Abstract：
Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers. After escaping death, cancer cells are made more metastatic, aggressive, and also drug-resistant through anoikis resistance. The aim of this study is to explore the molecular mechanisms of anoikis-related genes in PAAD and to identify potential key biomarkers. We integrated information about PAAD from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases and identified anoikis-related gene BCL2L1 by survival analysis, univariate Cox regression analysis, and multifactorial Cox regression analysis. Various bioinformatics approaches showed that BCL2L1 was a valuable prognostic marker that might be involved in PAAD development and progression through different mechanisms, including cancer intervention, genomic heterogeneity, and RNA modifications. Our analysis showed that BCL2L1 expression also closely correlates with the expression of various immune checkpoint inhibitors. In particular, we found that long non-coding RNA MIR4435-2HG acted as ceRNA sponging miR-513a-5p to promote the expression of BCL2L1, thereby promoting pancreatic cancer cells proliferation. In conclusion, BCL2L1 expression regulated by the MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis might be used as a biomarker for cancer prognosis, treatment selection, and follow-up in PAAD patients.
摘要：
胰腺癌(PAAD)是最恶性的癌症之一。逃离死亡后，癌细胞变得更具转移性，侵略性,也通过抗肛门凋亡产生抗药性。本研究的目的是探索PAAD中失巢凋亡相关基因的分子机制，并确定潜在的关键生物标志物。我们整合了来自癌症基因组图谱（TCGA）和基因型组织表达（GTEx）数据库的有关PAAD的信息，并通过生存分析鉴定了与失巢凋亡相关的基因BCL2L1。单变量Cox回归分析，和多因素Cox回归分析。各种生物信息学方法表明，BCL2L1是一个有价值的预后标志物，可能通过不同的机制参与PAAD的发生和发展。包括癌症干预，基因组异质性，和RNA修饰。我们的分析表明，BCL2L1的表达也与各种免疫检查点抑制剂的表达密切相关。特别是,我们发现长链非编码RNAMIR4435-2HG充当ceNRNA,将miR-513a-5p促进BCL2L1的表达,从而促进胰腺癌细胞增殖.总之,由MIR4435-2HG-miR-513a-5p-BCL2L1ceRNA轴调节的BCL2L1表达可能用作癌症预后的生物标志物。治疗选择，并对PAAD患者进行随访。
