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

Abstract

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

CLC Number:

R737.9

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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Relationship between expression of IGHG1 and TMSB10 proteins and neoadjuvant therapy efficacy in HER2-positive breast cancer

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