单细胞转录组揭示PCLAF与ERO1A在乳腺癌进展中的作用及预后价值

doi:10.11904/j.issn.1002-3070.2025.05.009

摘要/Abstract

摘要： 目的基于单细胞转录组技术,系统解析乳腺癌由原发灶向淋巴结转移的分子特征,筛选可用于评估乳腺癌淋巴结转移风险及预测预后的潜在生物标志物。方法利用GEO乳腺癌单细胞数据集(GSE161529),整合正常乳腺组织、原发灶及配对淋巴结转移样本,构建单细胞转录组图谱;通过拷贝数变异(copy number variation,CNV)分析、并结合细胞轨迹分析、功能富集及差异表达分析,筛选与肿瘤进展密切相关的上皮细胞亚群及关键基因;并基于TCGA乳腺癌队列进行生存分析,验证关键基因的临床预后价值。结果共获得86 825个高质量细胞,并鉴定出7种主要细胞类型。原发灶与转移淋巴结中上皮细胞均具有恶性特征,存在NT→PT和NT→PT→MLN两条分化路径。进一步将上皮细胞划分为8个亚群(C1~C8),其中C4亚群主要与肿瘤增殖相关,C8亚群与肿瘤转移密切相关。核心基因PCLAF和ERO1A的高表达与患者不良预后显著相关(P＜0.001)。结论本研究揭示了乳腺癌从原发到转移的细胞分化谱系,并确定PCLAF与ERO1A为驱动乳腺癌进展的关键基因,可作为预测乳腺癌淋巴结转移及评估患者预后的潜在生物标志物。

关键词: 单细胞转录组测序, 乳腺癌, 增殖细胞核抗原钳夹相关因子, 内质网氧化还原酶1α, 预后

Abstract: Objective The aim of this study was to systematically analyze the molecular characteristics of breast cancer metastasis from the primary focus to lymph node based on single-cell transcriptomic technology,and screen potential biomarkers that could be used to assess the risk of lymph node metastasis of breast cancer and predict survival prognosis. Methods A single-cell RNA sequencing dataset of breast cancer(GSE161529)was integrated to construct a single-cell transcriptomic map by normal breast tissues,primary lesion and paired lymph node metastasis samples.Through CNV analysis,and combining cell trajectory analysis,functional enrichment,and differential expression analyses,epithelial cell subsets and key genes closely related to tumor progression were screened,and survival analysis was conducted based on the TCGA breast cancer cohort to verify the clinical prognostic value of key genes. Results A total of 86,825 high-quality cells were obtained,and 7 main cell types were identified.The epithelial cells in both the primary lesion and metastatic lymph nodes had malignant characteristics,and there were two main differentiation pathways:NT→PT and NT→PT→MLN.Epithelial cells were further divided into 8 subclusters(C1-C8).Among them,the C4 subgroup was mainly associated with tumor proliferation,whereas the C8 subgroup was closely related to metastasis.The high expression of core genes PCLAF and ERO1A was significantly correlated with poor prognosis in patients(P＜0.001). Conclusion This study reveals the cellular differentiation lineage of breast cancer from primary to metastasis,and identifies PCLAF and ERO1A as key genes driving the progress of breast cancer,which can be used as potential biomarkers to predict lymph node metastasis of breast cancer and evaluate the prognosis of patients.

Key words: single cell transcriptome sequencing, breast cancer, proliferating cell nuclear antigen clamp-associated factor, endoplasmic reticulum oxidoreductase 1 alpha, prognosis

中图分类号:

R737.9

李旭东, 刘通. 单细胞转录组揭示PCLAF与ERO1A在乳腺癌进展中的作用及预后价值[J]. 实用肿瘤学杂志, 2025, 39(5): 418-427.

LI Xudong, LIU Tong. The single cell transcriptome sequencing reveals the role and prognostic value of PCLAF and ERO1A in the progression of breast cancer[J]. Journal of Practical Oncology, 2025, 39(5): 418-427.

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