Department of Gynecologic Oncology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Dis Markers. 2022 Sep 26;2022:5940049. doi: 10.1155/2022/5940049. eCollection 2022.
The initiation and progression of cancer depend on the genetic alterations inherent in cancer cells, coupled with the mutual interplay of cancer cells with the surrounding tumor stroma. The platelet-derived growth factor (PDGF) family, as a mesenchymal growth factor, was involved in tumor progression by affecting the surrounding tumor stroma in some cancer types. However, the association of the PDGF family with the ovarian cancer stroma remains elusive. In our study, we first explored the expression pattern of the PDGF family using RNA expression profiles from public databases. We found that the PDGF family was highly expressed in tumor stroma compared with the corresponding epithelial components of ovarian cancer. In particular, PDGF receptors were weakly expressed in ovarian cancer tissues compared with the respective normal tissues; even in tumor mass, PDGF receptors were predominantly expressed by tumor stroma rather than ovarian cancer cells. Importantly, functional enrichment analyses and correlation analyses revealed that the PDGF family was strongly associated with activated stromal scores in ovarian cancer, including higher stromal scores, enriched pathways related to the extracellular matrix (ECM) organization and remodeling, elevated cancer-associated fibroblasts (CAFs) infiltration, and increased tumor-associated macrophages (TAMs) infiltration, especially macrophage M2. Besides, the positive correlations of the PDGF family with CAFs infiltration and macrophage M2 infiltration were observed in other various cancer types. Of note, the PDGF family was also involved in tumor progression-related pathways, such as transforming growth factor (TGF-) signaling, epithelial-mesenchymal transition (EMT), angiogenesis, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling. Higher expressions of PDGF receptors were also observed in ovarian cancer patients with venous or lymphatic invasion. Furthermore, we uncovered the prognostic prediction of the PDGF family in ovarian cancer and constructed a PDGF family-based risk prognosis model with a hazard ratio of 1.932 (95%confidence interval (CI) = 1.27-2.95) and value < 0.01 (AUC = 0.782, 0.752 for 1 year and 2 years, respectively). Taken together, we demonstrated that ovarian cancers with high PDGF family expression biologically exhibit malignant progression behaviors as well as poor clinical survival, which is attributed to the activated tumor stroma in ovarian cancer.
癌症的发生和发展取决于癌细胞固有的遗传改变，加上癌细胞与周围肿瘤基质的相互作用。血小板衍生生长因子 (PDGF) 家族作为一种间质生长因子，通过影响某些癌症类型的周围肿瘤基质，参与肿瘤的进展。然而，PDGF 家族与卵巢癌基质的关联仍然难以捉摸。在我们的研究中，我们首先使用公共数据库中的 RNA 表达谱探索了 PDGF 家族的表达模式。我们发现 PDGF 家族在肿瘤基质中的表达水平明显高于卵巢癌的相应上皮成分。特别是，PDGF 受体在卵巢癌组织中的表达水平明显低于相应的正常组织；即使在肿瘤组织中，PDGF 受体也主要由肿瘤基质而不是卵巢癌细胞表达。重要的是，功能富集分析和相关性分析表明，PDGF 家族与卵巢癌中激活的基质评分密切相关，包括更高的基质评分、富含细胞外基质 (ECM) 组织和重塑相关的途径、升高的癌相关成纤维细胞 (CAF) 浸润以及增加的肿瘤相关巨噬细胞 (TAM) 浸润，特别是巨噬细胞 M2。此外，在其他各种癌症类型中也观察到 PDGF 家族与 CAF 浸润和巨噬细胞 M2 浸润的正相关。值得注意的是，PDGF 家族还参与了肿瘤进展相关途径，如转化生长因子 (TGF-) 信号、上皮-间质转化 (EMT)、血管生成和磷脂酰肌醇 3-激酶-Akt (PI3K-Akt) 信号。在有静脉或淋巴浸润的卵巢癌患者中，PDGF 受体的表达也更高。此外，我们揭示了 PDGF 家族在卵巢癌中的预后预测，并构建了一个基于 PDGF 家族的风险预后模型，其危险比为 1.932（95%置信区间 (CI) = 1.27-2.95）， 值<0.01（AUC = 0.782，0.752 分别用于 1 年和 2 年）。总之，我们证明了 PDGF 家族高表达的卵巢癌在生物学上表现出恶性进展行为和不良的临床生存，这归因于卵巢癌中激活的肿瘤基质。
