Gas6在浸润性乳腺癌中的表达及其与临床病理特征和预后相关性研究

Background  Targeted drugs for the AXL/Gas6 signaling pathway have become a new focus in current cancer drug research. Howeverthere is significant controversy over the expression and role of Gas6 in breast cancer.Objective  To investigate the expression of Gas6 and AXL in breast cancer and to explore the correlation of GAS6 with clinicopathological features and prognosis. Methods  A total of 60 patients with invasive breast cancer who were treated at the Breast Surgery Department of Fujian Medical University Affiliated Mindong Hospital from October 2019 to February 2022 were included. Surgical resection specimens of cancerous and adjacent tissues were collected from these patients. The expressions of Gas6 and AXL were detected using immunohistochemical stainingIHC and real-time fluorescence quantitative PCR. Spearman correlation analysis was employed to assess the correlation between the two factors and the relationship between Gas6 and clinical pathological features. Additionallygene expression data for Gas6 and AXL in breast cancer and normal breast tissues were collected from the GEPIA2.0UALCANand METABRIC databases for supplementary validation. Survival data for different breast cancer subtypes were collected from the METABRIC dataset and KM Plotter database. Kaplan-Meier survival curve analysis was conducted to evaluate the correlation between Gas6 and breast cancer prognosis. Results  IHC and RT-qPCR detection results show that the relative expression levels of Gas6 protein and mRNA in breast cancer tissues are lower than those in adjacent non-cancerous tissueswith statistical significanceP<0.001. In contrastthe relative expression levels of AXL protein and mRNA in breast cancer tissues are higher than those in adjacent non-cancerous tissuesalso with statistical significanceP<0.001. Bioinformatics analysis reveals that there was a positive correlation between Gas6 and AXL mRNA expression in the total breast cancer population and four subtypes of patientsrs=0.460P<0.001. Moreoverstatistically significant differencesP<0.05 were observed in Gas6 mRNA expression levels among patients with different breast cancer molecular subtypesprimary tumor stageshistological gradeschemotherapy treatments and regional lymph node stages.Kaplan-Meier survival curve analysis indicates that in the overall breast cancer population and among patients with Luminal A subtypethe group with high Gas6 mRNA expression in cancerous tissues has a longer overall survival and disease-free survival compared to the low expression group. Additionallyfor Luminal B subtype patientsthe disease-free survival of the high Gas6 mRNA expression group in cancerous tissues is also longer than that of the low expression groupwith these differences being statistically significantP<0.05.Conclusion  High expression of tumor cell-derived Gas6 is a favorable prognostic factor for invasive breast cancer. Targeting Gas6 and its receptor in breast cancer represents a promising therapeutic approachparticularly when combined with immunotherapy.