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Fractalkine (C-X3-C motif chemokine ligand 1) as a potential biomarker for depression and anxiety in colorectal cancer patients.

ABSTRACT: Fractalkine, a unique chemokine of the CX3C subfamily, is involved in the pathogenesis of different types of cancer and also in non-immune mechanisms associated with psychiatric disorders. The aim of the present study was to investigate whether there is a correlation between anxiety, depression and fractalkine serum levels in colorectal cancer (CRC) patients in different stages of antitumor therapy. Four groups of patients undergoing treatment (n=20 per group) were evaluated: Patients with CRC who did not undergo surgical resection of the tumor; patients who underwent resection and who did not start adjuvant therapy; patients undergoing chemotherapy for ~3 months; and patients who had completed adjuvant chemotherapy regimen for ~6 months. The control group was composed of 20 healthy volunteers free of any psychiatric or immune system disease. Depression and anxiety were evaluated using the Hospital Anxiety and Depression Scale (HADS) and serum levels of fractalkine were measured by cytometric bead array. Clinically relevant levels of anxiety and/or depression were observed in all of the CRC patients at the different stages of antitumor therapy. Elevated serum levels of fractalkine were identified in the CRC patients in the pre-surgery (P<0.001) and pre-chemotherapy (P<0.001) groups, but reduced upon chemotherapy (P<0.05). Furthermore, a positive correlation was observed between fractalkine levels and the HADS scores in the CRC patients at different stages of antitumor therapy. These results demonstrate a link between fractalkine, depression and anxiety in CRC patients indicating that this chemokine is involved in the pathophysiology of these comorbidities. An improved understanding of the molecular mechanisms involved in these psychological disorders will allow the design of novel therapeutic strategies to assist in alleviating such symptoms in cancer patients. Therefore, fractalkine may present as a relevant biomarker for depression and anxiety in CRC patients.

SUBMITTER: Miranda DO

PROVIDER: S-EPMC5525586 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:Background and aimsHepatocellular carcinoma (HCC) is an aggressive malignancy which is often associated with a complex tumor microenvironment attributable to etiology-induced cellular inflammation. γδ T cells are known to detect and react to chronic inflammation, which is linked to cancer development, progression, and metastasis. Our recent genomic study revealed an increased infiltration of several immune cell types, including γδ T cells, in tumor microenvironments of a Thai HCC subtype associated with a good prognosis.Approach and resultsHere, we quantified the amount of γδ T cells using a γδ T-cell-specific gene signature in 247 Chinese HCC patients. We also validated the γδ T-cell signature in American HCC patients. Additionally, such an association was only found in tumor transcriptomic data, but not in adjacent nontumor transcriptomic data, suggesting a selective enrichment of γδ T cells in the tumor microenvironment. Moreover, the γδ T-cell signature was positively correlated with the expression of natural killer cell receptor genes, such as NKG2D and cytolytic T-cell genes granzymes and perforin, suggesting a stronger T-cell-mediated cytotoxic activity. Furthermore, we found that the γδ T-cell-specific gene expression is positively correlated with the expression of chemokine (C-C motif) ligand 4 (CCL4)/chemokine (C-C motif) ligand 5 (CCL5) and C-C chemokine receptor type 1 (CCR1)/C-C chemokine receptor type 5 (CCR5), the receptors for γδ T cells. We validated these results using immunohistochemical analysis of formalin-fixed, paraffin-embedded tumor biopsies from 182 HCC patients. Moreover, we found evidence of CCL4/CCL5-mediated recruitment of γδ T cells both in vitro and in a murine orthotopic Hepa1-6 HCC model.ConclusionsWe propose that CCL4/CCL5 may interact with their receptor, CCR1/CCR5, which may facilitate the recruitment of γδ T cells from peripheral blood or peritumor regions to the tumor regions. Consequently, an increasing infiltration of γδ T cells in tumors may enhance antitumor immunity and improve patients' prognosis.

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Fractalkine (C-X3-C motif chemokine ligand 1) as a potential biomarker for depression and anxiety in colorectal cancer patients.

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