内含子多态性与转录本增加、免疫浸润及癌症风险相关。
Intronic Polymorphisms Are Associated with Increased Transcript, Immune Infiltration and Cancer Risk.
作者信息
Eiholzer Ramona A, Mehta Sunali, Kazantseva Marina, Drummond Catherine J, McKinney Cushla, Young Katie, Slater David, Morten Brianna C, Avery-Kiejda Kelly A, Lasham Annette, Fleming Nicholas, Morrin Helen R, Reader Karen, Royds Janice A, Landmann Michael, Petrich Simone, Reddel Roger, Huschtscha Lily, Taha Ahmad, Hung Noelyn A, Slatter Tania L, Braithwaite Antony W
机构信息
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, Dunedin 9016, New Zealand.
出版信息
Cancers (Basel). 2020 Sep 1;12(9):2472. doi: 10.3390/cancers12092472.
We investigated the influence of selected SNPs in exon 4 and intron 4 on cancer risk, clinicopathological features and expression of isoforms. The intron 4 SNPs were significantly over-represented in cohorts of mixed cancers compared to three ethnically matched controls, suggesting they confer increased cancer risk. Further analysis showed that heterozygosity at rs1042522(GC) and either of the two intronic SNPs rs9895829(TC) and rs2909430(AG) confer a 2.34-5.35-fold greater risk of developing cancer. These SNP combinations were found to be associated with shorter patient survival for glioblastoma and prostate cancer. Additionally, these SNPs were associated with tumor-promoting inflammation as evidenced by high levels of infiltrating immune cells and expression of the and transcripts. We propose that these SNP combinations allow increased expression of the Δ133p53 isoforms to promote the recruitment of immune cells that create an immunosuppressive environment leading to cancer progression.
我们研究了外显子4和内含子4中选定的单核苷酸多态性（SNP）对癌症风险、临床病理特征及异构体表达的影响。与三个种族匹配的对照组相比，内含子4的SNP在混合癌症队列中显著过度出现，表明它们会增加癌症风险。进一步分析显示，rs1042522（GC）处的杂合性以及两个内含子SNP rs9895829（TC）和rs2909430（AG）中的任何一个会使患癌风险增加2.34至5.35倍。这些SNP组合被发现与胶质母细胞瘤和前列腺癌患者的较短生存期相关。此外，这些SNP与肿瘤促进性炎症相关，高浸润免疫细胞水平以及相关转录本的表达证明了这一点。我们提出，这些SNP组合会使Δ133p53异构体的表达增加，从而促进免疫细胞的募集，营造出导致癌症进展的免疫抑制环境。
Zotero 插件