LncRNA NNT-AS1/hsa-miR-485-5p/HSP90 轴的计算机预测与临床相关性分析及其与 CRC 组织学分级的分层：迈向 ncRNA 精准治疗的一步
LncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis in-silico and clinical prospect correlated-to histologic grades-based CRC stratification: A step toward ncRNA Precision.
机构信息
Biochemistry Department, Faculty of Pharmacy, Heliopolis University, El Salam City, 11785 Cairo, Egypt.
Biochemistry Department, Faculty of Pharmacy, Heliopolis University, El Salam City, 11785 Cairo, Egypt; Biochemistry Department, Faculty of Pharmacy (Boy's Branch), Al-Azhar University, Nasr City, 11884 Cairo, Egypt.
出版信息
Pathol Res Pract. 2023 Jul;247:154570. doi: 10.1016/j.prp.2023.154570. Epub 2023 May 24.
The oncogenic effects of long non-coding RNA (lncRNA) Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) role in colorectal cancer (CRC) hasn't been sufficiently inspected in relation to the Homo sapiens (hsa)-microRNA (miR)- 485-5p/ heat shock protein 90 (HSP90) axis, clinically. qRT-PCR was performed to detect lncRNA NNT-AS1 and hsa-miR-485-5p expression levels in 60 Egyptian patients' sera. HSP90 serum level was quantified using Enzyme-linked immunosorbent assay (ELISA). The relative expression level of the studied non-coding RNAs as well as the HSP90 ELISA concentration were correlated with patients clinicopathological characteristics and correlated to each other. The axis diagnostic utility in comparison with carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) tumor markers (TMs) was studied by receiver operating characteristic (ROC) curve analysis. The relative lncRNA NNT-AS1 expression level fold change 56.7 (13.5-112) and HSP90 protein ELISA level 6.68 (5.14-8.77) (ng/mL) were elevated, while, for hsa-miR-485-5p 0.0474 (0.0236-0.135) expression fold change was repressed in CRC Egyptian patients' cohort sera, being compared to 28 apparently healthy control subjects. LncRNA NNT-AS1 specificity is 96.4% and a sensitivity of 91.7%, hsa-miR-485-5p showed 96.4% specificity, 90% sensitivity, and for HSP90 89.3%, 70% specificity and sensitivity, respectively. Those specificities and sensitivities were superior to the classical CRC TMs. A significant negative correlation was found between hsa-miR-485-5p with lncRNA NNT-AS1 (r = -0.933) expression fold change or with HSP90 protein blood level (r = -0.997), but, significant positive correlation was there between lncRNA NNT-AS1 and HSP90 (r = 0.927). LncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis could be a prospect for CRC development as well as diagnosis. Being correlated and related to CRC histologic grades 1-3, therefore, lncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis (not individually) expression approved clinically and in silico, could aid treatment precision.
长链非编码 RNA (lncRNA) 烟酰胺核苷酸转氢酶反义 RNA1 (NNT-AS1) 在结直肠癌 (CRC) 中的致癌作用与 Homo sapiens (hsa)-microRNA (miR)-485-5p/热休克蛋白 90 (HSP90) 轴的关系尚未得到充分研究。我们通过 qRT-PCR 检测了 60 例埃及患者血清中的 lncRNA NNT-AS1 和 hsa-miR-485-5p 表达水平。采用酶联免疫吸附试验 (ELISA) 定量检测 HSP90 血清水平。研究了这些非编码 RNA 的相对表达水平以及 HSP90 ELISA 浓度与患者临床病理特征的相关性，并相互关联。通过受试者工作特征 (ROC) 曲线分析研究了该轴与癌胚抗原 19-9 (CA19-9) 和癌胚抗原 (CEA) 肿瘤标志物 (TM) 的诊断效用。与 28 名明显健康的对照相比，CRC 埃及患者队列血清中相对 lncRNA NNT-AS1 表达水平的变化倍数为 56.7(13.5-112)，HSP90 蛋白 ELISA 水平为 6.68(5.14-8.77)(ng/mL)，而 hsa-miR-485-5p 的表达水平为 0.0474(0.0236-0.135)。lncRNA NNT-AS1 的特异性为 96.4%，灵敏度为 91.7%，hsa-miR-485-5p 的特异性为 96.4%，灵敏度为 90%，HSP90 的特异性为 89.3%，灵敏度为 70%。这些特异性和敏感性优于经典的 CRC TMs。hsa-miR-485-5p 与 lncRNA NNT-AS1(r=-0.933)表达水平的变化或与 HSP90 蛋白血水平(r=-0.997)之间存在显著负相关，但 lncRNA NNT-AS1 与 HSP90 之间存在显著正相关(r=0.927)。lncRNA NNT-AS1/hsa-miR-485-5p/HSP90 轴可能是 CRC 发展和诊断的一个前景。lncRNA NNT-AS1/hsa-miR-485-5p/HSP90 轴与 CRC 组织学分级 1-3 相关，因此，lncRNA NNT-AS1/hsa-miR-485-5p/HSP90 轴(而非单独)的表达在临床上和计算机上都得到了证实，这可能有助于提高治疗的准确性。
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