免疫组化联合生物信息学分析信号转导与转录激活因子1在乳腺癌中的表达及与临床病理特征的关系-东南大学学报医学版

免疫组化联合生物信息学分析信号转导与转录激活因子1在乳腺癌中的表达及与临床病理特征的关系

单位：秦皇岛市妇幼保健院乳腺科, 河北秦皇岛 066000

分类号：R737.9

出版年·卷·期（页码）：2025·44·第二期（205-211）

摘要：

目的:探究乳腺癌(BC)中信号转导与转录激活因子1(STAT1)的表达情况,并评估其在BC诊断和预后中的预测价值。方法:分别利用免疫组化和TCGA-BC数据研究STAT1在BC组织中的表达,使用受试者工作特征(ROC)曲线评估STAT1在BC中的诊断价值,通过Kaplan-Meier生存分析和Cox回归分析研究STAT1的表达与BC患者预后的关系。结果:在肾上腺皮质癌(ACC)、膀胱尿路上皮癌(BLCA)、BC等 33 种癌症类型中,STAT1 在大多数肿瘤组织中的表达高于正常组织,呈现上调状态。针对BC进一步分析,从 TCGA 数据集中获取 1 113 例 BC 患者样本和 113 例正常样本进行非配对分析,结果显示,BC组织中 STAT1 的表达显著高于正常组织(P＜0.05)。进行配对分析时,对比 TCGA 数据库中配对的 BC 与癌旁正常组织,同样显示BC组织中 STAT1 的表达显著上调(P＜0.05)。随着肿瘤 T 分期和 N 分期的增加,STAT1 的表达量逐渐增加。ROC 曲线分析显示,STAT1 在BC诊断中的曲线下面积(AUC)为 0.768(基于 TCGA 数据库 mRNA 表达)和 0.970(基于免疫组化检测蛋白表达),具有较高可靠性。Kaplan-Meier 生存分析显示,STAT1 高表达与BC患者不良预后相关(mRNA 高表达时,P=0.011;蛋白高表达时,P=0.036)。亚组分析表明,高 STAT1 表达显著影响 N0/N1(P=0.005)和 T1/T2(P=0.019)分期BC患者的总生存期。免疫组化结果显示,BC组织中 STAT1 阳性表达 45 例,阴性表达 41 例,邻近非肿瘤组织中 STAT1 阳性表达 31 例,阴性表达 55 例(χ²=4.621,P<0.001),进一步验证了 STAT1 在BC细胞中的促癌作用。临床病理特征分析显示,高 STAT1 组患者表现出更高的 T 分期(P=0.033)、N 分期(P=0.034)和 ER 阳性特征(P=0.020)。多因素 Cox 回归分析结果显示,STAT1 高表达是BC患者的独立预后危险因素(P＜0.05)。结论: STAT1在BC中的高表达可能参与了肿瘤的发生和发展,并且具有作为BC的潜在诊断和预后标志物的潜力。

Objective: To investigate the expression of signal transducer and activator of transcription 1(STAT1) in breast cancer(BC) and evaluate its predictive value in diagnosis and prognosis. Methods: Immunohistochemistry and TCGA-BC data were used to study STAT 1 expression in BC tissues, receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of STAT 1 in BC. In addition, the relationship between STAT 1 expression and the prognosis of BC patients was further investigated by Kaplan-Meier survival analysis and Cox regression analysis. Results: In 33 types of cancers, including adrenocortical carcinoma(ACC), bladder urothelial carcinoma(BLCA), BC, and others, the expression of STAT1 in the tumor tissues of most cancer types was higher than that in normal tissues, showing an upregulated state.Further analysis of BC was conducted by retrieving 1 113 BC patient samples and 113 normal samples from the TCGA dataset for unpaired analysis. The results showed that the expression of STAT1 in BC tissues was significantly higher than that in normal tissues(P<0.05). When paired analysis was performed, comparing the paired BC and adjacent normal tissues in the TCGA database, the expression of STAT1 in BC tissues was also significantly upregulated(P<0.05). With the increase in tumor T and N stages, the expression level of STAT1 gradually increased. ROC curve analysis indicated that the area under the curve(AUC) for STAT1 in breast cancer diagnosis was 0.768(based on TCGA database mRNA expression) and 0.970(based on immunohistochemical detection of protein expression), showing high reliability. Kaplan-Meier survival analysis showed that high expression of STAT1 was associated with poor prognosis in BC patients(P=0.011 for high mRNA expression; P=0.036 for high protein expression). Subgroup analysis indicated that high STAT1 expression significantly affected the overall survival of patients with N0/N1(P=0.005) and T1/T2(P=0.019) BC. Immunohistochemical results showed that among breast cancer tissues, 45 cases were positive for STAT1 expression and 41 cases were negative, while among adjacent non-tumor tissues, 31 cases were positive and 55 cases were negative for STAT1 expression(χ²=4.621, P<0.001), further validating the oncogenic role of STAT1 in BC cells. Clinical pathological feature analysis showed that patients in the high STAT1 group exhibited higher T stages(P=0.033), N stages(P=0.034), and ER-positive characteristics(P=0.020). Multivariate Cox regression analysis results showed that high expression of STAT1 was an independent prognostic risk factor for BC patients(P<0.05). Conclusion: The findings of this study suggest that the high expression of STAT1 in BC may be involved in tumor initiation and progression, and it has the potential to serve as a diagnostic and prognostic marker for breast cancer.

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