基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
一种预测乳腺癌新辅助化疗反应和预后的新型十二基因特征
英文原题：A novel twelve-gene signature to predict neoadjuvant chemotherapy response and prognosis in breast cancer.
查看英文原题
A novel twelve-gene signature to predict neoadjuvant chemotherapy response and prognosis in breast cancer.
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研究概要
一种新的 12 基因特征可用于预测乳腺癌 NAC 反应并预测预后。
研究思路结论见上方概要
背景
准确评估新辅助化疗（NAC）的疗效可为乳腺癌全身治疗提供重要信息，这涉及药物反应、预后并指导进一步治疗。基因图谱克服了经典病理评价标准检测指标相对有限和观察主观性的缺点，但操作复杂且费用高昂。因此，开发一种更准确、可重复且经济的的新辅助化疗疗效评估方法至关重要。
方法
我们分析了GSE25066数据集中化疗耐药乳腺癌细胞系和化疗耐药乳腺癌患者肿瘤的转录谱。我们初步筛选出常见的显著差异表达基因，并利用LASSO回归以及单因素和多因素分析构建了NAC反应风险模型。比较了高风险组和低风险组之间肿瘤细胞的生物信息学特征、免疫特征和预后的差异。通过CMap数据库筛选了可能逆转乳腺癌化疗耐药性的潜在药物。
结果
36个基因在NAC化疗耐药肿瘤和细胞中相较于敏感肿瘤和野生型细胞共同上调/下调。通过LASSO回归，我们获得了一个由12个基因组成的风险模型。该风险模型将患者分为高风险组和低风险组。单因素和多因素Cox回归分析表明，风险评分是评估乳腺癌NAC反应的独立预后因素。不同风险组的肿瘤在分子生物学特征、TIL（肿瘤浸润淋巴细胞）和免疫抑制分子表达方面表现出显著差异。我们的结果提示，该风险评分也是乳腺癌的一个良好预后因素。最后，我们筛选了可能逆转乳腺癌化疗耐药性的潜在药物。
展开英文摘要原文
BACKGROUND
Accurate evaluation of the response to neoadjuvant chemotherapy (NAC) provides important information about systemic therapies for breast cancer, which implies pharmacological response, prognosis, and guide further therapy. Gene profiles overcome the shortcomings of the relatively limited detection indicators of the classical pathological evaluation criteria and the subjectivity of observation, but are complicated and expensive. Therefore, it is essential to develop a more accurate, repeatable, and economical evaluation approach for neoadjuvant chemotherapy responses.
METHODS
We analyzed the transcriptional profiles of chemo-resistant breast cancer cell lines and tumors of chemo-resistant breast cancer patients in the GSE25066 dataset. We preliminarily screened out common significantly differentially expressed genes and constructed a NAC response risk model using LASSO regression and univariate and multivariate analyses. The differences in bioinformatic features of tumor cells, immune characteristics, and prognosis were compared between high and low-risk group. The potential drugs that could reverse chemotherapy resistance in breast cancer were screened by the CMap database.
RESULTS
Thirty-six genes were commonly up/down-regulated in both NAC chemo-resistant tumors and cells compared to the sensitive tumors and wild-type cells. Through LASSO regression, we obtained a risk model composed of 12 genes. The risk model divided patients into high and low-risk groups. Univariate and multivariate Cox regression analyses suggested that the risk score is an independent prognostic factor for evaluating NAC response in breast cancer. Tumors in risk groups exhibited significant differences in molecular biological characteristics, tumor-infiltrating lymphocytes, and immunosuppressive molecule expression. Our results suggested that the risk score was also a good prognostic factor for breast cancer. Finally, we screened potential drugs that could reverse chemotherapy resistance in breast cancer.
CONCLUSION
A novel 12 gene-signature could be used to predict NAC response and predict prognosis in breast cancer.
论文信息
- 作者
- Wu J、Tian Y、Liu W、Zheng H、Xi Y、Yan Y、Hu Y、Liao B
- 单位
- Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Frontiers in immunology2022
- 原文标识
- PubMed 36341435 · DOI 10.3389/fimmu.2022.1035667
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