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. 2019 Nov 25;19(1):1140.
doi: 10.1186/s12885-019-6321-x.

CYR61, a potential biomarker of tumor inflammatory response in epithelial ovarian cancer microenvironment of tumor progress

Jun Shi  1   2 , Rongfen Huo  3 , Ningli Li  3 , Haichuan Li  3 , Tianhang Zhai  3 , Huidan Li  3 , Baihua Shen  3 , Jing Ye  1   2 , Ruojin Fu  1   2 , Wen Di  4   5
Affiliations

CYR61, a potential biomarker of tumor inflammatory response in epithelial ovarian cancer microenvironment of tumor progress

Jun Shi et al. BMC Cancer. .

Abstract

Background: Recent studies have found that inflammatory response is involved in the pathogenesis of ovarian cancer. Advanced ovarian cancer is often presented with ascites that is rich in cytokines, inflammatory factors or cancer cells. Therefore, it is important to study the microenvironment of ascites in order to further clarify the occurrence and progression of ovarian cancer. As a pro-inflammatory factor, the Cyr61 expression patterns are inconsistent in human tumors. Although it has been reported that Cyr61 is related to the progression of ovarian cancer, its specific mechanism is not yet clear. This study sought to evaluate the Cyr61 levels of ascites, serum and different tissues of ovarian cancer to explore the potential association of Cyr61with the tumor-associated inflammatory microenvironment of EOC.

Methods: Tumor specimens were procured from patients with ovarian serous cystadenocarcinoma and ovarian serous cystadenoma. Cyr61 and IL-6 levels of serum or ascites were determined by ELISA (Enzyme-Linked ImmunoSorbent Assay), while Cyr61 expressions of different ovarian tumor tissues were evaluated by IHC (Immunohistochemistry). Then the correlation of Cyr61 level in ascites with clinicopathologic features was analyzed. And other laboratory data were obtained from medical records.

Results: Both in ascites and serum, significantly higher Cyr61 levels were found in ovarian serous cystadenocarcinoma. In malignant ascites, higher Cyr61 level of ovarian serous cystadenocarcinoma was more closely associated with FIGO stage, initial tumor size > 10 cm and the residual tumor size. And the increased IL-6 level was linearly related to Cyr61 level. Moreover, the serum levels of Cyr61, IL-6 and CRP in advanced stage of ovarian cancer were much higher than those in early stage. Lastly, the IHC data demonstrate that Cyr61 expression of ovarian serous adenocarcinoma was higher than that of ovarian serous cystadenoma, but it was lower than the paired metastatic lesions.

Conclusions: As a pro-inflammatory factor, increased ascites Cyr61 level is associated with FIGO stage, initial tumor size > 10 cm and the residual tumor size. Moreover, serum Cyr61 may be used as a potential marker for EOC inflammatory response. Finally, Cyr61 may be involved in the process of tumor metastasis and progression by producing IL-6 and CRP in the EOC inflammatory microenvironment.

Keywords: Cyr61; Epithelial ovarian cancer; Tumor progression; Tumor-associated inflammatory microenvironment.

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Conflict of interest statement

The authors declare that they have no competing interests .

Figures

Fig. 1
Fig. 1
Expression levels of Cyr61 in ascites and serum of ovarian benign and malignant tumor Cyr61 levels in ascites and serum of ovarian serous adenocarcinoma patients (n = 66) were significantly higher than those of ovarian serous cystadenoma patients (n = 18). And the ascites Cyr61 level was much higher than that of serum
Fig. 2
Fig. 2
Cyr61 and IL-6 levels in ascites of different (the early or advanced) stage of ovarian cancer patient and the correlation. In the patient with ovarian serous adenocarcinoma, ascites Cyr61 and IL-6 levels of the advanced stage (n = 52) were both higher than those of the early stage (n = 14). And the increased IL-6 expression was linearly related to Cyr61 level in malignant ascites
Fig. 3
Fig. 3
Cyr61 expression patterns in the different tissues of ovarian tumor by immunohistochemistry. a Benign ovarian cyst (ovarian serous cystadenoma) showed weak Cyr61 expression. b High grade of ovarian serous adenocarcinoma showed moderate degree Cyr61 expression. c and d High grade of ovarian serous adenocarcinoma of the same patient of primary and paired metastatic site showed the moderate and strong degree Cyr61 expression, respectively
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