Expression profiling identifies chemokine (C-C motif) ligand 18 as an independent prognostic indicator in gastric cancer

Leung, Suet Yi; Yuen, Siu Tsan; Chu, Kent‐Man; Mathy, Jonathan A.; Li, Rui; Chan, Acy; Law, Simon; Wong, John; Chen, Xin; So, Samuel

doi:10.1053/j.gastro.2004.05.031

Cited by 90 publications

(94 citation statements)

References 34 publications

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“…In the study from Leung et al 16 and in our investigations in MF, CCL18 was preferentially expressed by macrophages. These were defined by expression of CD163 and co-expressed CD209.…”

Section: Discussionsupporting

confidence: 62%

“…26,27 In addition to CTCL, CCL18 up-regulation has been described in B-cell leukemia 15 and in gastric and ovarian cancer. 16,28 The expression of CCL18 by CD68 ϩ macrophages in the tumor invasion front was first described in gastric cancer. 16 In a group of 59 patients, those expressing high serum levels of CCL18 had a better prognosis, leading the authors to conclude that CCL18 levels were a prognostic factor for predicting overall and disease-free survival.…”

Section: Discussionmentioning

confidence: 99%

“…16,28 The expression of CCL18 by CD68 ϩ macrophages in the tumor invasion front was first described in gastric cancer. 16 In a group of 59 patients, those expressing high serum levels of CCL18 had a better prognosis, leading the authors to conclude that CCL18 levels were a prognostic factor for predicting overall and disease-free survival. 16 Unfortunately, the small number of patients in our study did not allow a statistical evaluation of CCL18 expression levels and prognosis in MF tumor patients.…”

Section: Discussionmentioning

confidence: 99%

“…14 Regarding its implication in tumor pathogenesis, elevated serum concentrations of CCL18 have been detected in childhood acute lymphoblastic leukemia, 15 and CCL18 expression was increased in patients with gastric cancer, where it was associated with prolonged overall survival. 16 CCL18 expression can be induced by IL-4. 11 Because the T H 2 cytokine IL-4 was shown to be expressed in lesional skin of patients with both parapsoriasis en plaque (PEP) and MF, 17 CTCL lesions represent a suitable environment for up-regulation of CCL18.…”

mentioning

confidence: 98%

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Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Günther

Zimmermann

Berndt

et al. 2011

The American Journal of Pathology

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Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma (CTCL), which can deteriorate from patch stage to dermal-based tumors and systemic involvement in years. The interaction of chemokines in the skin with CTCL cells might have implications for the pathogenesis of the disease. In this study, we show by PCR analysis and immunofluorescence staining that the chemokine CCL18 is present in skin biopsy specimens of patients with MF and its precursor form parapsoriasis en plaque but not in healthy tissue. In addition, the serum levels of CCL18 were increased threefold in MF patients compared with those in healthy controls. In skin, CCL18 was specifically expressed by CD163 ؉ CD209 ؉ macrophages at the invasive margin of the tumor and not expressed by mature CD208 ؉ dendritic cells in the center of the tumor. The chemokine CCL17 was, by contrast, ubiquitously expressed. Furthermore, CCL18 promoted the chemotaxis but not the proliferation of CTCL cells. CCL18 inhibited proliferation of tumor cells and abolished the CXCL12-induced growth of a CTCL cell line. These data link the increased expression of CCL18 with CTCL and suggest an immunomodulatory effect of the chemokine in the pathogenesis

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“…In the study from Leung et al 16 and in our investigations in MF, CCL18 was preferentially expressed by macrophages. These were defined by expression of CD163 and co-expressed CD209.…”

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

See 2 more Smart Citations

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Günther

Zimmermann

Berndt

et al. 2011

The American Journal of Pathology

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“…Some authors also demonstrate that the level of CCL18 is elevated in body fluids and serum of patients with ovarian carcinoma [14,15]. Examination of tumor tissue located the origin of CCL18 in a subpopulation of TAMs based at the tumor front [16]. Interestingly CCL18 shows some similarity to TGF-ß, but the role of CCL18 in the tumor environment of NSCLC is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Serum Level of CC-Chemokine Ligand 18 is Increased in Patients with Non-small-cell Lung Cancer and Correlates with Survival Time in Adenocarcinomas

et al. 2012

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CC-chemokine ligand18 (CCL18) ismainly expressed by alternativelyactivated macrophages and DCs and plays an important role in lung fibrosis, arthritis and other diseases. Here CCL18 was measured in sera of 31 healthy volunteers and 170 patients with lung cancer and correlatedthese data with histology, tumor stage and clinicalparameters. Mean CCL18 serum levelofthe patients with non-small-cell lung cancer was 150(857) ng/ml vs. 32(61) ng/ml in the healthy control group. Patient groups differ significantly according their histology (adenocarcinoma 143(528) ng/ml vssquamous cell carcinoma 187(857) ng/ml, p,0.02). In addition, we found a significant difference between patients with lower versus higher T-stage (p,0.003). Receiver operating characteristic (ROC) analyses revealed a cutoff point of 83 ng/ml (area under the curve (AUC): 0.968; p,0.0001) to discriminate between healthy controls and non-small-cell lung cancer patients. ROC analyses to discriminate between patients, who died because of cancer related death and those who died for other reasons did not lead to a valid AUC. To stratify the tumor patients, a criterion value plot was performed leading to a point of equal sensitivity and specificity (54%) of 162 ng/ml. Patients with a CCL18 serum level higher than 160 ng/ml had a mean survival time of 623 days. In contrast, those in patients with a baseline level between 83 ng/ml and 160 ng/ml the mean survival time was 984 days (p,0.005). Survival-analysis revealed in adenocarcinoma a mean survival of 1152 days in the group below 83 ng/ml. In the median group the mean survival time was 788 days and in the group with the highest levels the mean survival time was 388 days (p,0.001). In contrast, we found no correlation between the FEV1 and the CCL18 baseline level. In conclusion, in patients suffering from adenocarcinoma increased serum CCL18 levels predict a diminished survival time.

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GeneExpressScore Signature: a robust prognostic and predictive classifier in gastric cancer

et al. 2018

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Although several prognostic signatures have been developed for gastric cancer (GC), the utility of these tools is limited in clinical practice due to lack of validation with large and multiple independent cohorts, or lack of a statistical test to determine the robustness of the predictive models. Here, a prognostic signature was constructed using a least absolute shrinkage and selection operator (LASSO) Cox regression model and a training dataset with 300 GC patients. The signature was verified in three independent datasets with a total of 658 tumors across multiplatforms. A nomogram based on the signature was built to predict disease‐free survival (DFS). Based on the LASSO model, we created a GeneExpressScore signature (GESGC) classifier comprised of eight mRNA. With this classifier patients could be divided into two subgroups with distinctive prognoses [hazard ratio (HR) = 4.00, 95% confidence interval (CI) = 2.41–6.66, P < 0.0001]. The prognostic value was consistently validated in three independent datasets. Interestingly, the high‐GESGC group was associated with invasion, microsatellite stable/epithelial–mesenchymal transition (MSS/EMT), and genomically stable (GS) subtypes. The predictive accuracy of GESGC also outperformed five previously published signatures. Finally, a well‐performed nomogram integrating the GESGC and four clinicopathological factors was generated to predict 3‐ and 5‐year DFS. In summary, we describe an eight‐mRNA‐based signature, GESGC, as a predictive model for disease progression in GC. The robustness of this signature was validated across patient series, populations, and multiplatform datasets.

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Expression profiling identifies chemokine (C-C motif) ligand 18 as an independent prognostic indicator in gastric cancer

Cited by 90 publications

References 34 publications

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Serum Level of CC-Chemokine Ligand 18 is Increased in Patients with Non-small-cell Lung Cancer and Correlates with Survival Time in Adenocarcinomas

GeneExpressScore Signature: a robust prognostic and predictive classifier in gastric cancer

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