Elevated levels of CA125 (MUC16) in metastatic gastric cancer as a strong predictor of poor survival

Introduction: CA125 is an extracellular domain of MUC16 glycoprotein. The clinical significance of serum CA125 has been most extensively studied in ovarian cancer. The significance of serum CA125 in gastric cancer has not been fully elucidated. There is evidence that MUC16 overexpression is associated with poor survival in patients with metastatic gastric cancer. We have not found any research papers on the correlation between the levels of serum CA125 and MUC16 overexpression.

Objective: The objective of the study was to assess the effects of elevated CA125 levels in patients with metastatic cancer on the long‑term results (time to disease progression and overall survival).

Materials and methods: CA125 was determined in the serum before the start of first‑line chemotherapy in 75 patients (45 males and 30 females) with metastatic gastric cancer. The mean age of the patients was 61,3 (26,7–84,9) years. Synchronous metastases were observed in 85 % of patients: 57,3 % in the peritoneum, 37,3 % in the liver, 5,4 % at other sites. Palliative gastrectomy and metastasectomy were performed in 28 % and 20 % of patients, respectively. Monotherapy, doublet and triplet chemotherapy regimens were used in 6,7 %, 58,7 % and 36,0 % of patients, respectively.

Results: the analysis showed that elevated levels of CA125 (> 37 IU/mL) were associated with a significant reduction in median time to progression (3,5 months (CI 2,87–9,53) vs 6,2 months, р = 0.001 (CI 2,02–4,9)) and overall survival (5,1 months (CI 6,07–28,1) vs 17,1 months (CI 3,5–6,67), р = 0.001). One‑factor ANOVA showed that factors with the strongest effects on the survival rates included the location of metastases (peritoneum), tumor histology (adenocarcinoma/signet ring cell carcinoma), the use of palliative gastrectomy and metastasis resection. A multi‑factor ANOVA showed that the only favorable prognostic factors in terms of overall survival rates were normal CA125 levels (HR 0,39 (95 % CI 0,18–0,84), р = 0.001) and the use of palliative gastrectomy (HR 0,23 (95 % CI 0,1–0,58), р = 0.001). The use of triplet chemotherapy regimens allowed to slightly improve the overall survival rates in the group of patients with elevated CA125 levels; however, the differences were not statistically significant (6,7 months vs 4Ю0 months, p = 0.29).

Conclusion: Elevated levels of CA125, which reflect MUC16 overexpression to a certain extent, is a strong independent predictor of poor outcome in metastatic gastric cancer. Currently, a possible way to overcome this negative impact is to use more intensive chemotherapy regimens. However, further research should be aimed at finding adequate targets and ways of neutralizing the negative impact of MUC16 overexpression in patients with metastatic gastric cancer.

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