The expression of MAP4K4 and HIF2α in peripheral blood of patients with locally advanced cervical cancer is correlated with excessive activation of autophagy and sensitivity to platinum-based neoadjuvant chemotherapy

Article ID: 4896

Abstract

Objective: To investigate the expression of mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) and Hypoxia-inducible factor 2α(hypoxia-inducible factor 2α) in peripheral blood of patients with locally advanced cervical cancer The relationship between the expression of HIF 2α and the over-activation of autophagy and sensitivity to platinum-based neoadjuvant chemotherapy in cervical cancer patients. Methods: A total of 230 patients with locally advanced cervical cancer admitted to our hospital from August 2022 to August 2025 were prospectively selected as the research objects. The expressions of MAP4K4, HIF2α and autophagy-related genes [LC-3Ⅱ, LC-3I and Beclin-1] in peripheral blood before and after chemotherapy were detected by qRT-PCR. Pearson test was used for correlation analysis. Logistic regression model was used to analyze the independent risk factors of chemotherapy sensitivity. Results: MAP4K4 and HIF2α were expressed in peripheral blood of patients with locally advanced cervical cancer in the subgroups of age, tumor size and histological type (P > 0.05), while MAP4K4 and HIF2α were expressed in the subgroups of differentiation, FIGO stage and lymph node metastasis (P <0.05). Before chemotherapy, MAP4K4 mRNA and HIF2α mRNA in peripheral blood were compared between the two groups (P > 0.05). After chemotherapy, two groups of MAP4K4 mRNA, HIF2 alpha mRNA were significantly lower (P < 0.05), and effective group MAP4K4 mRNA, HIF2 alpha mRNA significantly below invalid group (P < 0.05); Before chemotherapy, LC-3Ⅱ, LC-3I and Beclin-1 were compared between the two groups (P > 0.05); After chemotherapy, LC-3Ⅱ, LC-3I and Beclin-1 in the two groups were increased, and LC-3Ⅱ, LC-3I and Beclin-1 in the ineffective group were significantly higher than those in the effective group (P <0.05). MAP4K4 and HIF2α were positively correlated with LC-3Ⅱ, LC-3I and Beclin-1 (P <0.05). The degree of differentiation, FIGO stage, lymph node metastasis, LC-3Ⅱ, LC-3I, Beclin-1, MAP4K4 and HIF2α were independent risk factors for chemotherapy sensitivity in patients with locally advanced cervical cancer (P <0.05). Conclusions: MAP4K4 and HIF2α are up-regulated in patients with locally advanced cervical cancer, which are closely related to the excessive activation of autophagy during chemotherapy and the sensitivity to platinum-based neoadjuvant chemotherapy.