Application of serum annexin A3 combined with hypoxia-inducible factor-1α in the prediction of platinum resistance in colorectal cancer

Objective To investigate the relationships between the expression of peripheral blood annexin A3 (ANXA3), hypoxia-inducible factor-1α (HIF-1α) and platinum resistance in colorectal cancer.

Methods Clinical data of 122 patients with colorectal cancer treated with platinum-based chemotherapy were retrospectively analyzed. Drug resistance was evaluated after 6 cycles of chemotherapy, and patients were divided into drug resistant group (48 cases) and sensitive group (74 cases) according to their sensitivity to platinum drugs. the clinical data and the levels of ANXA3 and HIF-1α in peripheral blood of the two groups were compared; Logistic regression model was used to analyze the influencing factors of platinum resistance; the receiver operating characteristic (ROC) curve was drawn to analyze the predictive efficacy of ANXA3 and HIF-1α in peripheral blood on platinum-based drug resistance.

Results There were no significant differences in sex composition, age, TNM stage and histological grade between the drug resistant group and sensitive group (P > 0.05). ANXA3 and HIF-1α levels in peripheral blood of the drug resistant group were significantly higher than those in the sensitive group (P < 0.05). The median progression free survival (PFS) of patients in the drug resistant group was 20.5 months (95%CI, 16.744 to 30.254), and the median PFS of patients in the sensitive group was 30.4 months (95%CI, 23.617 to 34.569). The median PFS of the drug resistant group was significantly shorter than that of the sensitive group (P < 0.05). ROC curve showed that the area under the curve (AUC) for predicting platinum resistance was 0.847 when 2.03 mg/L was the cut-off value; when HIF-1α was truncated at 189.57 pg/mL, the predicted AUC of platinum resistance was 0.722. The AUC of platinum resistance predicted by ANXA3 was significantly larger than that of HIF-1α(Z=2.201, P < 0.05). The AUC of ANXA3 combined with HIF-1α was 0.915, which was significantly larger than that of ANXA3 and HIF-1α alone (Z=2.150, 3.021, P < 0.05). Compared with ANXA3, ANXA3 combined with HIF-1α showed higher sensitivity in predicting platinum resistance; compared with HIF-1α, ANXA3 combined with HIF-1α had higher specificity in predicting platinum resistance.

Conclusion High levels of ANXA3 and HIF-1α in peripheral blood are closely related to platinum-resistance in colorectal cancer. The combination of ANXA3 and HIF-1α shows high predictive efficacy in the determination of platinum-type drug resistance in colorectal cancer.