Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.
Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China.
Chin Med J (Engl). 2023 Dec 20;136(24):2974-2982. doi: 10.1097/CM9.0000000000002328. Epub 2023 Jun 8.
High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC.
Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages.
Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively).
This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
高级别浆液性卵巢癌（HGSOC）因其极高的转移性，是妇科癌症相关死亡的最大原因。本研究旨在探索和评估与 HGSOC 转移和进展相关的候选因素的特征。
从国家生物技术信息中心（NCBI）基因表达综合数据库（GEO）中三个独立的研究中获得 HGSOC 患者样本的转录组数据，这些样本来自原发肿瘤和匹配的大网膜转移肿瘤。使用癌症基因组图谱（TCGA）数据库的数据，选择差异表达基因（DEGs）来评估其对卵巢癌预后和进展的影响。通过肿瘤免疫估计资源（TIMER）数据库评估关键基因的免疫景观。最后，使用 25 例 HGSOC 患者的癌症组织和 10 例正常输卵管组织，通过免疫组织化学（IHC）定量分析与国际妇产科联合会（FIGO）分期相关的关键基因的表达水平。
在每个数据库中，14 个 DEGs（ADIPOQ、ALPK2、BARX1、CD37、CNR2、COL5A3、FABP4、FAP、GPR68、ITGBL1、MOXD1、PODNL1、SFRP2 和 TRAF3IP3）在转移肿瘤中上调，而 CADPS、GATA4、STAR 和 TSPAN8 下调。ALPK2、FAP、SFRP2、GATA4、STAR 和 TSPAN8 被选为与生存和复发显著相关的关键基因。所有关键基因都与肿瘤微环境浸润相关，特别是癌症相关成纤维细胞和自然杀伤（NK）细胞。此外，FAP 和 SFRP2 的表达与国际妇产科联合会（FIGO）分期呈正相关，通过免疫组织化学（IHC）证实它们在转移样本中的蛋白表达水平高于原发肿瘤样本和正常组织（P=0.0002 和 P=0.0001）。
本研究通过综合生物信息学分析描述了 HGSOC 原发肿瘤和匹配转移肿瘤中 DEGs 的筛选。我们鉴定了六个与 HGSOC 进展相关的关键基因，特别是 FAP 和 SFRP2，它们可能为预测预后提供有效的靶点，并为 HGSOC 的个体化治疗策略提供新的见解。
