Elevated Serum Levels of CCL23 Are Associated with Poor Outcome after Resection of Biliary Tract Cancer

Abstract

Background. Surgical tumor resection is the only potentially curative treatment option for patients with biliary tract cancer (BTC). However, 5-year survival rates are still below 50% mainly due to tumor recurrence. The preoperative identification of ideal surgical candidates has remained a major challenge and easily accessible algorithms including parameters of the individual tumor biology are missing. Chemokine (C-C motif) ligand 23 (CCl23) has been associated with tumor progression in hepatocellular carcinoma (HCC), but its role in the context of BTC is largely unknown. Here, we evaluated circulating levels of CCL23 as potential diagnostic and prognostic biomarker in patients with resectable BTC. Methods. CCl23 serum levels were analyzed by multiplex immunoassay in a cohort of 119 BTC patients receiving surgical tumor resection as well as 50 healthy control samples and 11 patients with primary sclerosing cholangitis (PSC). Results. Baseline serum CCL23 levels were significantly elevated in BTC patients compared to PSC patients as well as healthy controls. CCL23 increased the diagnostic sensitivity and specificity of established tumor markers including CA19-9 and correlated with patients’ age and makers of systemic inflammation. Elevated preoperative CCL23 levels were associated with a significantly impaired postoperative outcome. BTC patients with a preoperative CCL23 level above the optimal prognostic cut-off value of 702.4 pg/ml showed a median OS of only 110 days compared to 501 days for patients with low initial CCL23 levels. The prognostic value of circulating CCL23 was confirmed in Cox-regression analysis. Conclusion. Serum levels of CCL23 are elevated in patients with BTC, and high preoperative CCL23 levels were associated with an impaired postoperative survival. CCL23 serum levels could help to identify the ideal surgical candidates for BTC resection in the future.

Racial differences in serum chemokines in prostate cancer patients

“…For CXCL2, a median value of 301.44 (217.6–422.3) pg/mL is reported in healthy controls, whereas serum CXCL5 values ranged from 98.7 and up to ∼3000 pg/mL 41–43 . Similarly, a recent study reported a CCL23 median value of 266.6 (32.1–652.5) pg/mL in healthy controls 44 . However, in these studies, the healthy controls include both males and females.…”

“…[41][42][43] Similarly, a recent study reported a CCL23 median value of 266.6 (32.1-652.5) pg/mL in healthy controls. 44 However, in these studies, the healthy controls include both males and females. It is worth pointing out that these values can vary widely among different laboratories with different testing methods.…”

Serum protein profiling reveals an inflammation signature as a predictor of early breast cancer survival

“…Nevertheless, high breast cancer tissue CCL8 mRNA tissue levels have been reported to increase in breast cancers compared to adjacent healthy tissues and to be associated with worse RFS [32,34]. In biliary tract cancers, elevated serum CCL23 predicted a dismal prognosis [35], and PEA-measured high plasma CCL28 levels implied worse survival in epithelial ovarian cancers [36]. Again, CCL28 levels in tumor tissue have a favorable prognostic role in luminal breast cancer but are associated with a worse prognosis in TNBC [37].…”

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

“…CCL23, also known as macrophage inflammatory protein 3 (MIP-3), is secreted by different immune cell types, including eosinophils, neutrophils, and monocytes [ 180 ]. Through the interaction with its ligand CCR1, this chemokine has a chemotactic effect on monocytes/macrophages, dendritic cells, lymphocytes, and ECs, and it is also able to promote angiogenesis [ 180 ]. Serum levels of CCL23 were found to be higher in SSc patients with respect to healthy individuals, and to associate with disease activity and shorter disease duration [ 181 ].…”