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CCR6 is a prognostic marker for overall survival in patients with colorectal cancer, and its overexpression enhances metastasis in vivo.

ABSTRACT: The chemokine receptor CCR6 has been recently shown to be associated with colorectal cancer (CRC) progression. However, the direct evidence for whether CCR6 in tumors is a prognostic marker for the survival of patients with CRC and whether it plays a critical role in CRC metastasis in vivo is lacking. Here we show that the levels of CCR6 were upregulated in CRC cell lines and primary CRC clinical samples. CCR6 upregulation was closely correlated with disease stages and the survival time of CRC patients. Knockdown of CCR6 inhibited the migration of CRC cells in vitro. Overexpression of CCR6 in CRC cells increased their proliferation, migration, and colony formation in vitro and promoted their metastatic potential in vivo. CCR6 activated Akt signaling, upregulated metastasis genes and downregulated metastasis suppressor genes. Selective targeting of CCR6 in tumors dramatically inhibited the growth of CRC in mice. Thus, the tumor expression of CCR6 plays a critical role in CRC metastasis, upregulated CCR6 predicts poor survival in CRC patients, and targeting CCR6 expression in tumors may be a potential therapeutic strategy for CRC.

SUBMITTER: Liu J

PROVIDER: S-EPMC4076197 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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CCR6 is a prognostic marker for overall survival in patients with colorectal cancer, and its overexpression enhances metastasis in vivo.

Liu Jinlin J Ke Fang F Xu Zhenyao Z Liu Zhaoyuan Z Zhang Lingyun L Yan Sha S Wang Zhe Z Wang Hong H Wang Honglin H

PloS one 20140630 6

The chemokine receptor CCR6 has been recently shown to be associated with colorectal cancer (CRC) progression. However, the direct evidence for whether CCR6 in tumors is a prognostic marker for the survival of patients with CRC and whether it plays a critical role in CRC metastasis in vivo is lacking. Here we show that the levels of CCR6 were upregulated in CRC cell lines and primary CRC clinical samples. CCR6 upregulation was closely correlated with disease stages and the survival time of CRC p ...[more]

PMID: 24979261

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Project description:BackgroundLipid disequilibrium and systemic inflammation are reported to correlate with tumorigenesis and development of colorectal cancer (CRC). We construct the novel biomarker cholesterol-to-lymphocyte ratio (CLR) to reflect the synergistic effect of cholesterol metabolism and inflammation on CRC outcomes. This study aims to investigate the clinical significance of CLR and establish a prognostic model for CRC.MethodsOur study retrospectively enrolled 223 CRC patients who underwent curative surgical resection. The Kaplan-Meier method was employed to estimate the overall survival (OS) rates, and the association between serological biomarkers and survival was assessed with a log-rank test. Cox proportional hazard regression was applied in the univariate and multivariate analyses to identify independent prognostic factors, which were then used to develop a predictive nomogram model for OS in CRC. The nomogram was evaluated by the C-index, receiver operator characteristic curve (ROC) analysis, and calibration plot. All cases were grouped into three stratifications according to the total risk points calculated from the nomogram, and the difference in OS between them was assessed with the Kaplan-Meier method.ResultsAt the end of the study, death occurred in 47 (21%) cases. Patients with low CLR (< 3.23) had significantly prolonged survival (P < 0.001). Multivariate analyses revealed that N stage (P < 0.001), harvested lymph nodes (P = 0.021), and CLR (P = 0.005) were independent prognostic factors for OS and a prognostic nomogram was established based on these variables. The nomogram showed good calibration and predictive performance with a superior C-index than TNM stage (0.755 (0.719-0.791) vs. 0.663 (0.629-0.697), P = 0.001). Patients of different risk stratifications based on the total score of nomogram showed distinct survival (P < 0.001).ConclusionsThe nomogram based on CLR and other clinical features can be used as a potentially convenient and reliable tool in predicting survival in patients with CRC.

Dataset Information

CCR6 is a prognostic marker for overall survival in patients with colorectal cancer, and its overexpression enhances metastasis in vivo.

Publications

CCR6 is a prognostic marker for overall survival in patients with colorectal cancer, and its overexpression enhances metastasis in vivo.

Similar Datasets

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