Dataset Information

Glycan analysis of colorectal cancer samples reveals stage-dependent changes in CEA glycosylation patterns.

ABSTRACT: Background:Carcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal cancer (CRC). While the functions of its gene and protein have been fully characterized, its post-translational modifications in the context of CRC development remain undefined. Methods:To show the correlation between the different stages of CRC development and changes in the glycosylation patterns of CEA, we analyzed CEA in tumor tissues (CEA-T) and paired tumor-adjacent normal tissues (CEA-A) from 53 colorectal cancer patients using a high-density lectin microarray containing 56 plant lectins. Results:We detected higher expression levels of fucose, mannose and Thomsen-Friedenreich antigen, and lower expression levels of N-acetylgalactosamine, N-acetylglucosamine, galactose, branched and bisecting N-glycans on CEA in the tumor tissues relative to the tumor-adjacent normal tissues. Furthermore, a combinatorial assessment of 9 lectins is sufficient to distinguish CRC tumor tissues from tumor-adjacent normal tissues with 83% sensitivity and ~ 90% specificity. Moreover, the levels of N-acetylgalactosamine, mannose, galactose, N-acetylglucosamine on CEA showed a downward trend after first experiencing an increase at Stage II with the stages of CRC. Conclusions:Our insights into the changing CEA glycosylation patterns and their role in the development of CRC highlight the importance of glycan variants on CEA for early clinical detection and staging of CRC.

SUBMITTER: Zhao Q

PROVIDER: S-EPMC5834848 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Glycan analysis of colorectal cancer samples reveals stage-dependent changes in CEA glycosylation patterns.

Zhao Qianqian Q Zhan Tiancheng T Deng Zaian Z Li Qianqian Q Liu Yaming Y Yang Shaojie S Ji Dengbo D Li Yan Y

Clinical proteomics 20180302

<h4>Background</h4>Carcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal cancer (CRC). While the functions of its gene and protein have been fully characterized, its post-translational modifications in the context of CRC development remain undefined.<h4>Methods</h4>To show the correlation between the different stages of CRC development and changes in the glycosylation patterns of CEA, we analyzed CEA in tumor tissues (CEA-T) and paired tumor-adjacent normal tissues (CEA-A) ...[more]

PMID: 29507546

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Project description:Background: Carcinoembryonic antigen (CEA) is the most common serum tumor marker in colorectal cancer (CRC). Nevertheless, few previous studies demonstrated the impacts of postoperative CEA and post-preoperative CEA increment on prognosis of CRC. Methods: Patients with stage II and III CRC were included from January 2009 to December 2015. All clinical and follow-up data were collected. Patients were divided into four different groups according to the levels of postoperative serum CEA and post-preoperative CEA trends. Chi-square test was used to analyze the relationship between clinical variables and categorized postoperative CEA and CEA increment. Cox proportional hazard regression was used for univariate and multivariable analyses. The log-rank test was performed to compare PFS and OS among groups. Results: Patients, 1,008, who underwent radical surgery, were enrolled. Our results showed that positive postoperative CEA and CEA increment were related to clinical stage, T stage, N stage, tumor differentiation, and lymphatic invasion (p < 0.05). Univariate and multivariable analysis results suggested that positive postoperative CEA and CEA increment were independent prognostic factors for PFS (HR = 3.149, 95% CI, 2.426-4.088, p = 0.000 for postoperative CEA; HR = 2.708, 95% CI, 2.106-3.482, p = 0.000 for CEA increment) and OS (HR = 3.414, 95% CI, 2.549-4.574, p = 0.000 for postoperative CEA; HR = 2.373, 95% CI, 1.783-3.157, p = 0.000 for CEA increment). The survival analyses revealed positive postoperative CEA, and CEA increment predicted worse prognosis. Furthermore, our results indicated that the 3- and 5-year PFS rates were 86.6 and 78.4% in group A, but decreased to 25.3 and 7.2% in group D (p < 0.001). Similarly, the 3- and 5-year OS rates for group A were 92.5 and 83.9%, much higher than group D (p < 0.001). In other words, patients with both postoperative CEA elevation and CEA increment had the worst prognosis. Conclusions: Positive postoperative CEA and CEA increment were independent prognostic factors for stage II and III CRC. Additionally, postoperative CEA and CEA increment had significant impacts on PFS and OS of CRC.

Project description:Brugia malayi is a nematode parasite that causes lymphatic filariasis, a disfiguring and disabiling tropical disease. Although a first draft genome sequence was released in 2007, very little is understood about transcription programs that govern developmental changes required for the parasite's development and survival in its mammalian and insect hosts.We used a microarray with probes that represent some 85% of predicted genes to generate gene expression profiles for seven parasite life cycle stages/sexes. Approximately 41% of transcripts with detectable expression signals were differentially expressed across lifecycle stages. Twenty-six percent of transcripts were exclusively expressed in a single parasite stage, and 27% were expressed in all stages studied. K-means clustering of differentially expressed transcripts revealed five major transcription patterns that were associated with parasite lifecycle stages or gender. Examination of known stage-associated transcripts validated these data sets and suggested that newly identified stage or gender-associated transcripts may exercise biological functions in development and reproduction. The results also indicate that genes with similar transcription patterns were often involved in similar functions or cellular processes. For example, nuclear receptor family gene transcripts were upregulated in gene expression pattern four (female-enriched) while protein kinase gene family transcripts were upregulated in expression pattern five (male-enriched). We also used pair-wise comparisons to identify transcriptional changes between life cycle stages and sexes.Analysis of gene expression patterns of lifecycle in B. malayi has provided novel insights into the biology of filarial parasites. Proteins encoded by stage-associated and/or stage-specific transcripts are likely to be critically important for key parasite functions such as establishment and maintenance of infection, development, reproduction, and survival in the host. Some of these may be useful targets for vaccines or new drug treatments for filariasis.

Dataset Information

Glycan analysis of colorectal cancer samples reveals stage-dependent changes in CEA glycosylation patterns.

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Glycan analysis of colorectal cancer samples reveals stage-dependent changes in CEA glycosylation patterns.

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