Plasma Proteomics of Colorectal Cancer Based on DIA
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Qingsong Wang
PROVIDER: PXD065825 | iProX | Sun Jul 06 00:00:00 BST 2025
REPOSITORIES: iProX
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Project description:Colorectal cancer molecular signatures derived from omics data can be employed to stratify CRC patients and aid decisions about therapies or evaluate prognostic outcome. However, molecular biomarkers for identification of patients at increased risk of disease relapse are currently lacking. Here, we present a comprehensive multi-omics analysis of a Danish colorectal cancer tumor cohort composed of 412 biopsies from tumors of 371 patients diagnosed at TNM stage II or III. From mass spectrometry-based patient proteome profiles, we classified the tumors into four molecular subtypes, including a mesenchymal-like subtype. As the mesenchymal-rich tumors are known to represent the most invasive and metastatic phenotype, we focused on the protein signature defining this subtype to evaluate their potential as relapse risk markers. Among signature-specific proteins, we followed-up Caveolae-Associated Protein-1 (CAVIN1) and demonstrated its role in tumor progression in a 3D in vitro model of colorectal cancer. Compared to previous omics analyses of CRC, our multi-omics classification provided deeper insights into EMT in cancer cells with stronger correlations with risk of relapse.
2025-03-17 | PXD056331 | Pride
Project description:Globally, colorectal cancer(CRC) is the third most common malignancy. In recent years, despite the emergence of new screening and treatment strategies, the prognosis of CRC remains poor and distant metastasis remains a major obstacle to the treatment of CRC. Therefore, it is significant to explore new diagnostic and prognostic markers and therapeutic targets. Fibroblast growth factor 19(FGF19) has been reported to promote tumor invasion of CRC. However, the exact mechanism is still unclear.
2023-11-20 | GSE161963 | GEO
Project description:Matrix metalloproteinase-2 (MMP-2) plays a role in cell migration and invasion that involve degradation of extracellular matrix proteins as well as vascular remodeling. Increased expression of MMP-2 has often been observed in the tumors of colorectal cancer (CRC) patients. In order to unveil the perturbed proteomic signal during MMP-2-induced cancer progression, we analyzed MMP-2 dependent secretome change in HCT116 cancer cells by stable isotopic labeling with amino acids in cell culture (SILAC), together with the plasma proteome profile of CRC patients by label-free quantification according to disease progression from TNM stage I to IV. We also analyzed public database of CRC tissue proteome deposited by Clinical Proteomic Tumor Analysis Consortium (NCI/NIH). As a strategy for integrating the multi-layered proteomes, we first performed unsupervised hierarchical clustering on plasma and tissue proteomes according to TNM stage, and then Fisher’s exact test to find out which clusters were significantly represented by the secretome decreased by more than 1.5-fold upon MMP-2 knock down. The resultant cluster included CD9-ITGB1-ITGA7 protein complex as well as MMP-2. The proteins included in this cluster were mostly related to cell-cell communications and cell motility, and showed remarkable increased expression in tissue and plasma upon disease progression from TNM I to II. MMP-2 induced activation of FAK phospho-signaling in an activity-dependent manner. With the comparative and integrative multi-layered proteomic analysis, we suggest that high invasiveness featured in the disease progression of colorectal cancer with increased secretion of MMP-2 is because MMP-2 activates FAK signaling through CD9-integrin complex and consequently induces positive feedback of MMP-2 upregulation.
2021-08-26 | PXD018304 | Pride
Project description:Background & Aims. The current staging system for colorectal cancer (CRC) based on TNM classification allows prediction of potential recurrence. However, it does not necessarily make reliable personalized prediction of prognosis. In this paper we describe combination of clinicopathological data and gene signature of dissected tumor specimen with stage II and III CRC patients would improve the situation.. Methods. A total of 1978 CRC were collected over 5 years, and then 371 stage II and 322 stage III of them with more than 45.9 months records were subjected to clinicopathological feature analyses. Out of this collection, 129 stage II and III CRC cases were selected for analyses of gene expression profiles with resected specimen. The gene signatures were analyzed by repeated random divisions of the samples into training and test sets to extract discriminator genes. After testing the applicability of this discriminator set, it was subjected to validation using a newly obtained set of 69 samples. Results. The pathological factors in solo or in combinations could not make personalized recurrence prediction, except for partial success with stage II patients. The gene signature, on the other hand, was capable of producing a set of discriminator genes, though the accuracy was yet to be improved. We observed that the best result was obtained when discriminators were selected from stage II CRC samples and used for prognosis of stage II CRC. When stage III cases were included in the process of discriminator extraction or in the process to validate samples, the results were poorer. Finally, we examined 31 independent stage II samples with a set of 30 such discriminators and were able to obtain results with 78 % accuracy, 90 % negative predictive value (NPV), and 55% positive predictive value (PPV). Conclusions. Independent clinicopathological variables were not able to predict prognosis of individual patient, unless the factors are combined. On the other hand, gene signatures allowed accurate prediction of prognosis for individuals, especially with stage II CRC, suggesting its potential use for selection of best treatment option for individual patients. The accuracy of discriminator prediction will be further improved when we take the evolution of CRC into consideration. Of 198 samples, 129 represented the discovery phase and 69 represented the validation phase.
2009-07-02 | E-GEOD-12032 | biostudies-arrayexpress
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Project description:Mucinous adenocarcinoma (MuC), a subtype of colorectal cancer (CRC), exhibits distinct molecular features and a poorer prognosis compared to non-mucinous CRC (NMuC). Standard CRC treatments often fail to address MuC's unique characteristics, especially in stage II, where the benefit of adjuvant chemotherapy is unclear. Biomarkers that improve risk assessment and guide personalized treatment are needed. Based on RNA-seq data and Cox regression models, we developed a signature reflecting the characteristics of MuC which showed a strong prediction ability and clinical utility in both MuC and NMuC. Our signature represents a valuable tool for predicting recurrence and guiding personalized treatment in CRC.
2025-07-02 | GSE281917 | GEO
Project description:Determination of the profile of genes commonly aberrantly methylated in colorectal cancer (CRC) has substantial potential value for diagnostic and therapeutic application. However, our knowledge of the DNA methylation pattern in CRC is currently limited. Therefore, we analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in adjacent normal mucosa using beadchip array-based technology. We identified 621 CpG sites located in promoter region and CpG islands that were significantly hypermethylated in CRC compared to normal mucosa. Genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. In comparison with genome-wide expression array, mRNA expression was more like to be down-regulated in the genes demonstrating promoter hypermethylation, although this was not statistically significant. We validated 10 CpG sites that were shown to be hypermethylated in the array studies (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylaion (MAEL, SFT2D3) in CRC compared to normal mucosa using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data. In conclusion, we have shown that methylation profiling based on beadchip arrays is an effective method for screening for aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC. We measured the methylation status of the 27,578 CpG sites (Human Methylation27 DNA Analysis BeadChip) in 22 pairs of CRC tissue and adjacent normal mucosa to identify genes that are commonly aberrantly methylated in CRC.
2010-06-24 | E-GEOD-17648 | biostudies-arrayexpress
Project description:To identify new markers for colorectal cancer we scrutinized the methylation status by methyl-CpG immunoprecipitation followed by global methylation profiling on a CpG island microarray, as altered expression could drive genomic and chromosomal instability observed in these tumors. We show for the first time hypermethylation of MMP9, DNMT3A, and LIG4 in CRC which was confirmed in two independent ethnic CRC patients groups. Hypermethylation of the LIG4 promoter is a new mechanism to control ligase IV expression. It may represent a new epigenetic marker for colorectal cancer independent of known markers. Methylation profiling in 16 tumors of colorectal cancer patients compared to matched normal tissue of these patients
2013-12-31 | E-GEOD-47413 | biostudies-arrayexpress
Project description:microRNA profile of TNM-specific sequence design and integrated network-based bioinformatic analysis in 20 Colorectal cancer patients(n=5 for each TNM stage) are carried out to find the dynamic miRNA expression pattern specific to TNM stage. Gene microrray experiment of the same samples were also performed. Two different platform of microarray data were analyzed together to uncover the potential biomarker for progression of colorectal cancer.
2015-09-30 | GSE41012 | GEO
Project description:Global gene profile of TNM-specific sequence design and integrated network-based bioinformatic analysis in 20 Colorectal cancer patients(n=5 for each TNM stage) are carried out to find the dynamic gene expression pattern specific to TNM stage. microRNA microrray experiment of the same samples were also performed. Two different platform of microarray data were analyzed together to uncover the potential biomarker for progression of colorectal cancer.
2015-09-30 | GSE41011 | GEO