研究动态
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浸润高级别卵巢浆液性癌的Th2细胞:一种可以解释预后不良的特征。

Th2 cells infiltrating high-grade serous ovarian cancer: a feature that may account for the poor prognosis.

发表日期:2023 Mar 23
作者: Hao Su, Yueqi Jin, Changyu Tao, Hua Yang, Ence Yang, Wei-Guang Zhang, Fengzhi Feng
来源: Journal of Gynecologic Oncology

摘要:

我们旨在研究两组不同预后的高级别浆液性卵巢癌(HGSOC)患者的转录组谱差异,并鉴定可能的复发生物标记。对两组具有相似人口统计学特征但表现出进展自由生存期(PFS)不同的HGSOC患者进行了RNA测序。对恶性反应(PR;PFS≤6个月)和良性反应(GR;PFS≥12个月)组的转录组数据进行了比较。使用xCell评估肿瘤微环境中63个细胞的丰度。复发相关肿瘤浸润细胞的预测价值在基因表达纲目(GEO)和癌症基因组图谱(TCGA)数据集的队列数据中得到了验证。进行加权相关网络分析以确定与细胞浸润相关的基因。与GR患者相比,PR患者呈现出明显的肿瘤浸润免疫细胞相关的转录谱,例如较低的白细胞分化、激活和趋化因子特征。T辅助2(Th2)细胞浸润比例在PR组中明显高于GR组。Th2高浸润在GEO队列(6个月复发下曲线下面积=0.84)和TCGA队列(p=0.008)中与不利的预后显著相关。与Th2浸润相关的基因富集到细胞外基质组织和整合素结合末梢。PFS较短的HGSOC患者呈现出与肿瘤浸润免疫细胞相关的明显基因特征。Th2浸润水平可促进患者复发风险分层,并可能成为预后预测和免疫相关治疗的有前途的生物标记。©2023. 亚洲妇科肿瘤学会、韩国妇科肿瘤学会和日本妇科肿瘤学会。
We aimed to investigate the differences of transcriptome profile between 2 groups of high-grade serous ovarian cancer (HGSOC) patients with distinct outcomes and identify potential biomarkers for recurrence.RNA sequencing was performed in 2 groups of HGSOC patients with similar demographic characteristics but exhibiting distinct progression-free survival (PFS). Transcriptome data of poor response (PR; PFS ≤6 months) and good response (GR; PFS ≥12 months) group were compared. We employed xCell to evaluate the abundance of 63 cells in tumor microenvironment. The predictive value of recurrence-related tumor infiltration cells was validated in cohort data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) dataset. The weighted correlation network analysis was performed to identify the genes related to cell infiltration.PR patients exhibited a distinct tumor infiltration immune cells-related transcriptional profile compared to GR patients, such as lower signatures of leukocyte differentiation, activation and chemotaxis. The fraction of T-helper 2 (Th2) cells infiltration was significantly higher in PR group than in GR group. High infiltration of Th2 was significantly associated with unfavorable prognosis in the GEO cohort (area under the curve=0.84 at 6 months recurrence) and TCGA cohort (p=0.008). Genes enriched to extracellular matrix organization and integrin binding were relevant to Th2 infiltration.Patients with HGSOC having shorter PFS exhibited a distinct gene signature that related to tumor-infiltrating immune cells. The level of Th2 infiltration could facilitate patient recurrence risk stratification and may be a promising biomarker for prognosis prediction and immune-related treatment.© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.