血清IL-12及IFN-γ在乳腺癌新辅助化疗疗效评估中的研究

Evaluation of Efficacy of Serum IL-12 and IFN-γ in Neoadjuvant Chemotherapy for Breast Cancer

摘要: 目的：利用生信分析探讨细胞因子IL-12及IFN-γ对乳腺癌患者免疫微环境的影响，并结合临床病理特征，对其评估新辅助化疗疗效的价值进行研究。方法：在基因表达综合(GEO)数据库中下载GSE163882，比较IL-12相对应基因IL12B及IFN-γ相对应基因IFNG在病理完全缓解(pCR)患者和残留病灶(RD)患者中的表达。收集于我院接受新辅助化疗的50例乳腺癌患者的临床资料，使用卡方检验分析临床病理特征与新辅助化疗疗效的相关性；通过ROC曲线评估血清IL-12、IFN-γ的预测价值，并且确定最佳截断值；采用二元Logistic回归进行多因素分析。通过ssGSEA免疫浸润分析IL12B和IFNG与免疫细胞浸润的相关性；采用GO和KEGG功能富集分析，探讨相关基因潜在生物学功能及信号通路。结果：在GEO数据库GSE163882数据集中IL12B和IFNG在pCR患者中呈现高表达。于我院收治的临床患者中pCR患者化疗前血清IL-12和IFN-γ水平明显高于非pCR组(P < 0.05)；单因素分析显示，新辅助化疗后pCR与腋窝淋巴结转移、PR表达、Her-2表达及血清IL-12和IFN-γ表达状态显著相关(P < 0.05)；多因素Logistic分析显示，化疗前血清IFN-γ水平是新辅助化疗疗效的独立影响因素。免疫浸润分析显示，活化CD4 T细胞、活化CD8 T细胞、活化B细胞和自然杀伤细胞在pCR患者中高度浸润。结论：血清IL-12和IFN-γ表达状态与新辅助化疗效果具有相关性，化疗前血清IFN-γ高表达是pCR的独立预测因子。

Abstract: Objective: To investigate the effects of cytokines IL-12 and IFN-γ on the immune microenvironment of breast cancer patients by means of Bioinformatics analysis, and to study their value in evaluating the efficacy of neoadjuvant chemotherapy combined with clinicopathological characteristics. Methods: GSE163882 was downloaded from the Gene Expression Omnibus database, and the expressions of IL-12 corresponding gene IL12B and IFNG corresponding gene IFN-γ were compared in pathologic complete response patients and residual lesion patients. The clinical data of 50 breast cancer patients who received neoadjuvant chemotherapy at The Affiliated Hospital of Qingdao University were collected. Chi-square test was used to analyze the correlation between clinicopathological features and the efficacy of neoadjuvant chemotherapy. The predictive value of serum IL-12 and IFN-γ was evaluated by ROC curve. Multivariate analysis was performed by binary Logistic regression. The correlation between IL12B and IFNG and immune cell infiltration was analyzed by ssGSEA immunoinfiltration. GO and KEGG functional enrichment analysis were used to explore the potential biological functions and signaling pathways of related genes. Results: IL12B and IFNG were highly expressed in pCR patients in the GSE163882 dataset. The serum levels of IL-12 and IFN-γ in pCR patients before chemotherapy were significantly higher than those in non-PCR group (P < 0.05). Univariate analysis showed that pCR was significantly correlated with axillary lymph node metastasis, PR expression, Her-2 expression and serum IL-12 and IFN-γ expression after neoadjuvant chemotherapy (P < 0.05). Multivariate Logistic analysis showed that serum IFN-γ level before chemotherapy was an independent factor influencing the efficacy of neoadjuvant chemotherapy. Immunoinfiltration analysis showed that activated CD4 T cells, activated CD8 T cells, activated B cells, and natural killer cells were highly infiltrated in pCR patients. Conclusion: The expression of serum IL-12 and IFN-γ is correlated with the effect of neoadjuvant chemotherapy, and the high expression of serum IFN-γ before chemotherapy is an independent predictor of pCR.