转录组分析鉴定三阴性乳腺癌中乳酸化相关基因及预后模型的建立

doi:10.19586/j.2095-2341.2025.0121

生物技术进展 ›› 2026, Vol. 16 ›› Issue (1): 196-204.DOI: 10.19586/j.2095-2341.2025.0121

转录组分析鉴定三阴性乳腺癌中乳酸化相关基因及预后模型的建立

张海月¹(), 郭文捷², 翟晓艺¹, 孙莉莉¹, 刁钟琪¹, 郭文佳¹^,³()

^1.新疆医科大学附属肿瘤医院肿瘤研究所，乌鲁木齐 830011
^2.新疆大学电气工程学院，乌鲁木齐 830046
^3.新疆医科大学附属肿瘤医院，新疆医工创新研究与生物医药转化重点实验室，乌鲁木齐 830011

收稿日期:2025-09-15 接受日期:2025-11-20 出版日期:2026-01-25 发布日期:2026-02-12
通讯作者: 郭文佳
作者简介:张海月 E-mail: 3220548635@qq.com；
基金资助:
新疆维吾尔自治区重点研发专项(2022B03019-4);新疆医科大学科研创新团队项目(XYD2024C09)

Transcriptional Group Analysis Identifies Lactylation-related Genes in Triple-negative Breast Cancer and Establishes a Prognostic Model

Haiyue ZHANG¹(), Wenjie GUO², Xiaoyi ZHAI¹, Lili SUN¹, Zhongqi DIAO¹, Wenjia GUO¹^,³()

^1.Departments of Cancer Research Institute，Affiliated Cancer Hospital of Xinjiang Medical University，Urumqi 830011，China
^2.School of Electrical Engineering，Xinjiang University，Urumqi 830046，China
^3.Xinjiang Key Laboratory of Medical-Engineering Innovation Research and Biomedical Translation，Affiliated Cancer Hospital of Xinjiang Medical University，Urumqi 830011，China

Received:2025-09-15 Accepted:2025-11-20 Online:2026-01-25 Published:2026-02-12
Contact: Wenjia GUO

摘要/Abstract

摘要：

三阴性乳腺癌具有代谢重编程特征，糖酵解途径的异常激活是其关键特征之一。乳酸作为糖酵解途径的终产物，可在细胞、器官及组织间发挥信号传导功能，从而促进肿瘤的侵袭与转移。近期研究首次揭示乳酸可作为底物参与新型翻译后修饰乳酸化。因此，围绕乳酸化相关基因在三阴性乳腺癌中的作用展开探讨。利用癌症基因组图谱（The Cancer Genome Atlas，TCGA）下载151例三阴性乳腺癌样本和113例癌旁样本的转录组数据及其相应的临床信息。通过差异分析、通路富集、单因素和多因素Cox分析得到乳酸化预后基因。在TCGA-TNBC训练队列中构建乳酸化相关基因的预后模型，GSE21653、GSE58812和METABRIC-TNBC作为验证队列进行模型验证。根据乳酸化风险评分将样本分为高乳酸化风险组和低乳酸化风险组，生存分析、受试工作者曲线和列线图进一步验证模型性能，并进一步分析该模型与免疫细胞浸润及药物敏感性的关联。结果显示，基于4个乳酸化相关基因建立的预后模型，对三阴性乳腺癌患者具有良好的预后预测能力。生存分析结果表明，高乳酸化风险评分与患者不良预后显著相关，高风险组患者的总体生存率均低于低风险组。同时，高低乳酸化风险组的患者在肿瘤免疫微环境浸润特征及药物反应敏感性方面均表现出显著差异。这一发现提示，乳酸化相关基因有望成为三阴性乳腺癌的新型分子生物标志物及潜在治疗靶点。

Abstract:

Triple-negative breast cancer exhibits metabolic reprogramming characteristics， with abnormal activation of the glycolytic pathway being one of its key features. As the end product of glycolysis， lactate functions as a signaling molecule between cells， organs， and tissues， thereby promoting tumor invasion and metastasis. Recent studies have revealed a novel biological function of lactate： it serves as a substrate for a novel post-translational modification termed "lactylation". Consequently， this study explored the role of lactylation-related genes in triple-negative breast cancer. Transcriptome data and corresponding clinical information from 151 triple-negative breast cancer samples and 113 adjacent normal samples were downloaded from The Cancer Genome Atlas （TCGA）. Differential analysis， pathway enrichment， univariate， and multivariate Cox analyses identified lactylation-associated prognostic genes. A prognostic model incorporating lactylation-related genes was constructed using the TCGA-TNBC training cohort and validation was performed using the GSE21653， GSE58812， and METABRIC-TNBC cohorts. Samples were stratified into high- and low-lactylation risk groups based on lactylation risk scores. Survival analysis， receiver operating characteristic curves， and scatter plots further validated model performance， with additional analysis exploring associations between the model and immune cell infiltration/drug sensitivity. The results showed that a prognostic model based on four lactylation-related genes has good predictive ability for triple-negative breast cancer patients. At the same time， patients in the high- and low-lactylation risk groups exhibited significant differences in tumor immune microenvironment infiltration characteristics and drug response sensitivity. This finding suggests that lactylation-related genes may have potential as novel molecular biomarkers and therapeutic targets for triple-negative breast cancer.

Key words: triple-nagetive breast cancer, lactylation-related genes, immune infiltration, drug sensitivity, prognosis model

中图分类号:

Q987.1

张海月, 郭文捷, 翟晓艺, 孙莉莉, 刁钟琪, 郭文佳. 转录组分析鉴定三阴性乳腺癌中乳酸化相关基因及预后模型的建立[J]. 生物技术进展, 2026, 16(1): 196-204.

Haiyue ZHANG, Wenjie GUO, Xiaoyi ZHAI, Lili SUN, Zhongqi DIAO, Wenjia GUO. Transcriptional Group Analysis Identifies Lactylation-related Genes in Triple-negative Breast Cancer and Establishes a Prognostic Model[J]. Current Biotechnology, 2026, 16(1): 196-204.

图/表 4

图1 鉴定三阴性乳腺癌中的乳酸化相关基因A：主成分分析；B：差异分析；C：层次聚类热图；D：富集分析；E：乳酸化基因筛选流程；F：差异基因和LRGs韦恩图；G：单因素Cox分析；H：多因素cox分析；I：预后基因差异表达箱线图；J：预后相关基因生存曲线；**、***分别表示差异在P<0.01、P<0.001水平上具有统计学意义

Fig. 1 Identification of genes associated with lactylation in triple-negative breast cancer

图2 构建乳酸化相关基因预后模型A~D：风险因子图；E~H：生存曲线；I~L：风险评分ROC曲线；M：列线图；N：多因素Cox分析；O：校准曲线；*、***表示差异在P<0.05、P<0.001水平上具有统计学意义

Fig. 2 Construction of a prognostic model for lactylation

图3 三阴性乳腺癌免疫浸润分析A：基质评分、免疫评分、Estimate评分；B：Xcell免疫分析；C：ssGSEA免疫浸润分析；D：CIBERSORT免疫浸润分析；N：高低风险组差异免疫检查；F：预后相关基因与免疫细胞相关性；*、**、***分别表示差异在P<0.05、P<0.01、P<0.001水平上具有统计学意义；ns表示无统计学意义

Fig. 3 Immune infiltration analysis in TNBC

图4 乳酸化相关基因预后模型预测药物敏感性注：ns表示无统计学意义；*、**、***表示在P<0.05、P<0.01、P<0.001水平上有统计学意义。

Fig. 4 LRGs prognostic model for predicting drug sensitivity

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转录组分析鉴定三阴性乳腺癌中乳酸化相关基因及预后模型的建立

Transcriptional Group Analysis Identifies Lactylation-related Genes in Triple-negative Breast Cancer and Establishes a Prognostic Model

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