Cyclooxygenase-2 Expression Is an Independent Predictor of Poor Prognosis in Colon Cancer

Ogino, Shuji; Kirkner, Gregory J.; Nosho, Katsuhiko; Irahara, Natsumi; Kure, Shoko; Shima, Kaori; Hazra, Aditi; Chan, Andrew T.; Dehari, Reiko; Giovannucci, Edward; Fuchs, Charles S.

doi:10.1158/1078-0432.ccr-08-1841

Cited by 186 publications

(149 citation statements)

References 47 publications

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“…Hence, we were able to confirm results from previous, smaller scale studies in UM 22,23 and other malignancies. [30][31][32] In summary, a higher immunoreactivity score for COX-2 staining was associated with a worse OS. In contrast to previous studies on UM, we observed no correlation between high COX-2 expression and the prevalence of the epitheloid cell type.…”

Section: Discussionmentioning

confidence: 82%

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Mougiakakos

Johansson

Trocmé

et al. 2010

Cancer

112

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BACKGROUND: Forkhead box P3 (FOXP3)-positive regulatory T cells (Tregs) are key mediators of peripheral tolerance and suppress efficient antitumor responses. Prostaglandin E 2 (PGE 2 ) produced by inducible cyclooxygenase-2 (COX-2) can lead to Treg induction. COX-2 expression has been linked to tumorigenesis and growth in various malignancies. The objective of the current study was to investigate whether Tregs infiltrate uveal melanomas (UMs) and whether their prevalence is linked to COX-2 expression and the prediction of overall survival (OS). METHODS: One hundred patients who underwent enucleation after they were diagnosed with UM were included in the study. Immunohistochemical staining with monoclonal anti-FOXP3, anti-CD4, and anti-COX-2 antibodies was performed, and immunoreactivity was assessed. Correlations of COX-2 expression with the presence of Tregs, established clinicopathologic parameters, and OS were evaluated in univariate and multivariate analyses. RESULTS: High expression of COX-2 was predictive of shortened OS. FOXP3-positive Tregs were detectable in 24% of UMs and were restricted to malignant tissue. The extent of COX-2 expression was associated significantly with Treg prevalence (P ¼ .004) and Treg intratumoral localization (P ¼ .005). Intratumoral Tregs (but not the prevalence of Tregs) were independent marker for worse OS with a hazard ratio of 5.36 in patients with COX-2-positive tumors. CONCLUSIONS:The current results demonstrated that high COX-2 expression is associated with OS and Treg prevalence in UM. These findings are in line with the observations that COX-2/PGE 2 induces Tregs and that Tregs may alter antitumor responses, resulting in a negative effect on the clinical disease course. Intratumoral Tregs are an independent prognostic marker for COX

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Section: Discussionmentioning

confidence: 82%

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Mougiakakos

Johansson

Trocmé

et al. 2010

Cancer

112

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“…Cyclooxygenase-2 is also considered to have an important role in colorectal carcinogenesis. Recently, Ogino et al (2008) reported that Cox-2 overexpression is associated with worse survival among colon cancer patients. Nuclear factor-kB is an end point of the TLR4/ MyD88 signalling pathway.…”

Section: Discussionmentioning

confidence: 99%

High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer

et al. 2010

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BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P ¼ 0.0001, P ¼ 0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15 -4.07; P ¼ 0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31 -4.13; P ¼ 0.0038 and HR: 3.03; 95% CI: 1.67 -5.48; P ¼ 0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27 -3.99; P ¼ 0.0053 and HR: 2.97; 95% CI: 1.64 -5.38; P ¼ 0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99 -3.55; P ¼ 0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01 -3.67; P ¼ 0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17 -4.33; P ¼ 0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.

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“…COX-2 is related to the formation of carcinogens, tumor promotion, apoptosis inhibition, angiogenesis development, and metastatic process (Meric et al, 2006). Up-regulation of expression of COX-2 has been associated with human intestinal inflammation, colorectal cancer (Wang and Dubois, 2010) and worse survival among CRC patients (Ogino et al, 2008). Therefore, COX-2 expression may be used to monitor the process of carcinogenesis, and the suppression of COX-2 expression can become a target for cancer chemoprevention (Singh et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Suppression of β-catenin and Cyclooxygenase-2 Expression and Cell Proliferation in Azoxymethane-Induced Colonic Cancer in Rats by Rice Bran Phytic Acid (PA)

Esa¹,

Ithnin²

2013

Asian Pacific Journal of Cancer Prevention

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Background: Phytic acid (PA) is a polyphosphorylated carbohydrate that can be found in high amounts in most cereals, legumes, nut oil, seeds and soy beans. It has been suggested to play a significant role in inhibition of colorectal cancer. This study was conducted to investigate expression changes of β-catenin and cyclooxygenase-2 (COX-2) and cell proliferation in the adenoma-carcinoma sequence after treatment with rice bran PA by immunocytochemistry. Materials and Methods: Seventy-two male Sprague-Dawley rats were divided into 6 equal groups with 12 rats in each group.

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Cyclooxygenase-2 Expression Is an Independent Predictor of Poor Prognosis in Colon Cancer

Cited by 186 publications

References 47 publications

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer

Suppression of β-catenin and Cyclooxygenase-2 Expression and Cell Proliferation in Azoxymethane-Induced Colonic Cancer in Rats by Rice Bran Phytic Acid (PA)

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