.
Schematic illustration of the formation of the MWCNTs−COOH/UiO-66-NH2/MWCNTs−COOH/GCE and the high selectivity electrochemical sensing for detecting Cd2+ and Pb2+
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•An in situ growth ...method of UiO-66-NH2 was developed.•Three-layer assembly of MWCNTs-COOH/UiO-66-NH2/MWCNTs-COOH film was fabricated.•Potentiostatic electrodeposition is a unique driving force for thin film manufacturing.•These structures of the sensor reveal high selectivity towards Pb2+ and Cd2+.•Effective rapid and simultaneous quantitative detective of Pb2+ and Cd2+ in water.
In this work, an effective strategy for the fabrication of novel layer-by-layer multilayer films modified electrodes in electrochemical sensor applications. Glassy carbon electrode (GCE) surface has been modified with various multilayer films which were prepared by continuous repeated alternating electrodeposited of carboxylated multi-walled carbon nanotubes (MWCNTs−COOH) and Zr-metal-organic frameworks (UiO-66-NH2). Newly constructed three-layer assembly of MWCNTs−COOH/UiO-66-NH2/MWCNTs−COOH/GCE as voltammetric sensor was adapted to simultaneous detection Cd2+ and Pb2+ by square-wave anodic stripping voltammetry (SWASV). Meanwhile, the formation of MWCNTs−COOH/UiO-66-NH2/MWCNTs−COOH/GCE is supported by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), X-ray photoelectron spectra (XPS), X-ray diffraction patterns (XRD), and Fourier transform infrared spectra (FT-IR), which have been researched to estimate the effect of their electrochemical detection. Here, combined the abundant adsorption sites of UiO-66-NH2 with excellent conductivity ability of MWCNTs−COOH, and the dominant characteristics of the chelation mechanisms between amine groups and heavy metal cations, which strengthened its electrocatalytic activity. Results show that three-layer film modified GCE (MWCNTs−COOH/UiO-66-NH2/MWCNTs−COOH/GCE) can acquire the optimal simultaneous detection performances as the higher sensitivities to Cd2+ (0.2528 μA ppb−1) and Pb2+ (0.3012 μA ppb−1), the lower level detection limits to Cd2+ (0.090 ppb) and Pb2+ (0.071 ppb), as well as the superior linear relativity, respectively. Finally, excellent stability, repeatability and reproducibility of three-layer film modified GCE allow this sensing platform to work in practical application. The strategy that used layer by layer electrodeposition to assemble multilayer films will provide great potential for advanced applications in environment, biomedicine, human health and energy field.
Vasculogenic mimicry (VM) gives rise to tumor neovascularization that is critical for tumor growth and metastasis. Long non-coding RNAs (lncRNAs) have been implicated in diverse and fundamental ...biological processes. LINC00312 is associated with lung adenocarcinoma. In this study, we found that LINC00312 induced migration, invasion and VM of lung cancer cells by direct binding to the transcription factor Y-Box Binding Protein 1 (YBX1). Moreover, we demonstrated that YBX1 is associated with different fragments within 0-2410 nt 5'region of LINC00312. In addition, LINC00312 is associated with VM in 124 lung adenocarcinoma clinical specimens. The results suggest that LINC00312 is a promising therapeutic and diagnostic target for lung adenocarcinoma.
Deregulations of long non-coding RNAs (lncRNAs) have been implicated in cancer initiation and progression. Current methods can only capture differential expression of lncRNAs at the population level ...and ignore the heterogeneous expression of lncRNAs in individual patients.
We propose a method (LncRIndiv) to identify differentially expressed (DE) lncRNAs in individual cancer patients by exploiting the disrupted ordering of expression levels of lncRNAs in each disease sample in comparison with stable normal ordering. LncRIndiv was applied to lncRNA expression profiles of lung adenocarcinoma (LUAD). Based on the expression profile of LUAD individual-level DE lncRNAs, we used a forward selection procedure to identify prognostic signature for stage I-II LUAD patients without adjuvant therapy.
In both simulated data and real pair-wise cancer and normal sample data, LncRIndiv method showed good performance. Based on the individual-level DE lncRNAs, we developed a robust prognostic signature consisting of two lncRNA (C1orf132 and TMPO-AS1) for stage I-II LUAD patients without adjuvant therapy (P = 3.06 × 10
, log-rank test), which was confirmed in two independent datasets of GSE50081 (P = 1.82 × 10
, log-rank test) and GSE31210 (P = 7.43 × 10
, log-rank test) after adjusting other clinical factors such as smoking status and stages. Pathway analysis showed that TMPO-AS1 and C1orf132 could affect the prognosis of LUAD patients through regulating cell cycle and cell adhesion.
LncRIndiv can successfully detect DE lncRNAs in individuals and be applied to identify prognostic signature for LUAD patients.
We developed a miniaturized electrochemiluminescence (ECL) instrument coupled with a light‐emitting diode‐based bipolar electrochemical sensor (LED‐BPES). This instrument composes of a ...microcontroller circuit, a power supply circuit, a potentiostat, an optical detecting circuit, and a communication circuit. The multi‐pixel photon counter (MPPC), which is low‐cost, small‐size, and wide‐range in optical measurements, is chosen as the optical detector. The LED‐BPES composes of a disposable screen‐printed carbon electrode (SPCE) and a surface‐mount red LED. Depended on the closed bipolar electrode (C‐BPE) structure, the LED‐BPES not only avoids the employment of unstable and complex ECL reactions but also offers a cost‐effective alternative for the over‐priced ECL reagents by using a mini‐size commercial LED as the luminescent producer. The combination of MPPC and LED‐BPES helps to set up the simplified and downsized instrument system with low price and high efficiency. The presented instrument coupled with LED‐BPES works excellent in electroactive molecules detection and has great potential in the application of heavy metal ions detection.
Background The incidence and mortality of early-onset colorectal cancer (EOCRC; < 50 years old) is increasing worldwide, with a high recurrence rate. The inherent heterogeneity of EOCRC makes its ...treatment challenging. Hence, to further understand the biology and reveal the molecular mechanisms of EOCRC, a recurrence risk signature is needed to guide clinical management. Methods Based on the relative expression orderings (REOs) of genes in each sample, a prognostic signature was developed and validated utilizing multiple independent datasets. The underlying molecular mechanisms between distinct prognostic groups were explored via integrative analysis of multi-omics data. Results The prognostic signature consisting of 6 gene pairs (6-GPS) could predict the recurrence risk for EOCRC at the individual level. High-risk EOCRC classified by 6-GPS showed a poor prognosis but a good response to adjuvant chemotherapy. Moreover, high-risk EOCRC was characterized by epithelial-mesenchymal transition (EMT) and enriched angiogenesis, and had higher mutation burden, immune cell infiltration, and PD-1/PD-L1 expression. Furthermore, we identified four genes associated with relapse-free survival in EOCRC, including SERPINE1, PECAM1, CDH1, and ANXA1. They were consistently differentially expressed at the transcriptome and proteome levels between high-risk and low-risk EOCRCs. They were also involved in regulating cancer progression and immune microenvironment in EOCRC. Notably, the expression of SERPINE1 and ANXA1 positively correlated with M2-like macrophage infiltration. Conclusion Our results indicate that 6-GPS can robustly predict the recurrence risk of EOCRC, and that SERPINE1, PECAM1, CDH1, and ANXA1 may serve as potential therapeutic targets. This study provides valuable information for the precision treatment of EOCRC. Keywords: Early-onset colorectal cancer, Prognostic signature, Relative expression ordering, Recurrence-associated genes, Immune microenvironment
Abstract Our research endeavors are directed towards unraveling the stem cell characteristics of lower-grade glioma patients, with the ultimate goal of formulating personalized treatment strategies. ...We computed enrichment stemness scores and performed consensus clustering to categorize phenotypes. Subsequently, we constructed a prognostic risk model using weighted gene correlation network analysis (WGCNA), random survival forest regression analysis as well as full subset regression analysis. To validate the expression differences of key genes, we employed experimental methods such as quantitative Polymerase Chain Reaction (qPCR) and assessed cell line proliferation, migration, and invasion. Three subtypes were assigned to patients diagnosed with LGG. Notably, Cluster 2 (C2), exhibiting the poorest survival outcomes, manifested characteristics indicative of the subtype characterized by immunosuppression. This was marked by elevated levels of M1 macrophages, activated mast cells, along with higher immune and stromal scores. Four hub genes—CDCA8, ORC1, DLGAP5, and SMC4—were identified and validated through cell experiments and qPCR. Subsequently, these validated genes were utilized to construct a stemness risk signature. Which revealed that Lower-Grade Glioma (LGG) patients with lower scores were more inclined to demonstrate favorable responses to immune therapy. Our study illuminates the stemness characteristics of gliomas, which lays the foundation for developing therapeutic approaches targeting CSCs and enhancing the efficacy of current immunotherapies. By identifying the stemness subtype and its correlation with prognosis and TME patterns in glioma patients, we aim to advance the development of personalized treatments, enhancing the ability to predict and improve overall patient prognosis.
Cotton Verticillium wilt is mainly caused by the fungus
, which threatens the production of cotton. Its pathogen can survive in the soil for several years in the form of microsclerotia, making it a ...destructive soil-borne disease. The accurate, sensitive, and rapid detection of
from complex soil samples is of great significance for the early warning and management of cotton Verticillium wilt. In this study, we combined the loop-mediated isothermal amplification (LAMP) with CRISPR/Cas12a technology to develop an accurate, sensitive, and rapid detection method for
. Initially, LAMP primers and CRISPR RNA (crRNA) were designed based on a specific DNA sequence of
, which was validated using several closely related
spp. The lower detection limit of the LAMP-CRISPR/Cas12a combined with the fluorescent visualization detection system is approximately ~10 fg/μL genomic DNA per reaction. When combined with crude DNA-extraction methods, it is possible to detect as few as two microsclerotia per gram of soil, with the total detection process taking less than 90 min. Furthermore, to improve the method's user and field friendliness, the field detection results were visualized using lateral flow strips (LFS). The LAMP-CRISPR/Cas12a-LFS system has a lower detection limit of ~1 fg/μL genomic DNA of the
, and when combined with the field crude DNA-extraction method, it can detect as few as six microsclerotia per gram of soil, with the total detection process taking less than 2 h. In summary, this study expands the application of LAMP-CRISPR/Cas12a nucleic acid detection in
and will contribute to the development of field-deployable diagnostic productions.
Most of current gene expression signatures for cancer prognosis are based on risk scores, usually calculated as some summaries of expression levels of the signature genes, whose applications require ...presetting risk score thresholds and data normalization. In this study, we demonstrate the critical limitations of such type of signatures that the risk scores of samples will change greatly when they are normalized together with different samples, which would induce spurious risk classification and difficulty in clinical settings, and the risk scores of independent samples are incomparable if data normalization is not adopted. To overcome these limitations, we propose a rank-based method to extract a prognostic gene pair signature for overall survival of stage I non-small-cell lung cancer. The prognostic gene pair signature is verified in three integrated data sets detected by different laboratories with different microarray platforms. We conclude that, different from the type of signatures based on risk scores summarized from gene expression levels, the rank-based signatures could be robustly applied at the individualized level to independent clinical samples assessed in different laboratories.
Several studies have already identified the prognostic markers in colorectal cancer (CRC) based on somatic copy number alteration (SCNA). However, very little information is available regarding their ...value as a prognostic marker. Gene dosage effect is one important mechanism of copy number and dosage-sensitive genes are more likely to behave like driver genes. In this work, we propose a new pipeline to identify the dosage-sensitive prognostic genes in CRC. The RNAseq data, the somatic copy number of CRC from TCGA were assayed to screen out the SCNAs. Wilcoxon rank-sum test was used to identify the differentially expressed genes in alteration samples with |SCNA| > 0.3. Cox-regression was used to find the candidate prognostic genes. An iterative algorithm was built to identify the stable prognostic genes. Finally, the Pearson correlation coefficient was calculated between gene expression and SCNA as the dosage effect score. The cell line data from CCLE was used to test the consistency of the dosage effect. The differential co-expression network was built to discover their function in CRC. A total of six amplified genes (NDUFB4, WDR5B, IQCB1, KPNA1, GTF2E1, and SEC22A) were found to be associated with poor prognosis. They demonstrate a stable prognostic classification in more than 50% threshold of SCNA. The average dosage effect score was 0.5918 ± 0.066, 0.5978 ± 0.082 in TCGA and CCLE, respectively. They also show great stability in different data sets. In the differential co-expression network, these six genes have the top degree and are connected to the driver and tumor suppressor genes. Function enrichment analysis revealed that gene NDUFB4 and GTF2E1 affect cancer-related functions such as transmembrane transport and transformation factors. In conclusion, the pipeline for identifying the prognostic dosage-sensitive genes in CRC was proved to be stable and reliable.
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