Wang Zonghan, Dong Hao, Li Wei, Han Fujun, Zhao Lei
Department of the Oncology, Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin, China.
J Cancer. 2023 Apr 17;14(6):1049-1061. doi: 10.7150/jca.81430. eCollection 2023.
While peroxisome proliferator-activated receptor δ (PPAR-δ) and its associated signaling pathways have been shown to play an important regulatory role in various malignant tumors, in breast cancer, its potential influence on immune infiltration and its ability to serve as a prognostic marker remains unclear. BRCA patient samples with matched paracancerous samples were obtained from The Cancer Genome Atlas (TCGA). PPAR-δ expression, its potential effect on immune cell infiltration and its association to clinicopathological features were examined. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Single-Sample Gene Set Enrichment Analysis (ssGSEA) were utilized for functional and pathway enrichment and to quantify the extent of immune cell infiltration. Kaplan-Meier analysis and Cox regression analysis (nomogram) were performed to assess the association between PPAR- δ and predicted survival. To confirm these findings, an allograft tumor mouse model was generated and treated with a PPAR-δ inhibitor to examine the role of PPAR-δ expression ; while immunohistochemistry (IHC) was performed to examine PPAR-δ expression in paired BRCA patient samples . Overall, the findings presented herein suggest that PPAR-δ plays a crucial role in breast cancer progression and prognosis and may serve as a survival predictive biomarker.
虽然过氧化物酶体增殖物激活受体δ（PPAR-δ）及其相关信号通路已被证明在各种恶性肿瘤中发挥重要的调节作用，但在乳腺癌中，其对免疫浸润的潜在影响及其作为预后标志物的能力仍不清楚。从癌症基因组图谱（TCGA）获得了具有匹配癌旁样本的BRCA患者样本。检测了PPAR-δ表达、其对免疫细胞浸润的潜在影响及其与临床病理特征的关联。利用基因本体（GO）分析、京都基因与基因组百科全书（KEGG）、基因集富集分析（GSEA）和单样本基因集富集分析（ssGSEA）进行功能和通路富集，并量化免疫细胞浸润程度。进行Kaplan-Meier分析和Cox回归分析（列线图）以评估PPAR-δ与预测生存之间的关联。为了证实这些发现，构建了同种异体移植肿瘤小鼠模型并用PPAR-δ抑制剂进行处理，以研究PPAR-δ表达的作用；同时进行免疫组织化学（IHC）检测配对BRCA患者样本中的PPAR-δ表达。总体而言，本文提出的研究结果表明，PPAR-δ在乳腺癌进展和预后中起关键作用，可能作为生存预测生物标志物。
