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

Abstract

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.

CC chemokine ligand 18(CCL18) promotes migration and invasion of lung cancer cells by binding to Nir1 through Nir1‐ELMO1/DOC180 signaling pathway

“…We have previously demonstrated that CCL18 binds to Nir1 and plays a critical role in inducing epithelial‐mesenchymal transition (EMT) of breast cancer . Recently, it is reported that serum level of CCL18 is increased in NSCLC and correlates with survival time in adenocarcinomas . By coincidence, our pilot study showed that CCL18 can promote the migration and invasion of lung cancer cells.…”

Local Concentrations of CC-Chemokine-Ligand 18 Correlate with Tumor Size in Non-small Cell Lung Cancer and Are Elevated in Lymph Node-positive Disease

“…Previous studies on lung cancer demonstrated that the accumulation of CCL18-positive TAMs in pathological sections was associated with a poor prognostic outcome (22). Correspondingly, high serum concentrations of CCL18 in lung adenocarcinoma were also associated with an unfavorable prognosis (23).…”

Dissecting gene‐environment interactions: A penalized robust approach accounting for hierarchical structures

“…Overexpression of AQP1 has been found to be associated with a poor survival in lung adenocarcinoma (Yun et al). Lung cancer patients with a higher serum CCL18 level have a shorter survival (Pl nes et al).…”