Fan Lili, Lei Han, Lin Ying, Zhou Zhengwei, Shu Guang, Yan Zhipeng, Chen Haotian, Zhang Tianxiang, Yin Gang
Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China.
School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
Front Mol Biosci. 2021 Jul 30;8:670666. doi: 10.3389/fmolb.2021.670666. eCollection 2021.
Immune checkpoint blocking (ICB) immunotherapy has achieved great success in the treatment of various malignancies. Although not have been approved for the treatment of ovarian cancer (OC), it has been actively tested for the treatment of OC. However, biomarkers that could indicate the immune status of OC and predict the response to ICB are rare. We downloaded RNAseq and clinical data of OC from The Cancer Genome Atlas (TCGA). Data analysis revealed both TMB and immunity were significantly related to better survival of OC. Up-regulated differentially expressed genes (Up-DEGs) were identified by analyzing the gene expression levels. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the "GSVA" and "limma" package in R software. The correlation of genes with overall survival was also analyzed by conducted Kaplan-Meier survival analysis. Four genes, CXCL13, FCRLA, MS4A1, and PLA2G2D were found positively correlated with better prognosis of OC and mainly involved in immune response-related pathways. Finally, TIMER and TIDE were used to predict gene immune function and its association with immunotherapy. We found that these four genes were positively correlated with better response to immune checkpoint blockade-based immunotherapy. Altogether, CXCL13, FCRLA, MS4A1, and PLA2G2D may be used as potential therapeutic genes for reflecting OC immune status and predicting response to immunotherapy.
免疫检查点阻断(ICB)免疫疗法在各种恶性肿瘤的治疗中取得了巨大成功。尽管尚未被批准用于治疗卵巢癌(OC),但它已被积极用于OC治疗的试验。然而,能够指示OC免疫状态并预测对ICB反应的生物标志物却很少见。我们从癌症基因组图谱(TCGA)下载了OC的RNAseq和临床数据。数据分析显示,肿瘤突变负荷(TMB)和免疫均与OC更好的生存率显著相关。通过分析基因表达水平鉴定上调的差异表达基因(Up-DEGs)。在R软件的“GSVA”和“limma”包中进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。还通过进行Kaplan-Meier生存分析来分析基因与总生存期的相关性。发现CXCL13、FCRLA、MS4A1和PLA2G2D这四个基因与OC更好的预后呈正相关,并且主要参与免疫反应相关通路。最后,使用TIMER和TIDE来预测基因免疫功能及其与免疫治疗的关联。我们发现这四个基因与基于免疫检查点阻断的免疫治疗的更好反应呈正相关。总之,CXCL13、FCRLA、MS4A1和PLA2G2D可能用作反映OC免疫状态和预测免疫治疗反应的潜在治疗基因。