血清中线粒体核糖体大亚基蛋白13/BCL2相关蛋白A1/TP53凋亡诱导蛋白1表达谱预测三阴性乳腺癌化疗应答的价值及其免疫调控机制

Value of expression profile of mitochondrial ribosomal large subunit protein 13/BCL2-related protein A1/TP53 apoptosis-inducing protein 1 in serum in predicting chemotherapy response of triple-negative breast cancer and its immune regulatory mechanism

  • 摘要:
    目的 探讨乳腺癌患者血清中线粒体核糖体大亚基蛋白13(MRPL13)、BCL2相关蛋白A1(BCL2A1)和TP53凋亡诱导蛋白1(TP53AIP1)mRNA表达水平与患者化疗疗效以及免疫功能的关系。
    方法 选取148例接受化疗的三阴性乳腺癌患者作为研究对象, 依据化疗疗效将其分为有效组(97例)和无效组(51例)。选取同期健康体检者60例作为对照组。检测患者血清MRPL13BCL2A1TP53AIP1 mRNA表达水平。检测患者血清中免疫球蛋白M(IgM)、免疫球蛋白G(IgG)和免疫球蛋白A(IgA)的浓度及全血中CD4+、CD8+细胞的比例。比较乳腺癌组与对照组的MRPL13BCL2A1TP53AIP1 mRNA表达水平。比较有效组与无效组患者的MRPL13BCL2A1TP53AIP1 mRNA表达水平。比较化疗前后有效组与无效组免疫功能指标的差异。分析MRPL13BCL2A1TP53AIP1 mRNA表达水平与免疫指标的相关性。筛选影响化疗疗效的因素。
    结果 乳腺癌组的MRPL13BCL2A1 mRNA表达水平高于对照组, TP53AIP1 mRNA表达水平低于对照组, 差异有统计学意义(P < 0.05)。有效组的MRPL13BCL2A1 mRNA表达水平低于无效组, TP53AIP1 mRNA表达水平高于无效组,差异有统计学意义(P < 0.05)。化疗后,有效组IgM浓度高于无效组,差异有统计学意义(P < 0.05)。有效组的CD8+比例低于无效组,差异有统计学意义(P < 0.05)。MRPL13 mRNA表达水平与IgM、IgG、CD8+呈正相关(r=0.672、0.716、0.824, P < 0.05)。BCL2A1 mRNA表达水平与IgA、CD4+呈正相关(r=0.654、0.862, P < 0.05)。TP53AIP1 mRNA表达水平与CD4+、CD8+呈负相关(r=-0.846、-0.792, P < 0.05)。MRPL13BCL2A1高表达是乳腺癌患者化疗疗效的独立危险因素(P < 0.05); TP53AIP1高表达则为保护因素(P < 0.05)。
    结论 三阴性乳腺癌化疗患者血清MRPL13BCL2A1TP53AIP1 mRNA表达水平与IgM、IgG、IgA及CD4+、CD8+ T细胞比例、化疗疗效相关。MRPL13BCL2A1高表达是化疗疗效不良的独立危险因素, 而TP53AIP1高表达为保护因素。

     

    Abstract:
    Objective To investigate the relationships of the mRNA expression levels of mitochondrial ribosomal large subunit protein 13 (MRPL13), BCL2-associated protein A1 (BCL2A1) and TP53 apoptosis-inducing protein 1 (TP53AIP1) in the serum of breast cancer patients with their chemotherapy efficacy as well as immune function.
    Methods A total of 148 triple-negative breast cancer patients undergoing chemotherapy were selected as the study subjects. Based on chemotherapy efficacy, they were divided into responsive group (97 cases) and non-responsive group (51 cases). Sixty healthy individuals undergoing physical examinations during the same period were selected as the control group. The mRNA expression levels of MRPL13, BCL2A1 and TP53AIP1 in the serum of patients were detected. The concentrations of immunoglobulin M (IgM), immunoglobulin G (IgG) and immunoglobulin A (IgA) in the serum of patients were measured, and the proportions of CD4+ and CD8+ cells in whole blood were determined. The mRNA expression levels of MRPL13, BCL2A1 and TP53AIP1 were compared between the breast cancer group and the control group. The mRNA expression levels of MRPL13, BCL2A1 and TP53AIP1 were compared between the responsive and non-responsive groups. The differences in immune function indicators before and after chemotherapy between the responsive and non-responsive groups, were compared. The correlations of the mRNA expression levels of MRPL13, BCL2A1 and TP53AIP1 with immune indicators were analyzed. Factors influencing chemotherapy efficacy were screened.
    Results The mRNA expression levels of MRPL13 and BCL2A1 in the breast cancer group were higher than those in the control group, while the mRNA expression level of TP53AIP1 was lower, with statistically significant differences (P < 0.05). In the responsive group, the mRNA expression levels of MRPL13 and BCL2A1 were lower than those in the non-responsive group, while the mRNA expression level of TP53AIP1 was higher, with statistically significant differences (P < 0.05). After chemotherapy, the IgM concentration in the responsive group was higher than that in the non-responsive group, with a statistically significant difference (P < 0.05). The proportion of CD8+ cells in the responsive group was lower than that in the non-responsive group, with a statistically significant difference (P < 0.05). The mRNA expression level of MRPL13 was positively correlated with IgM, IgG and CD8+ (r=0.672, 0.716, 0.824, P < 0.05). The mRNA expression level of BCL2A1 was positively correlated with IgA and CD4+ (r=0.654, 0.862, P < 0.05). The mRNA expression level of TP53AIP1 was negatively correlated with CD4+ and CD8+ (r=-0.846, -0.792, P < 0.05). High expressions of MRPL13 and BCL2A1 were independent risk factors for chemotherapy efficacy in breast cancer patients (P < 0.05), while high expression of TP53AIP1 was protective factor (P < 0.05).
    Conclusion The mRNA expression levels of MRPL13, BCL2A1 and TP53AIP1 in the serum of triple-negative breast cancer patients undergoing chemotherapy are correlated with the levels of IgM, IgG and IgA, the proportions of CD4+ and CD8+ T cells, and chemotherapy efficacy. High expression of MRPL13 and BCL2A1 are independent risk factors for poor chemotherapy efficacy, while high expression of TP53AIP1 is a protective factor.

     

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