Identification of lactate-related subgroups and prognostic model in triple-negative breast cancer
Identification of lactate-related subgroups and prognostic model in triple-negative breast cancer
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DOI：
10.1007/s00432-023-05171-6
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发表时间：
2023-07
影响因子：
3.6
通讯作者：
Shan Huang;Lin-Yu Wu;Y. Qiu;Yi Xie;Hao-xiang Wu;Ying-Qing Li;Xinhua Xie
中科院分区：
文献类型：
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作者：
Shan Huang;Lin-Yu Wu;Y. Qiu;Yi Xie;Hao-xiang Wu;Ying-Qing Li;Xinhua Xie
背景三阴性乳腺癌（TNBC）是一种高度侵袭性的乳腺癌亚型，表现出糖酵解能力升高。乳酸作为糖酵解的副产物，被认为是主要的肿瘤代谢物，在肿瘤发生和肿瘤微环境重塑中起重要作用。然而，乳酸盐在TNBC中的潜在作用尚未完全了解。在这项研究中，我们的目标是确定糖尿病相关的乳酸基因（PLGs），并构建一个乳酸相关的预后模型（LRPM）为TNBC.MethodsFirst，我们应用乳酸相关基因TNBC样本进行分类，使用分层聚类算法。然后，我们进行对数秩分析和最小绝对收缩和选择算子分析，以筛选PLG和构建LRPM。使用CCK 8测定法和克隆形成测定法研究所鉴定的PLG在TNBC中的生物学功能。最后，我们根据乳酸盐风险评分和肿瘤临床分期构建了诺模图。我们使用的操作特征曲线和决策曲线分析，以评估预测能力的nomogram.ResultsOur结果表明，TNBC样本可以分为两个亚组具有不同的生存概率。三个可以抑制TNBC细胞增殖的基因（NDUFAF3、CARS2和FH）被鉴定为PLG。此外，LRPM和诺模图表现出良好的预测性能TNBC患者projective.ConclusionWe已经开发出一种新的LRPM，使风险分层和识别不良分子亚型TNBC患者，在临床实践中表现出巨大的潜力。
BackgroundTriple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that exhibits elevated glycolytic capacity. Lactate, as a byproduct of glycolysis, is considered a major oncometabolite that plays an important role in oncogenesis and remodeling of the tumor microenvironment. However, the potential roles of lactate in TNBC are not yet fully understood. In this study, our goal was to identify prognosis-related lactate genes (PLGs) and construct a lactate-related prognostic model (LRPM) for TNBC.MethodsFirst, we applied lactate-related genes to classify TNBC samples using a hierarchical clustering algorithm. Then, we performed the log-rank analysis and the least absolute shrinkage and selection operator analysis to screen PLGs and construct the LRPM. The biological functions of the identified PLGs in TNBC were investigated using CCK8 assay and clone formation assay. Finally, we constructed a nomogram based on the lactate-risk score and tumor clinical stage. We used the operating characteristic curve and decision curve analysis to evaluate the predictive capability of the nomogram.ResultsOur results showed that the TNBC samples could be classified into two subgroups with different survival probabilities. Three genes (NDUFAF3, CARS2 and FH), which can suppress TNBC cell proliferation, were identified as PLGs. Moreover, the LRPM and nomogram exhibited excellent predictive performance for TNBC patient prognosis.ConclusionWe have developed a novel LRPM that enables risk stratification and identification of poor molecular subtypes in TNBC patients, showing great potential in clinical practice.