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长链非编码RNA与转录组交集与转移性肾细胞癌靶向治疗反应的关联

Association of lncRNA and transcriptome intersections with response to targeted therapy in metastatic renal cell carcinoma.

作者信息

Tesarova Tereza, Koucka Kamila, Vaclavikova Radka, Seborova Karolina, Hora Milan, Hes Ondrej, Pivovarcikova Kristyna, Soucek Pavel, Fiala Ondrej

机构信息

Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic.

Toxicogenomics Unit, National Institute of Public Health, 100 00 Prague 10, Czech Republic.

出版信息

Oncol Lett. 2023 Jul 11;26(3):365. doi: 10.3892/ol.2023.13951. eCollection 2023 Sep.

Abstract

Long non-coding RNAs (lncRNAs) serve an important role in cancer progression and may be used as efficient molecular biomarkers. The present study aimed to identify lncRNAs associated with the response to the receptor tyrosine kinase inhibitor sunitinib and transcriptome profile and clinical features of metastatic renal cell carcinoma (mRCC). The gene expression of 84 cancer-associated lncRNAs in tumor and non-malignant tissue samples of 38 patients with mRCC was evaluated using quantitative PCR. In addition, the coding transcriptome was estimated using RNA sequencing in a subgroup of 20 patients and mRNA-lncRNA intersections were identified. In total, 37 and 13 lncRNAs were down- and upregulated, respectively, in tumor compared with non-malignant adjacent tissue samples. A total of 10 and 4 lncRNAs were up- and downregulated, respectively, in good responders to sunitinib compared with poor responders. High expression of HNF1A-AS1 and IPW lncRNAs was associated with prolonged progression-free survival of patients and a high expression of the TUSC7 lncRNA was associated with poor response and worse survival. Significant associations of dysregulated MEG3 and SNHG16 lncRNAs with expression of protein-coding genes representing various pathways, were identified. Furthermore, a significantly higher expression of gene was observed in good responders. The present study revealed promising candidates for predictive and prognostic biomarkers with further therapeutic potential.

摘要

长链非编码RNA(lncRNAs)在癌症进展中发挥重要作用,可作为有效的分子生物标志物。本研究旨在鉴定与受体酪氨酸激酶抑制剂舒尼替尼反应相关的lncRNAs以及转移性肾细胞癌(mRCC)的转录组谱和临床特征。使用定量PCR评估了38例mRCC患者肿瘤和非恶性组织样本中84种癌症相关lncRNAs的基因表达。此外,在20例患者的亚组中使用RNA测序估计编码转录组,并鉴定mRNA-lncRNA交叉点。与非恶性相邻组织样本相比,肿瘤中分别有37种和13种lncRNAs下调和上调。与舒尼替尼反应较差的患者相比,反应良好的患者中分别有10种和4种lncRNAs上调和下调。HNF1A-AS1和IPW lncRNAs的高表达与患者无进展生存期延长相关,而TUSC7 lncRNA的高表达与反应较差和生存期较差相关。鉴定出失调的MEG3和SNHG16 lncRNAs与代表各种途径的蛋白质编码基因表达之间的显著关联。此外,在反应良好的患者中观察到该基因的表达明显更高。本研究揭示了具有进一步治疗潜力的预测和预后生物标志物的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ba/10407709/04fe16decbc5/ol-26-03-13951-g00.jpg

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