Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Ann N Y Acad Sci. 2022 Jun;1512(1):154-173. doi: 10.1111/nyas.14748. Epub 2022 Mar 5.
A major cause of gynecological cancer -related deaths worldwide, ovarian cancer is characterized by heterogeneity in both tumor cells and the tumor microenvironment (TME). Our study aimed to characterize tumor cell heterogeneity and the infiltration of M2 tumor-associated macrophages (TAMs) in the ovarian cancer TME by single-cell RNA-Seq (scRNA-Seq) analysis combined with bulk RNA sequencing (bulk RNA-Seq). Several highly variable genes were identified in ovarian cancer tissues, and tumor cell heterogeneity and infiltrating immune tumor cell heterogeneity were characterized in ovarian cancer cells. M2 TAMs in the TME were the predominant phenotype of TAM. Further, M2 TAM infiltration in the TME was negatively correlated with poor prognosis of ovarian cancer patients. Four M2 TAM-associated genes (SLAMF7, GNAS, TBX2-AS1, and LYPD6) correlated with the prognostic survival of ovarian cancer patients. Knockdown of SLAMF7 or GNAS mRNA repressed malignancy and cisplatin resistance of ovarian cancer cells. ScRNA-Seq combined with bulk RNA-Seq identified the same four genes associated with M2 TAMs. The prognostic risk score model based on these four genes may hold favorable predictive value for the prognosis of ovarian cancer patients.
一种主要的妇科癌症死亡原因——卵巢癌，其特征是肿瘤细胞和肿瘤微环境（TME）的异质性。我们的研究旨在通过单细胞 RNA 测序（scRNA-Seq）分析联合批量 RNA 测序（bulk RNA-Seq）来描述卵巢癌 TME 中的肿瘤细胞异质性和 M2 肿瘤相关巨噬细胞（TAMs）的浸润情况。我们在卵巢癌组织中鉴定了几个高度可变的基因，并描述了卵巢癌细胞的肿瘤细胞异质性和浸润免疫肿瘤细胞异质性。TME 中的 M2 TAMs 是 TAM 的主要表型。此外，TME 中 M2 TAM 的浸润与卵巢癌患者的不良预后呈负相关。四个与 M2 TAM 相关的基因（SLAMF7、GNAS、TBX2-AS1 和 LYPD6）与卵巢癌患者的预后生存相关。SLAMF7 或 GNAS mRNA 的敲低抑制了卵巢癌细胞的恶性和顺铂耐药性。scRNA-Seq 联合批量 RNA-Seq 鉴定出与 M2 TAMs 相关的相同四个基因。基于这四个基因的预后风险评分模型可能对卵巢癌患者的预后具有良好的预测价值。
