Barani Ali, Beikverdi Kamyar, Mashhadi Benyamin, Parsapour Naeimeh, Rezaei Mohammad, Javid Pegah, Azadeh Mansoureh
Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran.
Department of Biosciences, University of Milan, Milan, Italy.
Int J Genomics. 2023 Dec 22;2023:5583231. doi: 10.1155/2023/5583231. eCollection 2023.
Gastric cancer (GC) is the second most frequent cause of cancer-related death worldwide and the fourth most common malignancy. Despite significant improvements in patient survival over the past few decades, the prognosis for patients with GC remains dismal because of the high recurrence rate. In this comprehensive system biology and experimental investigation, we aimed to find new novel diagnostic biomarkers of GC through a regulatory RNA interaction network.
Gene expression, coexpression, and survival analyses were performed using microarray and RNAseq datasets (analyzed by RStudio, GEPIA2, and ENCORI). RNA interaction analysis was performed using miRWalk and ENCORI online databases. Gene set enrichment analysis (GSEA) was performed to find related signaling pathways of up- and downregulated genes in the microarray dataset. Gene ontology and pathway enrichment analysis were performed by the enrichr database. Protein interaction analysis was performed by STRING online database. Validation of expression and coexpression analyses was performed using a qRT-PCR experiment.
Based on bioinformatics analyses, (FC: 7.14, FDR < 0.0001) has a significantly high expression in GC samples. lncRNAs , , and have RNA interaction with . (FC: 1.44, FDR: 0.018), (FC: 1.34, FDR: 0.038), and (FC: 1.19, FDR: 0.046) have significant upregulation in GC samples. has a significant role in the regulation of the ECM-receptor signaling pathway. miR-4677-5p has a significant RNA interaction with . The expression level of , , , and has a nonsignificant negative correlation with the survival rate of GC patients (HR: 0.28, logrank : 0.28). qRT-PCR experiment validates mentioned bioinformatics expression analyses. (AUC: 0.7136, value: 0.0096), (AUC: 0.7456, value: 0.0029), and (AUC: 0.7872, value: 0.0005) could be acceptable diagnostic biomarkers of GC.
, lncRNA , lncRNA , and miR-4677-5p might modulate the ECM-receptor signaling pathway via regulation of expression level, as the high-expressed noncoding RNAs in GC. Furthermore, mentioned lncRNAs could be considered potential diagnostic biomarkers of GC.
胃癌（GC）是全球癌症相关死亡的第二大常见原因，也是第四大常见恶性肿瘤。尽管在过去几十年中患者生存率有了显著提高，但由于高复发率，GC患者的预后仍然不佳。在这项全面的系统生物学和实验研究中，我们旨在通过调控RNA相互作用网络寻找GC新的诊断生物标志物。
使用微阵列和RNA测序数据集（由RStudio、GEPIA2和ENCORI分析）进行基因表达、共表达和生存分析。使用miRWalk和ENCORI在线数据库进行RNA相互作用分析。进行基因集富集分析（GSEA）以找到微阵列数据集中上调和下调基因的相关信号通路。通过enrichr数据库进行基因本体和通路富集分析。通过STRING在线数据库进行蛋白质相互作用分析。使用qRT-PCR实验验证表达和共表达分析。
基于生物信息学分析，（FC：7.14，FDR < 0.0001）在GC样本中具有显著高表达。lncRNAs 、 和 与 存在RNA相互作用。（FC：1.44，FDR：0.018）、（FC：1.34，FDR：0.038）和（FC：1.19，FDR：0.046）在GC样本中显著上调。 在细胞外基质受体信号通路的调控中起重要作用。miR-4677-5p与 存在显著的RNA相互作用。 、 、 和 的表达水平与GC患者的生存率呈非显著负相关（HR：0.28，对数秩：0.28）。qRT-PCR实验验证了上述生物信息学表达分析。（AUC：0.7136， 值：0.0096）、（AUC：0.7456， 值：0.0029）和（AUC：0.7872， 值：0.0005）可能是GC可接受的诊断生物标志物。
、lncRNA 、lncRNA 和miR-4677-5p可能通过调节 的表达水平来调节细胞外基质受体信号通路，作为GC中高表达的非编码RNA。此外，上述lncRNAs可被视为GC潜在的诊断生物标志物。
