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细胞凋亡相关基因及其在预测新辅助乳腺癌治疗反应中的作用。

Apoptosis - associated genes and their role in predicting responses to neoadjuvant breast cancer treatment.

机构信息

Institute of Pathology, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

出版信息

Med Sci Monit. 2012 Jan;18(1):BR60-67. doi: 10.12659/msm.882205.

DOI:10.12659/msm.882205
PMID:22207111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3560664/
Abstract

BACKGROUND

Neoadjuvant chemotherapy is used in the treatment of breast carcinoma because it substantially reduces the size of the primary tumor and lymph node metastases. The present study investigated biomarkers that can predict a pathologic response to the therapy.

MATERIAL/METHODS: The role of apoptosis in regression of the tumors after neoadjuvant chemotherapy was determined by TUNEL and anti-active caspase 3 assay. The transcriptional profile of 84 key apoptosis genes was evaluated in both pre-therapeutically obtained tumor tissue by core needle biopsy and in specimens removed by final surgery, using a pathway-specific real-time PCR assay. Obtained data were analyzed by hierarchical cluster analysis and correlation analysis. The immunohistochemical profile of each tumor was determined using the standard ABC method.

RESULTS

On the basis of a hierarchical cluster analysis of 13 significantly changed genes, we divided patients into good and poor prognosis groups, which correlate well with progression-free survival. In the good prognosis group, we found a statistically significant down-regulation of the expression of MCL1 and IGF1R genes after neoadjuvant treatment. We also found a statistically significant overexpression of BCL2L10, BCL2AF1, CASP8, CASP10, CASP14, CIDEB, FADD, HRK, TNFRSF25, TNFSF8 and CD70 genes. In contrast, we found up-regulation of IGF1R after the treatment in the group with poor prognosis.

CONCLUSIONS

Gene expression profiling using real-time PCR assay is a valuable research tool for the investigation of molecular markers, which reflect tumor biology and treatment response.

摘要

背景

新辅助化疗被用于乳腺癌的治疗，因为它可以显著缩小原发肿瘤和淋巴结转移灶的大小。本研究旨在探索可以预测治疗病理反应的生物标志物。

材料/方法：通过 TUNEL 和抗活性 caspase 3 检测，确定了细胞凋亡在肿瘤经新辅助化疗后发生退缩中的作用。通过特定通路的实时 PCR 检测，评估了 84 个关键凋亡基因在术前核心针活检获得的肿瘤组织和最终手术切除标本中的转录谱。利用层次聚类分析和相关性分析对获得的数据进行分析。使用标准的 ABC 方法确定每个肿瘤的免疫组织化学特征。

结果

基于对 13 个显著变化基因的层次聚类分析，我们将患者分为预后良好和预后不良两组，与无进展生存期相关性良好。在预后良好组中，我们发现新辅助治疗后 MCL1 和 IGF1R 基因的表达明显下调。我们还发现 BCL2L10、BCL2AF1、CASP8、CASP10、CASP14、CIDEB、FADD、HRK、TNFRSF25、TNFSF8 和 CD70 基因的表达明显上调。相比之下，我们发现预后不良组中 IGF1R 基因在治疗后上调。

结论

使用实时 PCR 检测进行基因表达谱分析是研究反映肿瘤生物学和治疗反应的分子标志物的有价值的研究工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/33d3a292301f/medscimonit-18-1-BR60-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/33e40bcffe1a/medscimonit-18-1-BR60-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/ad3894fd29d2/medscimonit-18-1-BR60-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/a3dd69cee500/medscimonit-18-1-BR60-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/33d3a292301f/medscimonit-18-1-BR60-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/33e40bcffe1a/medscimonit-18-1-BR60-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/ad3894fd29d2/medscimonit-18-1-BR60-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/a3dd69cee500/medscimonit-18-1-BR60-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1313/3560664/33d3a292301f/medscimonit-18-1-BR60-g004.jpg

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