Identification and validation of tumor microenvironment-related prognostic biomarkers in breast cancer.
Identification and validation of tumor microenvironment-related prognostic biomarkers in breast cancer.
复制标题
乳腺癌肿瘤微环境相关预后生物标志物的鉴定和验证
DOI：
10.21037/tcr-21-1248
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发表时间：
2021-10
影响因子：
0.9
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Zhong S;Jia Z;Zhang H;Gong Z;Feng J;Xu H
肿瘤微环境（TME）中的基质细胞和免疫细胞在肿瘤的诊断和预后中具有重要价值。我们的目标是确定预测乳腺癌TME生存的关键生物标志物。进行细胞类型富集分析以使用xCell方法用来自公共数据库的基因表达数据估计细胞评分。使用最小绝对收缩和选择算子（LASSO）回归来从细胞评分识别关键特征。在1,078例乳腺癌组织和112例癌旁正常组织中，TME中共有50个细胞得分不同。我们确定了预测乳腺癌存活的4细胞特征，包括肌细胞、自然杀伤T细胞（NKT）、常规树突状细胞（cDC）和皮脂腺细胞，其在测试集中得到验证。进一步分析表明，cDC评分是预测乳腺癌预后的关键标志。cDC评分与乳腺癌分子分型、分期及Ki 67表达水平显著相关。斯皮尔曼相关分析发现，cDC评分与HER 2表达水平呈负相关。高cDC评分可能预示更好的病理完全缓解率。机制分析表明，cDC评分高与免疫活性升高相关; IL-2是cDC评分高的关键基因; IL-2高表达的乳腺癌患者生存期较长。总之，cDC评分是预测乳腺癌预后的关键特征。cDC可以通过上调IL-2发挥抗肿瘤作用。
Stromal cells and immune cells in tumor microenvironment (TME) have been reported to have significant value in the diagnosis and prognosis of cancers. We aimed to identify key biomarkers predicting survival in the TME of breast cancer. Cell type enrichment analysis was performed to estimate cell scores using the xCell method with gene expression data from public database. Least absolute shrinkage and selection operator (LASSO) regression was used to identify key signature from the cell scores. Totally, 50 cells in TME had different scores between 1,078 breast cancer tissues and 112 adjacent normal tissues. We identified a 4-cell signature predicting breast cancer survival, including myocytes, natural killer T cell (NKT), conventional dendritic cell (cDC) and sebocytes, which was validated in the test set. Further analysis showed that cDC score was a key signature predicting prognosis of breast cancer. cDC score was significantly associated with molecular classification and stage of breast cancer, as well as expression level of Ki67. Spearman’s correlation analysis found that cDC score was inversely correlated with the expression level of HER2. High cDC score may predicate better pathological complete response rate. Mechanism analysis indicated high cDC score was associated with elevated immune activity; IL-2 was a key gene associated with high cDC score; and Breast cancer patients with high IL-2 expression had a longer survival time. In conclusion, cDC score was a key signature predicting prognosis for breast cancer. cDCs may exert antitumor effects by upregulating IL-2.
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影响因子：
5.6
作者：
Wang, Jinyan;Zhang, Qian;Feng, Jifeng
通讯作者：
Feng, Jifeng
DOI：
10.18632/aging.101415
发表时间：
2018-04-16
期刊：
Aging
影响因子：
--
作者：
Jia D;Li S;Li D;Xue H;Yang D;Liu Y
通讯作者：
Liu Y
影响因子：
64.5
作者：
Binnewies, Mikhail;Mujal, Adriana M.;Krummel, Matthew F.
通讯作者：
Krummel, Matthew F.
影响因子：
5.2
作者：
Oshi M;Newman S;Tokumaru Y;Yan L;Matsuyama R;Kalinski P;Endo I;Takabe K
通讯作者：
Takabe K
影响因子：
4.5
作者：
Penault-Llorca, Frederique;Radosevic-Robin, Nina
通讯作者：
Radosevic-Robin, Nina