摘要
      失活细胞是一种特殊的程序性细胞死亡模式，对失活细胞的抵抗是恶性肿瘤获得侵袭和转移特征的先决条件。失巢相关基因（ARGs）在宫颈癌症（CC）中的表达及其影响尚不清楚。本研究的目的是揭示ARGs在CC患者生存、免疫浸润和药物敏感性中的预后作用，并确定潜在的临床治疗靶点。从TCGA数据库和GEO数据库下载CC患者的RNA-seq和临床数据，从UCSC下载基因拷贝数据。生物信息学方法用于筛选与预后相关的差异表达ARG，并使用R软件包和Perl软件进行数据分析。TISCH数据库用于在单细胞水平上分析ARGs在肿瘤微环境（TME）中的表达。11号染色体上的MMP3在CC组织中高度表达，可能是CC进展的关键基因。细胞周期素-细胞周期素受体相互作用、ECM受体相互作用，JAK-STAT信号通路和局灶性粘附通路的显著激活可能与CC患者的不良预后有关。CD8的减少 + T细胞和M0巨噬细胞的增加可能预示着患者的高危预后。Bcl-2抑制剂（ABT-737）、阿西替尼、二氢鱼藤酮、索拉非尼、venetoclax和尼洛替尼是CC早期治疗的可选药物。未来，基于ARGs的miRNA、小分子药物/抑制剂、肽/蛋白特异性疗法和特异性抗体可能会被开发用于CC的早期诊断和临床治疗。
Abstract
Anoikis is a special programmed cell death mode, and resistance to anoikis is a prerequisite for malignant tumors to acquire invasion and metastasis characteristics. The expression and impact of anoikis-related genes (ARGs) in cervical cancer (CC) are still unknown. The aim of this study is to reveal the prognostic role of ARGs in survival, immune infiltration, and drug sensitivity of CC patients, and to identify potential clinical treatment targets. RNA seq and clinical data of CC patients were downloaded from the TCGA database and GEO database, and gene copy data was downloaded from UCSC. Bioinformatics methods was used to screen differentially expressed ARGs related to prognosis, and conducting data analysis using R software package and Perl software. TISCH database was used to analyze the expression of ARGs in tumor microenvironment (TME) at the single cell level. MMP3 on chromosome 11 is highly expressed in CC tissue and may be a key gene for CC progression. The significant activation of the cycline-cycline receptor interaction, ECM-receptor interaction, JAK-STAT signaling pathway, and focal adhesion pathway may be associated with poor prognosis in CC patients. The decrease in CD8 + T cells and the increase in M0 macrophages may indicate a high-risk prognosis for patients. Bcl-2 inhibitor (ABT-737), axitinib, dihydrorotenone, sorafenib, venetoclax, and nilotinib are optional drugs for early treatment of CC. In the future, ARGs based miRNAs, small molecule drugs/inhibitors, peptide/protein specific therapies, and specific antibodies may be developed for early diagnosis and clinical treatment of CC.

https://www.researchsquare.com/article/rs-2813411/v1