研究动态
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空间转录组学和 CT 表型的综合分析,揭示复发性和非复发性高级别浆液性卵巢癌的新分子特征。

Integrated analysis of spatial transcriptomics and CT phenotypes for unveiling the novel molecular characteristics of recurrent and non-recurrent high-grade serous ovarian cancer.

发表日期:2024 Aug 12
作者: Hye-Yeon Ju, Seo Yeon Youn, Jun Kang, Min Yeop Whang, Youn Jin Choi, Mi-Ryung Han
来源: Biomarker Research

摘要:

高级别浆液性卵巢癌(HGSOC)以其异质性、高复发率和转移性而闻名,通常在分散于多个部位后才被诊断出来,约80%的患者会出现复发。尽管对其转移性质有了更好的了解,HGSOC 患者的生存率仍然很低。我们的研究利用空间转录组学 (ST) 来解释肿瘤微环境,并利用计算机断层扫描 (CT) 来检查 8 名 HGSOC 患者的空间特征,分为复发性和复发性。 (R) 和难以收集的非复发 (NR) 组。通过将 ST 数据与公共单细胞 RNA 测序数据、批量 RNA 测序数据和 CT 数据相结合,我们确定了特定的细胞群富集和差异表达基因,与 CT 表型相关。重要的是,我们阐明了通过 NF-κB、氧化磷酸化、G2/M 检查点、E2F 靶点和 MYC 靶点的肿瘤坏死因子-α 信号传导可作为复发指标(不良预后标志物),并且这些途径在R 组和某些 CT 表型。此外,我们还发现了许多指示不复发的预后标志物(良好的预后标志物)。 PTGDS 表达下调与内部 HGSOC 样品和公共 HGSOC TCIA 和 TCGA 样品中较高数量的接种位点 (≥3) 有关。此外,根据我们的 ST 数据,在 R 组中观察到肿瘤和基质区域中的 PTGDS 表达低于 NR 组。在我们的 ST 和放射基因组学分析中,还发现趋化相关标记物(CXCL14 和 NTN4)以及与免疫调节相关的标记物(DAPL1 和 RNASE1)是良好的预后标记物。这项研究证明了结合 CT 和 ST 的放射基因组学在识别疾病方面的潜力。 HGSOC 的诊断和治疗目标,标志着迈向个性化医疗的一步。© 2024。作者。
High-grade serous ovarian cancer (HGSOC), which is known for its heterogeneity, high recurrence rate, and metastasis, is often diagnosed after being dispersed in several sites, with about 80% of patients experiencing recurrence. Despite a better understanding of its metastatic nature, the survival rates of patients with HGSOC remain poor.Our study utilized spatial transcriptomics (ST) to interpret the tumor microenvironment and computed tomography (CT) to examine spatial characteristics in eight patients with HGSOC divided into recurrent (R) and challenging-to-collect non-recurrent (NR) groups.By integrating ST data with public single-cell RNA sequencing data, bulk RNA sequencing data, and CT data, we identified specific cell population enrichments and differentially expressed genes that correlate with CT phenotypes. Importantly, we elucidated that tumor necrosis factor-α signaling via NF-κB, oxidative phosphorylation, G2/M checkpoint, E2F targets, and MYC targets served as an indicator of recurrence (poor prognostic markers), and these pathways were significantly enriched in both the R group and certain CT phenotypes. In addition, we identified numerous prognostic markers indicative of nonrecurrence (good prognostic markers). Downregulated expression of PTGDS was linked to a higher number of seeding sites (≥ 3) in both internal HGSOC samples and public HGSOC TCIA and TCGA samples. Additionally, lower PTGDS expression in the tumor and stromal regions was observed in the R group than in the NR group based on our ST data. Chemotaxis-related markers (CXCL14 and NTN4) and markers associated with immune modulation (DAPL1 and RNASE1) were also found to be good prognostic markers in our ST and radiogenomics analyses.This study demonstrates the potential of radiogenomics, combining CT and ST, for identifying diagnostic and therapeutic targets for HGSOC, marking a step towards personalized medicine.© 2024. The Author(s).