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Loss of tumoral expression of soluble IL-6 receptor is associated with disease progression in colorectal cancer.

Okugawa Y, Miki C, Toiyama Y, Yasuda H, Yokoe T, Saigusa S, Hiro J, Tanaka K, Inoue Y, Kusunoki M - Br. J. Cancer (2010)

Bottom Line: Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation.In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

View Article: PubMed Central - PubMed

Affiliation: Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

ABSTRACT

Background: Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients.

Methods: We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis.

Results: Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio <1.0 was significantly associated with factors reflecting disease progression, and was an independent prognostic factor not only in all the patients in this study, but also in the patients with curative intent. Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation. Immunohistochemistry revealed that loss of tumour expression of sIL-6R was significantly inversely correlated with intense IL-6 expression in the cytoplasm of cancer cells. In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.

Conclusion: Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

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Related in: MedlinePlus

(A) Kaplan–Meier data of the actual 5-year survival rates of all patients, according to sIL-6R Ca/N expression ratios. (B) Kaplan–Meier data of the actual 5-year survival rates of UICC stage I, II and III patients undergoing potentially curative surgery except synchronous distant metastasis according to sIL-6R Ca/N expression ratios.
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fig2: (A) Kaplan–Meier data of the actual 5-year survival rates of all patients, according to sIL-6R Ca/N expression ratios. (B) Kaplan–Meier data of the actual 5-year survival rates of UICC stage I, II and III patients undergoing potentially curative surgery except synchronous distant metastasis according to sIL-6R Ca/N expression ratios.

Mentions: Figure 2A shows the actual survival curves for all colorectal carcinoma patients, subdivided by their sIL-6R Ca/N expression ratio. Patients who lost tumoral sIL-6R expression had significantly poorer prognoses than those with higher tumoral sIL-6R expression (log-rank test, P=0.0003). Figure 2B shows the actual survival curves for UICC stage I, II, and III patients undergoing potentially curative surgery. The curative intent patients who lost tumoral sIL-6R expression also had significantly poorer prognoses than those with higher tumoral sIL-6R expression (log-rank test, P=0.0174). Table 2a reveals the resulting risk ratios and 95% confidence intervals (95% CIs) calculated by Cox proportional hazards analysis in all colorectal cancer patients. In this analysis, hepatic metastasis and loss of tumoral sIL-6R expression were independent risk factors for a poor prognosis. Cox proportional hazards analysis in UICC stage I, II, and III patients similarly showed that loss of tumoral sIL-6R expression was an independent risk factor for a poor prognosis (Table 2b).


Loss of tumoral expression of soluble IL-6 receptor is associated with disease progression in colorectal cancer.

Okugawa Y, Miki C, Toiyama Y, Yasuda H, Yokoe T, Saigusa S, Hiro J, Tanaka K, Inoue Y, Kusunoki M - Br. J. Cancer (2010)

(A) Kaplan–Meier data of the actual 5-year survival rates of all patients, according to sIL-6R Ca/N expression ratios. (B) Kaplan–Meier data of the actual 5-year survival rates of UICC stage I, II and III patients undergoing potentially curative surgery except synchronous distant metastasis according to sIL-6R Ca/N expression ratios.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966622&req=5

fig2: (A) Kaplan–Meier data of the actual 5-year survival rates of all patients, according to sIL-6R Ca/N expression ratios. (B) Kaplan–Meier data of the actual 5-year survival rates of UICC stage I, II and III patients undergoing potentially curative surgery except synchronous distant metastasis according to sIL-6R Ca/N expression ratios.
Mentions: Figure 2A shows the actual survival curves for all colorectal carcinoma patients, subdivided by their sIL-6R Ca/N expression ratio. Patients who lost tumoral sIL-6R expression had significantly poorer prognoses than those with higher tumoral sIL-6R expression (log-rank test, P=0.0003). Figure 2B shows the actual survival curves for UICC stage I, II, and III patients undergoing potentially curative surgery. The curative intent patients who lost tumoral sIL-6R expression also had significantly poorer prognoses than those with higher tumoral sIL-6R expression (log-rank test, P=0.0174). Table 2a reveals the resulting risk ratios and 95% confidence intervals (95% CIs) calculated by Cox proportional hazards analysis in all colorectal cancer patients. In this analysis, hepatic metastasis and loss of tumoral sIL-6R expression were independent risk factors for a poor prognosis. Cox proportional hazards analysis in UICC stage I, II, and III patients similarly showed that loss of tumoral sIL-6R expression was an independent risk factor for a poor prognosis (Table 2b).

Bottom Line: Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation.In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

View Article: PubMed Central - PubMed

Affiliation: Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

ABSTRACT

Background: Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients.

Methods: We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis.

Results: Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio <1.0 was significantly associated with factors reflecting disease progression, and was an independent prognostic factor not only in all the patients in this study, but also in the patients with curative intent. Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation. Immunohistochemistry revealed that loss of tumour expression of sIL-6R was significantly inversely correlated with intense IL-6 expression in the cytoplasm of cancer cells. In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.

Conclusion: Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

Show MeSH
Related in: MedlinePlus