IGHG1和TMSB10蛋白表达与HER2阳性乳腺癌新辅助治疗效果及预后的关系

doi:10.3969/j.issn.1004-616x.2026.02.009

摘要/Abstract

摘要： 目的： 探讨免疫球蛋白重链1(IGHG1)和胸腺素β10(TMSB10)蛋白表达与人类表皮生长因子受体2(HER2)阳性乳腺癌新辅助治疗(NAT)后病理完全缓解(pCR)率及Miller-Payne(MP)分级反应的相关性，并评估其对患者预后的预测价值。方法： 从GEO数据库的NAT数据集GSE243375中获取242个HER2阳性乳腺癌病例数据，通过差异表达分析、LASSO回归与支持向量机递归特征消除(SVM-RFE)筛选与pCR相关的差异基因。收集108例HER2阳性且接受NAT的乳腺癌患者病理组织蜡块及临床病理资料，采用免疫组织化学法检测肿瘤组织中IGHG1和TMSB10蛋白表达水平。采用卡方检验分析两者表达与临床病理特征的相关性；Mann-Whitney U检验比较pCR组与非pCR组间蛋白表达水平的差异；Spearman秩相关分析评估其表达与MP分级的相关性。进一步采用二元Logistic回归和有序Logistic回归校正混杂变量，分析IGHG1和TMSB10对pCR和MP分级的独立预测价值。结果： 生物信息学分析筛选出了10个与HER2阳性乳腺癌NAT后pCR相关的差异基因，IGHG1和TMSB10预测pCR的曲线下面积(AUC)分别为0.626和0.618。免疫组织化学染色结果显示，TMSB10主要表达于乳腺癌肿瘤细胞胞浆，呈棕黄色颗粒状着色；IGHG1主要表达于乳腺癌肿瘤细胞胞浆，呈弥漫或灶状棕黄色颗粒，偶见胞膜阳性表达。单因素分析显示，TMSB10在pCR组表达显著高于非pCR组(P=0.038)，且IGHG1高表达在p CR组的比例(15.3%)亦显著高于非pCR组(2.0%)(P=0.043)。多因素Logistic回归分析显示，TMSB10是MP分级的独立预测因素[OR=1.232,95%CI(1.060,1.431),P=0.006],IGHG1亦是MP分级的独立预测因素[OR=1.434,95%CI(1.028,2.000),P=0.034]。二者联合预测pCR的AUC值为0.660[95%CI(0.557,0.763)]，优于单一指标。结论： IGHG1是HER2阳性乳腺癌NAT后MP分级升高的独立预测因素，且其高表达与更高的pCR率显著相关；TMSB10是pCR和MP分级升高的独立预测因素。IGHG1和TMSB10联合应用可提高预测HER2阳性乳腺癌NAT疗效的准确性。

关键词: 乳腺癌, 新辅助治疗, 免疫球蛋白重链1, 胸腺素β10

Abstract: OBJECTIVE: To investigate correlations between protein expression of immunoglobulin heavy constant gamma 1(IGHG1) and thymosin β10(TMSB10) with pathological complete response(p CR) and Miller-Payne(MP) grading following neoadjuvant therapy(NAT) in patients with human epidermal growth factor receptor 2(HER2)-positive breast cancer, and to evaluate their predictive value. METHODS: Data of 242 HER2-positive breast cancer cases were obtained from the NAT dataset GSE243375 in the GEO database.Differentially expressed genes related to p CR were screened through differential expression analysis, LASSO regression,and support vector machine recursive feature elimination(SVM-RFE). Pathological tissue paraffin blocks and clinicopathological data were collected from 108 HER2-positive breast cancer patients who received NAT. The chi-square test was used to analyze correlations between expression of these two proteins and clinicopathological characteristics. The Mann-Whitney U test was employed to compare differences in protein expression levels between the p CR group and the non-pCR group. Spearman rank correlation analysis was performed to evaluate correlations between their expression and MP grade. Furthermore,binary logistic regression and ordinal logistic regression were used to adjust for confounding variables and to analyze independent predictive values of IGHG1 and TMSB10 for p CR and MP grade. RESULTS: Bioinformatics analysis identified 10 differentially expressed genes related to p CR after NAT in HER2-positive breast cancer. The AUC values for predicting p CR by IGHG1 and TMSB10 were0.626 and 0.618, respectively. Immunohistochemical results showed that TMSB10 was mainly expressed in the cytoplasm of breast cancer tumor cells,presenting brown-yellow granular staining. IGHG1 was mainly expressed in the cytoplasm of breast cancer tumor cells, showing diffuse or focal brown-yellow granular staining, with occasionally positive expression on the cell membrane. Univariate analysis revealed that expression levels of TMSB10 were significantly higher in the p CR group than in the non-pCR group(P=0.038),and the proportion of IGHG1 high expression in the p CR group(15.3%) was also significantly higher than that in the non-pCR group(2.0%)(P=0.043). Multivariate Logistic regression analysis showed that TMSB10 was an independent predictor of increased MP grade[OR=1.232,95%CI(1.060,1.431),P=0.006],and IGHG1 was also an independent predictor of increased MP grade[OR=1.434,95%CI(1.028,2.000),P=0.034]. The combined prediction AUC value for p CR by both indicators was 0.660 [95%CI(0.557,0.763)],which was superior to a single indicator. CONCLUSION: IGHG1 was shown to be an independent predictor of increased MP grade after neoadjuvant therapy in HER2-positive breast cancer,and its high expression was significantly associated with higher p CR rates. TMSB10 was an independent predictor of p CR and increased MP grade. IGHG1 and TMSB10 can be considered to be potential biomarkers for predicting efficacy of NAT in HER2-positive breast cancer. The combined application of IGHG1 and TMSB10 could improve accuracy of predicting the efficacy of NAT in HER2-positive breast cancer.

Key words: breast cancer, neoadjuvant therapy, IGHG1, TMSB10

中图分类号:

R737.9

孙雪, 黄诗禄, 焦纪伟, 廖勇, 邱前程, 洪良利. IGHG1和TMSB10蛋白表达与HER2阳性乳腺癌新辅助治疗效果及预后的关系[J]. 癌变·畸变·突变, 2026, 38(2): 142-149,155.

SUN Xue, HUANG Shilu, JIAO Jiwei, LIAO Yong, QIU Qiancheng, HONG Liangli. Relationship between expression of IGHG1 and TMSB10 proteins and neoadjuvant therapy efficacy in HER2-positive breast cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2026, 38(2): 142-149,155.

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