Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Liaocheng People's Hospital, Liaocheng, Shandong, China.
Comput Math Methods Med. 2022 Oct 14;2022:7397250. doi: 10.1155/2022/7397250. eCollection 2022.
PDP1 has been reported in multiple diseases. However, it has not been fully explored in ovarian cancer (OC). The public data was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed gene analysis was conducted out using the limma package. Prognosis analysis was performed using the survival package. Gene Set Enrichment Analysis (GSEA) was performed using the fgsea package. Immune infiltration analysis was performed based on the CIBERSORT algorithm. CCK8 assay was used to evaluate the cell proliferation ability of cancer cells. Transwell assay was used for the invasion and migration ability. Our result showed that PDP1 was overexpressed in OC tissue in RNA and protein level based on multiple databases (TCGA, GSE18520, GSE27651, and GSE54388). At the same time, we found PDP1 was correlated with poor prognosis and worse clinical parameters. In vitro experiment showed that PDP1 could significantly promote proliferation, invasion, and migration ability of OC cells. GSEA analysis showed that in the OC patients with high PDP1 expression, the pathway of IL6/JAK/STAT3 signaling, interferon-alpha response, apoptosis, adipogenesis, KRAS signaling, and IL2/STAT5 signaling was activated, which might be responsible for its oncogenic effect in OC. Immune infiltration analysis indicated that PDP1 was positively correlated with activated myeloid dendritic cells, resting CD4 memory T cells, neutrophil, and M1 and M2 macrophages, yet negatively correlated with M0 macrophages, plasma B cells, T cells, and activated CD4 memory T cells. Drug sensitivity analysis showed a negative correlation between PDP1 expression and the IC50 of bleomycin and gemcitabine, yet a positive correlation of cisplatin, indicating that the OC patients with high PDP1 expression might be more sensitive to bleomycin and gemcitabine and more resistant to cisplatin. PDP1 could facilitate OC progression and is associated with patient prognosis and chemosensitivity, making it an underlying biomarker of OC.
PDP1 已在多种疾病中被报道。然而，在卵巢癌（OC）中尚未被充分研究。公共数据从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中下载。使用 limma 包进行差异表达基因分析。使用 survival 包进行预后分析。使用 fgsea 包进行基因集富集分析（GSEA）。基于 CIBERSORT 算法进行免疫浸润分析。使用 CCK8 测定法评估癌细胞的增殖能力。Transwell 测定法用于评估侵袭和迁移能力。我们的结果表明，基于多个数据库（TCGA、GSE18520、GSE27651 和 GSE54388），PDP1 在 OC 组织中在 RNA 和蛋白质水平上均过度表达。同时，我们发现 PDP1 与不良预后和更差的临床参数相关。体外实验表明，PDP1 可显著促进 OC 细胞的增殖、侵袭和迁移能力。GSEA 分析表明，在 PDP1 高表达的 OC 患者中，IL6/JAK/STAT3 信号通路、干扰素-α反应、细胞凋亡、脂肪生成、KRAS 信号通路和 IL2/STAT5 信号通路被激活，这可能是其在 OC 中的致癌作用的原因。免疫浸润分析表明，PDP1 与活化的髓样树突状细胞、静止的 CD4 记忆 T 细胞、中性粒细胞以及 M1 和 M2 巨噬细胞呈正相关，而与 M0 巨噬细胞、血浆 B 细胞、T 细胞和活化的 CD4 记忆 T 细胞呈负相关。药物敏感性分析表明，PDP1 表达与博来霉素和吉西他滨的 IC50 呈负相关，与顺铂呈正相关，这表明 PDP1 高表达的 OC 患者可能对博来霉素和吉西他滨更敏感，对顺铂更耐药。PDP1 可促进 OC 进展，并与患者预后和化疗敏感性相关，使其成为 OC 的潜在生物标志物。
