To investigate the expression of SPOCK2 gene in ovarian cancer and its clinical significance.

The online software Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the expression of SPOCK2 mRNA in ovarian cancer tissues. The online software Human Protein Atlas was used to analyze the expression of SPOCK2 protein in ovarian cancer tissues, and the online software UALCAN was used to analyze the expression of SPOCK2 mRNA in ovarian cancer tissues with different degrees of differentiation. The online software GEPIA was used to determine the optimal cut-off value of SPOCK2 mRNA expression in patients with ovarian cancer. According to the optimal cut-off value, the samples from these patients were divided into the high expression group and low expression group, with generation of a survival curve. The online software TIMER was used to examine the type of ovarian cancer infiltrating cells and the extent of infiltration. The correlation between SPOCK2 mRNA expression, the type of ovarian cancer infiltrating cells and the extent of infiltration was determined. The online software SurvivalMeth was used to analyze the methylation of SPOCK2 and its correlation with the prognosis of ovarian cancer.

The online softwares GEPIA and The Human Protein Atlas, showed that, compared with normal or adjacent tissues, SPOCK2 mRNA and protein were highly expressed in ovarian cancer tissues (both P<0.05) . In ovarian cancer tissues with different degrees of differentiation, higher level of SPOCK2 mRNA expression was associated with lower differentiation degree of ovarian cancer cells. Survival curve analysis showed that SPOCK2 mRNA expression was significantly correlated with survival rate, and the overall survival time was significantly lower in SPOCK2 mRNA high expression group than that in low expression group (P<0.01) . The 5-year survival rate of patients in the SPOCK2 mRNA high expression group was only 22%, compared with 39% in the low expression group was 39%. The SPOCK2 mRNA expression level was negatively correlated with the infiltration of Th1, Th2, CD4⁺ memory T cells, and M1 macrophages (r=-0.135, -0.214, -0.205, and -0.147, all P<0.05) , and was positively correlated with tumor-associated macrophage infiltration (r=0.289, P<0.01) . Testing with two DNA methylation probes showed that the methylation level of SPOCK2 in ovarian cancer tissues was lower than that in normal tissues (P<0.01) . Survival analysis showed significant difference in survival rate between patients with high-risk and low-risk of ovarian cancer, and lower level of SPOCK2 methylation in ovarian cancer tissues of the high-risk patients (both P<0.05) .

SPOCK2 is highly expressed in ovarian cancer and promotes the progression of ovarian cancer. Therefore it may be a potential prognostic indicator and therapeutic target for ovarian cancer.

Ovarian Cancer; SPOCK2 gene; DNA methylation; Immune infiltrating cells