CELL INTELLIGENCE · 肿瘤细胞治疗研究

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与高级别浆液性卵巢癌转移和进展相关的候选因素特征分析

英文原题：Characterization of candidate factors associated with the metastasis and progression of high-grade serous ovarian cancer.

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Characterization of candidate factors associated with the metastasis and progression of high-grade serous ovarian cancer.

PubMed 2023/06/08（内容时间） Chin Med J (Engl) Q1 · IF 9.1（JCR 2025）

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技术：NK 细胞卵巢癌地区：中国
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研究概要

本研究通过整合生物信息学分析，描述了在 HGSOC 原发肿瘤和匹配转移肿瘤中筛选 DEGs 的过程。我们鉴定出六个与 HGSOC 进展相关的枢纽基因，尤其是 FAP 和 SFRP2，这可能为预测预后提供有效靶点，并为 HGSOC 的个体化治疗策略提供新见解。

研究思路结论见上方概要

背景

高级别浆液性卵巢癌（HGSOC）因其极强的转移特性，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子的特征。

方法

从美国国家生物技术信息中心（NCBI）基因表达综合数据库（GEO）中的三项独立研究中，获取了HGSOC患者原发肿瘤和配对的网膜转移肿瘤样本的转录组数据。利用癌症基因组图谱（TCGA）数据库中的数据，筛选差异表达基因（DEGs），以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）数据库评估枢纽基因的免疫景观。最后，使用25例HGSOC患者的癌组织和10例正常输卵管组织，进行免疫组织化学（IHC）染色，以量化与国际妇产科联盟（FIGO）分期相关的枢纽基因的表达水平。

结果

14个DEGs，ADIPOQ、ALPK2、BARX1、CD37、CNR2、COL5A3、FABP4、FAP、GPR68、ITGBL1、MOXD1、PODNL1、SFRP2和TRAF3IP3，在每个数据库的转移性肿瘤中均上调，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枢纽基因。所有枢纽基因均与肿瘤微环境浸润相关，尤其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盟（FIGO）分期呈正相关，并且通过IHC证实，与原发性肿瘤样本和正常组织相比，其在转移样本中的蛋白表达水平升高（分别为P = 0.0002和P = 0.0001）。

展开英文摘要原文
BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

论文信息

作者
Liu H、Zhou L、Cheng H、Wang S、Luan W、Cai E、Ye X、Zhu H
单位
Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.China
期刊
Chinese medical journal2023 Dec 20
原文标识
PubMed 37284741　·　DOI 10.1097/CM9.0000000000002328

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