Department of Biochemistry, Faculty of Pharmacy, Cairo University, 23 Kasr Al-Ainy street, Cairo, 11562, Egypt.
General Administration of Clinical Trials, Central Administration of Biological and Innovative Products and Clinical Studies, Egyptian Drug Authority, 51 Wezaret El Zeraa Street, Agouza, Giza, Egypt.
Sci Rep. 2021 Jan 22;11(1):2095. doi: 10.1038/s41598-021-81715-5.
The reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein-protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.
弥漫性大 B 细胞淋巴瘤（DLBCL）特异性靶标的可靠鉴定对其诊断和治疗具有重要意义。长链非编码 RNA（lncRNA）参与 DLBCL 的发病机制；然而，循环 DLBCL 相关的 lncRNA 很少被研究。我们研究了血浆 lncRNA；HOTAIR、Linc-p21、GAS5 和 XIST 作为 DLBCL 诊断和对 R-CHOP 治疗反应性的生物标志物。纳入 84 例 DLBCL 患者和 33 名健康对照者。与对照组相比，只有血浆 HOTAIR、XIST 和 GAS5 在 DLBCL 患者中差异表达。非 R-CHOP 应答者的血浆 HOTAIR 水平较高，而 GAS5 水平较低。血浆 GAS5 表现出较高的诊断准确性（AUC=0.97），而 HOTAIR+GAS5 联合分析可更好地区分 R-CHOP 应答者和非应答者。多变量分析表明，HOTAIR 是无反应的独立预测因子。在患者中，血浆 HOTAIR、Linc-p21 和 XIST 之间存在相关性。血浆 GAS5 与国际预后指数呈负相关，而 HOTAIR 与体能状态呈正相关，提示其具有预后潜力。我们通过生物信息学分析构建了与药物反应相关的 lncRNAs 相关的蛋白质-蛋白质相互作用网络。总之，我们提出了血浆 HOTAIR、GAS5 和 XIST 作为潜在的非侵入性诊断工具用于 DLBCL，以及预处理 HOTAIR 和 GAS5 作为评估治疗反应的候选物，HOTAIR 作为 R-CHOP 失败的预测因子。我们为个性化医学的未来预测研究提供了新的替代物。
