Pancreatic adenocarcinoma (PAAD) is a malignant tumor of the digestive system, which develops rapidly and has no obvious early symptoms. This study aims to discover the biomarkers associated with PAAD development. We obtained RNA expression of PAAD patient samples and corresponding clinical data from The cancer genome atlas (TCGA), and screened out BMP/RA-inducible neural-specific protein 2 (BRINP2) gene which is highly associated with PAAD severity. Then, gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and single-sample gene set enrichment analysis (ssGSEA) analysis were performed to explore the biological functions of BRINP2. Subsequently, long non-coding RNA (lncRNAs) associated with BRINP2 were screened out via correlation analysis, and Cox regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were used to construct the risk prediction model. We further validated the expression level of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in vitro. We proposed that BRINP2 might be correlated to the tumor immune microenvironment and could also be used as a biomarker for PAAD progression. GO enrichment analysis and KEGG pathway analysis showed that the prognostic model was highly correlated to immune microenvironment-related pathways. Additionally, we established a BRINP2-associated lncRNAs prognostic model consisting of three lncRNAs. We validated the expression trends of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in PAAD cells with various severity of metastatic potential using the quantitative real-time PCR (qRT-PCR). Meanwhile, pRRophetic R package was employed to predict potential therapeutic drugs for BRINP2-associated lncRNAs prognostic model of PAAD. The results suggest that BRINP2 can be used as a novel prognostic biomarker for PAAD.

中文翻译：

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基于胰腺癌进展的系统分析将 BRINP2 确定为新型预后生物标志物

胰腺癌（PAAD）是一种消化系统恶性肿瘤，发展迅速，早期无明显症状。本研究旨在发现与 PAAD 发展相关的生物标志物。我们从癌症基因组图谱（TCGA）中获得了PAAD患者样本的RNA表达和相应的临床数据，并筛选出与PAAD严重程度高度相关的BMP/RA诱导神经特异性蛋白2（BRINP2）基因。然后，进行基因本体（GO）富集、京都基因和基因组百科全书（KEGG）通路分析和单样本基因集富集分析（ssGSEA）分析来探索BRINP2的生物学功能。随后，通过相关性分析筛选出与BRINP2相关的长链非编码RNA（lncRNA），并利用Cox回归分析和最小绝对收缩选择算子（LASSO）回归分析构建风险预测模型。我们进一步验证了BRINP2相关lncRNA体外预后模型中BRINP2及其相关lncRNA的表达水平。我们提出BRINP2可能与肿瘤免疫微环境相关，也可以用作PAAD进展的生物标志物。GO富集分析和KEGG通路分析表明，预后模型与免疫微环境相关通路高度相关。此外，我们建立了由三个 lncRNA 组成的 BRINP2 相关 lncRNA 预后模型。我们使用定量实时 PCR (qRT-PCR) 验证了具有不同转移潜能严重程度的 PAAD 细胞中 BRINP2 相关 lncRNA 预后模型中 BRINP2 及其相关 lncRNA 的表达趋势。同时，采用pRRophetic R 包来预测 BRINP2 相关 lncRNA 的 PAAD 预后模型的潜在治疗药物。结果表明 BRINP2 可用作 PAAD 的新型预后生物标志物。