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Large scale systematic proteomic quantification from non-metastatic to metastatic colorectal cancer.

ABSTRACT: A systematic proteomic quantification of formalin-fixed, paraffin-embedded (FFPE) colorectal cancer tissues from stage I to stage IIIC was performed in large scale. 1017 proteins were identified with 338 proteins in quantitative changes by label free method, while 341 proteins were quantified with significant expression changes among 6294 proteins by iTRAQ method. We found that proteins related to migration expression increased and those for binding and adherent decreased during the colorectal cancer development according to the gene ontology (GO) annotation and ingenuity pathway analysis (IPA). The integrin alpha 5 (ITA5) in integrin family was focused, which was consistent with the metastasis related pathway. The expression level of ITA5 decreased in metastasis tissues and the result has been further verified by Western blotting. Another two cell migration related proteins vitronectin (VTN) and actin-related protein (ARP3) were also proved to be up-regulated by both mass spectrometry (MS) based quantification results and Western blotting. Up to now, our result shows one of the largest dataset in colorectal cancer proteomics research. Our strategy reveals a disease driven omics-pattern for the metastasis colorectal cancer.

SUBMITTER: Yin X

PROVIDER: S-EPMC4648419 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Large scale systematic proteomic quantification from non-metastatic to metastatic colorectal cancer.

Yin Xuefei X Zhang Yang Y Guo Shaowen S Jin Hong H Wang Wenhai W Yang Pengyuan P

Scientific reports 20150715

A systematic proteomic quantification of formalin-fixed, paraffin-embedded (FFPE) colorectal cancer tissues from stage I to stage IIIC was performed in large scale. 1017 proteins were identified with 338 proteins in quantitative changes by label free method, while 341 proteins were quantified with significant expression changes among 6294 proteins by iTRAQ method. We found that proteins related to migration expression increased and those for binding and adherent decreased during the colorectal c ...[more]

PMID: 26175278

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Project description:BACKGROUND: Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements. Moreover, there is increasing evidence that S100 proteins are often up-regulated in many cancers, including breast, and this is frequently associated with tumour progression. METHODS: Samples of breast cancer tissues were obtained during surgical intervention, according to the bioethical recommendations, and cryo-preserved until used. Tissue extracts were submitted to proteomic preparations for 2D-IPG. Protein identification was performed by N-terminal sequencing and/or peptide mass finger printing. RESULTS: The majority of the detected S100 proteins were absent, or present at very low levels, in the non-tumoral tissues adjacent to the primary tumor. This finding strengthens the role of S100 proteins as putative biomarkers. The proteomic screening of 100 cryo-preserved breast cancer tissues showed that some proteins were ubiquitously expressed in almost all patients while others appeared more sporadic. Most, if not all, of the detected S100 members appeared reciprocally correlated. Finally, from the perspective of biomarkers establishment, a promising finding was the observation that patients which developed distant metastases after a three year follow-up showed a general tendency of higher S100 protein expression, compared to the disease-free group. CONCLUSIONS: This article reports for the first time the comparative proteomic screening of several S100 protein members among a large group of breast cancer patients. The results obtained strongly support the hypothesis that a significant deregulation of multiple S100 protein members is associated with breast cancer progression, and suggest that these proteins might act as potential prognostic factors for patient stratification. We propose that this may offer a significant contribution to the knowledge and clinical applications of the S100 protein family to breast cancer.

Project description:Background and aimsAccumulated evidence indicates that the intestinal microbiota plays crucial roles in the initiation and progression of colorectal cancer (CRC). However, the effects of the tissue-associated microbiota on CRC metastasis are poorly defined. The aim of this study was to explore the differences in bacteria between metastatic and non-metastatic CRC tissues and identify potential bacterial species that associate with CRC metastasis.Methods16S rDNA amplicon high-throughput sequencing was used to test the intestinal tissue-associated microbiota in patients with metastatic CRC (n = 48) and non-metastatic CRC (n = 44). The microbial diversity and differential species were analysed by standard microbiological methods, and then the differential bacteria were confirmed by qPCR. Receiver operating characteristic (ROC) curves were plotted to evaluate the ability of the differential bacteria in predicting the metastasis of CRC. In addition, the microbial compositions of tumor-adjacent tissues from the metastatic and non-metastatic CRC groups were analysed.ResultsThe α- or β-diversity of microbial community between the metastatic and non-metastatic CRC groups did not exhibit significant differences. However, some bacterial abundances between two groups showed significant differences. At the phylum level, Bacteroidota and Desulfobacterota were significantly higher in the metastatic group than in the non-metastatic group, while Proteobacteria was significantly decreased in the metastatic group. At the genus level, Bacteroides (mainly composed of Bacteroides fragilis and Bacteroides uniformis) was significantly higher in the metastatic group than in the non-metastatic group, while Streptococcus and Escherichia-Shigella were significantly decreased. The ROC curves of the selected bacteria showed area under the curve (AUC) values ranging from 0.598 to 0.69; when CEA and the selected bacteria were combined, the AUC values increased from 0.678 to 0.705. In addition, the bacterial composition of tumor-adjacent tissues from the metastatic and non-metastatic CRC groups were also different, and the differential bacteria were consistent with those between metastatic and non-metastatic CRC tumor tissues.ConclusionThe bacterial composition of tumor and tumor adjacent tissue from the metastatic CRC group was different from that of the non-metastatic CRC group; in particular, Bacteroides was increased, and Streptococcus was decreased. These findings are helpful to further reveal the mechanism of CRC metastasis and provide new ideas for the clinical diagnosis and treatment of CRC metastasis.

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Large scale systematic proteomic quantification from non-metastatic to metastatic colorectal cancer.

Publications

Large scale systematic proteomic quantification from non-metastatic to metastatic colorectal cancer.

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