The Correlation Between Serum Chemokines and Clinical Outcome in Patients with Advanced Biliary Tract Cancer

Abstract

BACKGROUND: Biliary tract cancers (BTCs) are known to have a dismal prognosis. A number of chemokines play important roles in the progress of BTCs. However, the serum levels of chemokines in BTCs have not yet been explored. METHODS: The sera of healthy donors (n = 8) and patients with BTCs who were enrolled in second line sunitinib trials (n = 27) were collected. The concentrations of three kinds of chemokines (CXCL5, CXCL8 and CXCL12) were measured using ELISA assay. The median concentrations of chemokines were compared between healthy donors and BTC patients and the role of chemokines as a prognostic biomarker was examined. RESULTS: BTC patients generally had higher serum levels of CXCL5 and CXCL12 compared to healthy donors. Patients with cholangiocarcinoma showed significantly higher levels of serum CXCL12 than patients with gallbladder cancer. In survival analysis, only CXCL12 level showed a prognostic impact on overall survival (median OS: 6.9 vs. 0.9 months in low CXCL12 vs. high CXCL12, respectively; P = .008). High CXCL5 levels were also correlated with poor survival without statistical insignificance (median OS: 6.2 vs. 2.0 months in low CXCL5 vs. high CXCL5, respectively; P = .070). CONCLUSIONS: There was a significant difference in OS according to the level of CXCL12, suggesting that serum CXCL12 levels may be a useful surrogate marker for clinical outcome in advanced BTCs.

Prognostic significance of CXCL5 expression in cancer patients: a meta-analysis

“…The follow-up time ranged from 23 months to 180 months. Ten different types of cancer were involved in the enrolled studies including intrahepatic cholangiocarcinoma (n = 2) [ 27 , 31 ], lung cancer (n = 3) [ 26 , 32 , 33 ], colorectal cancer (n = 3) [ 34 – 36 ], biliary tract cancer (n = 1) [ 10 ], breast cancer (n = 1) [ 5 ], bladder cancer (n = 1) [ 19 ], glioma (n = 1) [ 18 ], pancreatic cancer (n = 1) [ 25 ], hepatocellular carcinoma (n = 1) [ 24 ] and nasopharyngeal carcinoma (n = 1) [ 37 ]. Among these studies, OS (n = 14), DFS (n = 3), PFS (n = 3) and RFS (n = 3) were estimated as survival outcome.…”

“…Chemokines and their receptors could bring about the transcription of target genes involved in cell invasion, motility, survival and interactions with the extracellular matrix, which can induce migration, chemotaxis and rearrangement of the cytoskeleton in the target cell, and therefore promote multiple physiological functions of cells, including cell growth, development, differentiation and apoptosis [ 6 – 9 ]. Over the past few years, accumulating evidence has revealed that chemokines play pivotal roles in progression of tumor [ 10 ]. Chemokines produced by tumor and stromal cells can induce the expression and distribution of tumor-associated leukocytes, trigger angiogenesis, contribute to the growth and metastasis of malignant cells and generate fiber keratinocytes [ 6 , 11 , 12 ].…”

CXCL5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target

“…According to the previous studies, more than 14 different malignant tumor types, including breast cancer [15], bladder cancer [16], non-small cell lung cancer [17], gastric cancer [18], head and neck squamous cell carcinoma [19], cholangiocarcinoma [20], hepatocellular carcinoma [21], prostate cancer [22], pancreatic cancer [23], colorectal cancer [24], glioma [25], endometrial cancer [26], nasopharyngeal carcinoma [27], and squamous carcinoma of larynx [6], had high expression of CXCL5 when compared to para-carcinoma or normal tissues (Table 1). By identifying and validating the genes regarding the development of gastric cancer, researchers have found that CXCL5, as one of the substances, was associated with early stages of the disease [28].…”

Role of Chemokines in the Biology of Cholangiocarcinoma

“…A recent meta-analysis aimed to evaluate the prognostic significance of CXCL5 in CCA patients, revealed that CXCL5 overexpression was inversely correlated with overall survival [ 90 ]. Another recent study, analyzing serum chemokine profiles in CCA, reported that CXCL5 was higher in CCA patients, compared to healthy subjects, and CXCL5 levels correlated with poor prognosis [ 91 ]. These reports clearly point at this chemokine as an important player in tumor progression and a possible novel prognostic marker for CCA.…”