Salt-inducible kinase 3 expression identifies long-term survivors of serous ovarian cancer

[[abstract]]Background: Epithelial ovarian cancer (EOC) has a high tumor-associated mortality rate among the gynecological cancers because EOC is usually diagnosed during the advanced stage. Cancer antigen (CA) 125 is the most well-studied biomarker for ovarian cancer screening. However, CA125 is also elevated in numerous conditions, resulting in decreased specificity. Materials and Method: We collected ovarian cancer specimens from 204 patients and examined the SIK3 and CA125 expression levels. The expression percentage of SIK3 or CA125 in the tumor cells, pre-surgery serum CA125 was divided into two groups and compared with patient overall survival, progression-free survival, cancer stage, cancer type and chemotherapeutic resistance. Results: A total of 30.9% of the patients had stage I disease, 7.8% had stage II disease, 52.4% had stage III disease, and 8.9% had stage IV disease. The median OS and PFS were 49.5 months (range 0.25-205 months) and 28.4 months (0.25-182.4), respectively. The mean age of the patients was 52.8 years (range 25-82 years). The histological classification was based on the four main ovarian cancer types: serous (51.5%), endometrioid (14.2%), clear cell (20.6%), and mucinous (9.3%). In all stages of the disease, high expression of SIK3 (SIK3-H) was associated with a markedly better OS, compared with low expression of SIK3 (SIK3-L) (127.0 months and 46.0 months, respectively; hazard ratio [HR] for death, 0.59; 95% confidence interval [CI], 0.41 to 0.86; P=0.005). SIK3-H had a markedly better PFS rate than SIK3-L (66.0 months and 26.0 months, respectively; HR for disease progression or recurrence, 0.68; 95% CI, 0.47 to 0.99; P=0.04). The same results were evident for serous ovarian cancer, where SIK3-H had a better OS rate than SIK3-L (75.0 months and 34.0 months, respectively; HR for death, 0.57; 95% CI, 0.36 to 0.91; P=0.02) and a better PFS rate than SIK3-L (44 and 13 months, respectively; HR, 0.52; 95% CI, 0.32 to 0.83; P=0.006). Notably, for advanced stage serous ovarian cancer, Only SIK3-H had a better OS rate than SIK3-L (48.0 months and 28.0 months, respectively; HR for death, 0.56; 95% CI, 0.33 to 0.96; P=0.03) and PFS rate (32 and 13 months, respectively; HR, 0.57; 95% CI, 0.34 to 0.95; P=0.03). Tissue CA125 expression and the pre-surgery serum CA125 level did not show significant differences in OS and PFS. Our results demonstrated that high SIK3 expression correlated with better OS and PFS rates in ovarian cancer patients, especially in patients with advanced serous ovarian cancer. Conclusion: High expression of SIK3 indicates a better prognosis in primary ovarian cancer and serous disease, especially in advanced serous disease