Chemokine profiling in serum from patients with ovarian cancer reveals candidate biomarkers for recurrence and immune infiltration

Abstract

The management of advanced ovarian cancer is challenging due to the high frequency of recurrence, often associated with the development of resistance to platinum-based chemotherapy. Molecular analyses revealed the complexity of ovarian cancer with particular emphasis on the immune system, which may contribute to disease progression and response to treatment. Cytokines and chemokines mediate the cross-talk between cancer and immune cells, and therefore, present as potential biomarkers, reflecting the tumor microenvironment. A panel of circulating C-C motif chemokine ligand (CCL) and C-X-C motif chemokine ligand (CXCL) chemokines were examined in the serum of 40 high-grade patients with ovarian cancer prior to primary surgery. The level of immune infiltration in tumors was also analyzed. The preoperative levels of chemokines differ between patients. Elevated levels of circulating CXCL4 + CCL20 + CXCL1 combination can discriminate patients with shorter recurrence-free survival and overall survival. The presence of tumor-infiltrating T lymphocytes was detected in half of the patients. The mRNA expression analysis suggests the presence of antitumoral and immunosuppressive elements in the tumor microenvironment. The combination of circulating CXCL9 + CXCL10 can distinguish immune-infiltrated tumors that will lead to shorter recurrence-free survival. The results suggest that preoperative profiling of circulating chemokines in patients with ovarian cancer may provide valuable information regarding tumor recurrence and immune infiltration. The findings demonstrate that combinations have better prognostic utility than single chemokines, and may serve as patient stratification tools.

Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer

“…To establish proof-of-principle for the use of ART to discriminate between benign vs malignant disease, we measured active vs total CXCL10 concentrations in ascitic fluid harvested from patients with either benign or malignant ovarian tumours (Table 2). Consistent with prior studies [14,22], total CXCL10 was elevated in malignant (853.1 ± 1574.0 pg mL −1 ) compared with benign (160.8 ± 362.0 pg mL −1 ) ascites fluid (Figure 4A). Similarly, a broad range in active CXCL10 measurement was also observed (240.4 ± 410.5 pg mL −1 and 818.6 ± 1098.0 pg mL −1 , respectively) (Figure 4B).…”

SNHG22 overexpression indicates poor prognosis and induces chemotherapy resistance via the miR-2467/Gal-1 signaling pathway in epithelial ovarian carcinoma

“…Epithelial ovarian carcinoma (EOC) is the most common gynecological cancer and the fifth leading cause of cancer-related deaths in women [1]. The poor prognosis results from its high recurrence following curative resection, distant metastasis, and resistance to systemic chemotherapy [2–4]. Cisplatin and paclitaxel-based chemotherapies are first-line treatment regimens for most advanced and relapsed EOC patients; however, primary and secondary resistance to these therapeutics have been a major obstacle in EOC therapy [3, 5, 6].…”

Identification of CXCL10-Relevant Tumor Microenvironment Characterization and Clinical Outcome in Ovarian Cancer

“…Meanwhile, the chemokine landscape of ovarian cancer was found to be quite heterogeneous, because of different functions of known lymphocyte-recruiting chemokines in TME, such as CCL2, CXCL9, CXCL10, CXCL12, and CXCL16 (Arnold et al, 2005;Zsiros et al, 2015;Lieber et al, 2018). Notably, CXCL10 is an important lymphocyte chemoattractant to mediate the cross-talk between cancer and immune cells (Zsiros et al, 2015;Mlynska et al, 2019). Consistent with the previous studies, CXCL10-positive tumors had higher antigen processing, antitumor immune response, and TIL accumulation (Au et al, 2017;Theodoraki et al, 2018;Unger et al, 2018), thereby suggesting that CXCL10 expression is a predictive biomarker to evaluate immune cell infiltration in ovarian cancer TME.…”