Xiao Lu, Li Jing, Liao Jiahao, Wu Min, Lu Xiujing, Li Jiehua, Zeng Yachang
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Oncol Rep. 2025 Jun;53(6). doi: 10.3892/or.2025.8897. Epub 2025 Apr 17.
Preeclampsia has been associated with a reduced risk of breast cancer (BC), but the mechanisms underlying this relationship remain unclear. It has been suggested that neutrophil extracellular traps (NETs), which are released upon neutrophil activation, play a key role in both preeclampsia and BC. To investigate this link, the single‑cell RNA sequencing dataset GSE173193 was analyzed and upregulated genes BCL2A1 and G0/G1 switch gene 2 (G0S2) were identified in neutrophils from preeclamptic placentas. These findings were validated using reverse transcription‑quantitative PCR and western blotting. Combined analyses of preeclampsia and BC tissues, from Gene Expression Omnibus (GSE24129) and The Cancer Genome Atlas databases respectively, identified 2,040 upregulated differentially expressed genes, including BCL2A1 and G0S2. Furthermore, these genes showed clinical relevance to BC, as demonstrated by Receiver Operating Characteristic curve, survival analyses and weighted gene co‑expression network analysis. Functional experiments revealed that overexpression of BCL2A1 and G0S2 increased NET release and inhibited BC cell proliferation, invasion and migration. The present study provides novel insights into the shared molecular pathways of preeclampsia and BC, emphasizing NETs as a potential protective mechanism as increased NET production in preeclampsia may contribute to a reduced BC risk by influencing tumor progression and offer avenues for further research into therapeutic interventions.
子痫前期与乳腺癌(BC)风险降低有关,但这种关系背后的机制尚不清楚。有人提出,中性粒细胞活化时释放的中性粒细胞胞外陷阱(NETs)在子痫前期和乳腺癌中都起关键作用。为了研究这种联系,分析了单细胞RNA测序数据集GSE173193,并在子痫前期胎盘的中性粒细胞中鉴定出上调基因BCL2A1和G0/G1转换基因2(G0S2)。这些发现通过逆转录定量PCR和蛋白质印迹法进行了验证。分别来自基因表达综合数据库(GSE24129)和癌症基因组图谱数据库的子痫前期和乳腺癌组织的联合分析,确定了2040个上调的差异表达基因,包括BCL2A1和G0S2。此外,这些基因显示出与乳腺癌的临床相关性,这通过受试者工作特征曲线、生存分析和加权基因共表达网络分析得到了证明。功能实验表明,BCL2A1和G0S2的过表达增加了NET的释放,并抑制了乳腺癌细胞的增殖、侵袭和迁移。本研究为子痫前期和乳腺癌的共同分子途径提供了新的见解,强调NETs作为一种潜在的保护机制,因为子痫前期中NET产生的增加可能通过影响肿瘤进展降低乳腺癌风险,并为进一步研究治疗干预提供了途径。