Shi Xiaoxi, Liu Yuanlin, Cheng Shuai, Hu Haidi, Zhang Jian, Wei Minjie, Zhao Lin, Xin Shijie
Department of Vascular and Thyroid Surgery, The First Hospital, China Medical University, Shenyang, China.
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.
Front Oncol. 2021 Jul 21;11:651622. doi: 10.3389/fonc.2021.651622. eCollection 2021.
Cancer stem cells (CSCs) have been proven to influence drug resistance, recurrence, and metastasis in tumors. Our study aimed to identify stemness-related prognostic biomarkers for new therapeutic strategies in adrenocortical carcinoma.
RNA-seq data and clinical characteristics were downloaded from The Cancer Genome Atlas (TCGA). The stemness indexes, mDNAsi and mRNAsi, were calculated to classify all samples into low-score and high-score groups. Two algorithms, based on the R language, ESTIMATE and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to assess the immune cell infiltration states of adrenocortical carcinoma patients. Weighted Gene Co-expression Network Analysis (WGCNA) was used to find genes that were related to the stemness of cancer. By bioinformatics methods, the correlations between biomarkers capable of predicting immune checkpoint inhibitors (ICIs) responses and stemness of cancer were explored.
High-mRNAsi predicted shorter overall survival (OS) and a higher metastatic trend in adrenocortical carcinoma (ACC) patients. Compared with the low-mRNAsi group, the high-mRNAsi group had a lower ImmuneScore and StromalScroe. Twenty-two stemness-related prognostic genes were obtained by WGCNA, which focused on the function of the cell cycle and cell mitosis. Immune cell infiltration, especially CD8+T cell, increased in the low-mRNAsi group compared with the high-mRNAsi group. Lower expression of PD-L1, CTLA-4, and TIGHT was evaluated in the high-mRNAsi group.
ACC patients with high-mRNAsi have poor prognosis and less immune cell infiltration. Combined with the finding of lower expression of CTLA-4, TIGHT, and PD-L1 in the high-mRNAsi group, we came to the conclusion that stemness index is a potential biomarker to predict the effectiveness of ICIs.
癌症干细胞（CSCs）已被证明会影响肿瘤的耐药性、复发和转移。我们的研究旨在识别与干性相关的预后生物标志物，以用于肾上腺皮质癌的新治疗策略。
从癌症基因组图谱（TCGA）下载RNA测序数据和临床特征。计算干性指数mDNAsi和mRNAsi，将所有样本分为低分和高分两组。使用基于R语言的两种算法，即ESTIMATE和单样本基因集富集分析（ssGSEA）来评估肾上腺皮质癌患者的免疫细胞浸润状态。加权基因共表达网络分析（WGCNA）用于寻找与癌症干性相关的基因。通过生物信息学方法，探索能够预测免疫检查点抑制剂（ICIs）反应的生物标志物与癌症干性之间的相关性。
高mRNAsi预示肾上腺皮质癌（ACC）患者的总生存期（OS）较短且转移趋势较高。与低mRNAsi组相比，高mRNAsi组的免疫评分和基质评分较低。通过WGCNA获得了22个与干性相关的预后基因，这些基因主要集中在细胞周期和细胞有丝分裂的功能上。与高mRNAsi组相比，低mRNAsi组的免疫细胞浸润增加，尤其是CD8 + T细胞。高mRNAsi组中PD-L1、CTLA-4和TIGHT的表达较低。
高mRNAsi的ACC患者预后较差且免疫细胞浸润较少。结合高mRNAsi组中CTLA-4、TIGHT和PD-L1表达较低的发现，我们得出结论，干性指数是预测ICIs疗效的潜在生物标志物。
