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新辅助化疗后浸润性乳腺癌患者外周血淋巴细胞亚群、颗粒酶B和穿孔素的诊断效能及临床意义

Diagnostic Efficacy and Clinical Significance of Lymphocyte Subsets, Granzyme B and Perforin in the Peripheral Blood of Patients with Invasive Breast Cancer Following Neoadjuvant Chemotherapy.

作者信息

Liu Han, Zheng Ruinian, Zhuang Zhaowei, Xue Liwen, Chen Minggui, Wu Yuluo, Zeng Yan

机构信息

Precision Clinical Laboratory, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, Guangdong, People's Republic of China.

Phase I Clinical Trial Center, the Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, Guangdong, People's Republic of China.

出版信息

Cancer Manag Res. 2025 Mar 17;17:589-602. doi: 10.2147/CMAR.S502155. eCollection 2025.

Abstract

PURPOSE

Breast cancer, a predominant contributor to cancer-related mortality worldwide, is increasingly managed through the application of neoadjuvant chemotherapy (NAC). Analyzing the dynamic changes in peripheral blood lymphocyte subsets, granzyme B and perforin are crucial for investigating their roles in tumorigenesis, development and treatment; this study aimed to use these analyses to diagnose malignant breast tumor, assess the anti-tumor immunity and predict chemotherapy efficacy in breast cancer patients.

PATIENTS AND METHODS

To address this objective, a total of 582 peripheral blood samples were collected from healthy controls (n=47), benign breast disease patients (n=401) and breast cancer patients (n=134). Lymphocyte subsets, along with granzyme B and perforin expression, were assessed using flow cytometry. Changes before and after NAC were also monitored.

RESULTS

Breast cancer patients exhibited reduced proportions and absolute counts of CD3 and CD8 T cells, increased NK cell percentage and CD4/CD8 ratio, and higher levels of granzyme B and perforin in CD3, CD8 T cells and NK cells. Post-NAC, the percentages of CD3, CD4, CD8 T cells and NK cells increased, along with a higher CD4/CD8 ratio, while B cell percentages decreased compared to pre-NAC. Furthermore, the effective group showed higher percentages of CD3, CD8 T cells and lower percentages of B cells than the ineffective group post-NAC. Incidentally, Granzyme B and perforin expression in CD3 and CD8 T cells was elevated following postoperative chemotherapy.

CONCLUSION

These findings indicated that peripheral blood lymphocyte subsets, along with granzyme B and perforin levels, could serve as potential biomarkers for differentiating benign from malignant breast tumors, assessing anti-tumor immunity and predicting chemotherapy efficacy.

摘要

目的

乳腺癌是全球癌症相关死亡的主要原因,新辅助化疗(NAC)在其治疗中的应用日益广泛。分析外周血淋巴细胞亚群、颗粒酶B和穿孔素的动态变化对于研究它们在肿瘤发生、发展和治疗中的作用至关重要;本研究旨在通过这些分析来诊断乳腺恶性肿瘤、评估抗肿瘤免疫力并预测乳腺癌患者的化疗疗效。

患者与方法

为实现这一目标,共收集了582份外周血样本,来自健康对照者(n = 47)、乳腺良性疾病患者(n = 401)和乳腺癌患者(n = 134)。使用流式细胞术评估淋巴细胞亚群以及颗粒酶B和穿孔素的表达。同时监测NAC前后的变化。

结果

乳腺癌患者的CD3和CD8 T细胞比例及绝对计数降低,NK细胞百分比和CD4/CD8比值升高,CD3、CD8 T细胞和NK细胞中的颗粒酶B和穿孔素水平更高。NAC后,CD3、CD4、CD8 T细胞和NK细胞的百分比增加,CD4/CD8比值更高,而B细胞百分比与NAC前相比降低。此外,有效组在NAC后CD3、CD8 T细胞的百分比高于无效组,B细胞百分比低于无效组。顺便提及,术后化疗后CD3和CD8 T细胞中颗粒酶B和穿孔素的表达升高。

结论

这些发现表明,外周血淋巴细胞亚群以及颗粒酶B和穿孔素水平可作为区分乳腺良性和恶性肿瘤、评估抗肿瘤免疫力及预测化疗疗效的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6727/11928756/81c7a6e75244/CMAR-17-589-g0001.jpg

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