scholarly journals Expression profiles of 507 proteins from a biotin label-based antibody array in human colorectal cancer

2013 ◽  
Vol 31 (3) ◽  
pp. 1277-1281 ◽  
Author(s):  
HISAAKI MIYOSHI ◽  
ASAHIRO MORISHITA ◽  
JOJI TANI ◽  
TEPPEI SAKAMOTO ◽  
KOJI FUJITA ◽  
...  
2020 ◽  
Author(s):  
Hong Wang ◽  
David H Wang ◽  
Xu Yang ◽  
Yuhai Sun ◽  
Chung S Yang

Abstract Colitis increases the risk of colorectal cancer; however, the mechanism of the association between colitis and cancer remains largely unknown. To identify colitis-associated cancer promoting factors, we investigated gene expression changes caused by dextran sulfate sodium (DSS)-induced colitis in mice. By analyzing gene expression profiles, we found that IL11 was upregulated in DSS-induced colitis tissue and 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP)/DSS-induced colon tumors in mice as well as in human colorectal cancer. By characterizing the activation/phosphorylation of STAT3 (pSTAT3), we found that pSTAT3 was induced transiently in colitis, but maintained at higher levels from hyper-proliferative dysplastic lesions to tumors. Using the IL11 receptor (IL11Rα1) knockout mice, we found that pSTAT3 in the newly regenerated crypt epithelial cells in colitis is abolished in IL11Rα1+/- and -/- mice, suggesting that colitis-induced IL11 activates STAT3 in colon crypt epithelial cells. Moreover, colitis-promoted colon carcinogenesis was significantly reduced in IL11Rα1+/- and -/- mice. To determine the roles of the IL11 in colitis, we found that the inhibition of IL11 signaling by recombinant IL11 antagonist mutein during colitis was sufficient to attenuate colitis-promoted carcinogenesis. Together, our results demonstrated that colitis-induced IL11 plays critical roles in creating cancer promoting microenvironment to facilitate the development of colon cancer from dormant premalignant cells.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3611-3611
Author(s):  
M. Han ◽  
C. T. Liew ◽  
H. W. Zhang ◽  
K. T. Yip ◽  
Z. Y. Song ◽  
...  

3611 Background: Human colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, and early detection is critical to improve prognosis. To date, we have applied our unique methodology (the Sentinel Principle) to identify blood-based gene expressed biomarkers for several diseases including osteoarthritis, bladder cancer and psychiatric disorders. In the present CRC study, we identified gene signatures from blood cells and characterized a set of biomarkers able to differentiate patients with CRC from controls. Methods: Microarray: 31 blood RNA sample (15 controls; 16 CRC) were profiled using Affymetrix U133Plus2.0 GeneChips. Differentially expressed genes were identified using the non-parametric, Wilcoxon-Mann-Whitney test. SYBR Green real-time RT-PCR: a subset of identified genes was assayed using 115 samples (57 controls; 58 CRC). Logistic regression was used to assess the ability of linear combinations of specific transcripts to distinguish CRC from controls. The diagnostic power for each combination was evaluated by AUC of the Receiver Operating Characteristic (ROC) curve. Blind Test: 83 samples were assayed (45 controls and 38 CRC). Results: Microarray data: 2,779 probes were significantly different in blood gene expression profiles from controls and those from CRC (p<0.05). Real-time RT-PCR: Two up-regulated genes (cytidine deaminase, 1.3 fold with p<0.001; MGC20553 /FERM domain containing 3, 1.2 fold with p=0.031) and three down-regulated genes were validated (B-cell scaffold protein with ankyrin repeats 1, 0.43 fold with p<0.001; B-cell novel protein 1, 0.44 fold with p<0.001; membrane-spanning 4-domains, subfamily A, member 1, 0.44 with p<0.001). Combination analysis: The AUC was 0.883 (95%, C.I. 0.810–0.935) for the best linear combination of these 5 genes. At a cut-off of -1.1, the sensitivity and specificity were 98% and 51%, respectively. Blind Test: The 5-gene set gave sensitivity of 95% (36/38) and specificity of 42% (19/45) with an overall accuracy of 66%. Conclusions: Gene expression signatures from peripheral blood differentiate between CRC patients and controls. The five-gene panel showed high classification performance and could be used as a novel screening tool for CRC. [Table: see text]


Sign in / Sign up

Export Citation Format

Share Document