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Integrative analysis deciphers the heterogeneity of cancer-associated fibroblast and implications on clinical outcomes in ovarian cancers
Computational and Structural Biotechnology Journal ( IF 6 ) Pub Date : 2022-11-14 , DOI: 10.1016/j.csbj.2022.11.025
Yan Zhao 1 , Song Mei 2 , Yixuan Huang 3 , Junru Chen 4 , Xinlei Zhang 3 , Peng Zhang 5, 6
Affiliation  

Accumulating evidence has recognized that cancer-associated fibroblasts (CAFs) are major players in the desmoplastic stroma of ovarian cancer, modulating tumor progression and therapeutic response. However, it is unclear regarding the signatures of CAFs could be utilized to predict the clinical outcomes of ovarian cancer patients. To fill in this gap, we explored the intratumoral compartment of ovarian cancer by analyzing the single-cell RNA-sequencing (scRNA-seq) datasets of ovarian carcinoma samples, and identified two distinct CAFs (tumor-promoting CAF_c1 subtype and myofibroblasts-like CAF_c2 subtype). The clinical significance of CAF subtypes was further validated in The Cancer Genomics Atlas (TCGA) database and other independent immunotherapy response datasets, and the results revealed that the patients with a higher expression of CAF_c1 signatures had a worse prognosis and showed a tendency of resistance to immunotherapy. This work uncovered the signatures of the CAF_c1 subtype that could serve as a novel prognostic indicator and predictive marker for immunotherapy.



中文翻译:

综合分析破译了癌症相关成纤维细胞的异质性及其对卵巢癌临床结果的影响

越来越多的证据表明,癌症相关成纤维细胞 (CAF) 是卵巢癌促纤维增生基质的主要参与者,可调节肿瘤进展和治疗反应。然而,尚不清楚 CAF 的特征是否可用于预测卵巢癌患者的临床结果。为了填补这一空白,我们通过分析卵巢癌样本的单细胞 RNA 测序 (scRNA-seq) 数据集探索了卵巢癌的瘤内区室,并确定了两种不同的 CAF(肿瘤促进 CAF_c1 亚型和肌成纤维细胞样 CAF_c2亚型)。CAF 亚型的临床意义在癌症基因组学图谱 (TCGA) 数据库和其他独立的免疫治疗反应数据集中得到进一步验证,结果显示,CAF_c1 signatures 表达较高的患者预后较差,并表现出对免疫治疗耐药的倾向。这项工作揭示了 CAF_c1 亚型的特征,可以作为免疫治疗的新型预后指标和预测标记。

更新日期:2022-11-17
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