Evolutionary selection identifies critical immune-relevant genes in lung cancer subtypes.
Evolutionary selection identifies critical immune-relevant genes in lung cancer subtypes.
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DOI：
10.3389/fgene.2022.921447
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发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
在进化的种群中，增殖依赖于适合度，因此数量占主导地位的种群通常拥有最适应的表型。相比之下，进化中的“失败者”通常会从种群中消失，因此他们的基因记录也会丢失。从历史上看，癌症研究的重点是观察到的主要肿瘤细胞群体中的基因突变，这些突变可能会增加适应性。负选择，即从种群中移除有害的突变，是不可观察到的，但可以提供有关参与基本细胞过程的基因的关键信息。与免疫编辑相似，“进化分类”消除了肿瘤细胞中增加对宿主免疫反应敏感性的突变，而保护它们免受免疫攻击的突变会增加增殖并容易观察到(例如，B2M突变)。这些动力学允许进行“逆问题”分析，将突变的适合性结果与其在肿瘤队列中的流行程度联系起来。这在“驱动突变”中很明显，但同样重要的是，它可以识别突变明显低于预期的必要基因。在这里，我们利用这种新的方法来研究TCGA肺腺癌队列中免疫相关基因的进化分类。负选择在两组人群中不同，内质网氨基肽酶基因、ERAP1和ERAP2基因以及dNaM-1/TIGIT配体被观察到。在积极或消极的进化选择下，靶向基因或分子通路可能会带来新的治疗选择，并增加当前免疫治疗的疗效。
In an evolving population, proliferation is dependent on fitness so that a numerically dominant population typically possesses the most well adapted phenotype. In contrast, the evolutionary “losers” typically disappear from the population so that their genetic record is lost. Historically, cancer research has focused on observed genetic mutations in the dominant tumor cell populations which presumably increase fitness. Negative selection, i.e., removal of deleterious mutations from a population, is not observable but can provide critical information regarding genes involved in essential cellular processes. Similar to immunoediting, “evolutionary triage” eliminates mutations in tumor cells that increase susceptibility to the host immune response while mutations that shield them from immune attack increase proliferation and are readily observable (e.g., B2M mutations). These dynamics permit an “inverse problem” analysis linking the fitness consequences of a mutation to its prevalence in a tumor cohort. This is evident in “driver mutations” but, equally important, can identify essential genes in which mutations are seen significantly less than expected by chance. Here we utilized this new approach to investigate evolutionary triage in immune-related genes from TCGA lung adenocarcinoma cohorts. Negative selection differs between the two cohorts and is observed in endoplasmic reticulum aminopeptidase genes, ERAP1 and ERAP2 genes, and DNAM-1/TIGIT ligands. Targeting genes or molecular pathways under positive or negative evolutionary selection may permit new treatment options and increase the efficacy of current immunotherapy.
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DOI：
10.1038/nrc3036
发表时间：
2011-04
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
22.7
作者：
Lehtiö J;Arslan T;Siavelis I;Pan Y;Socciarelli F;Berkovska O;Umer HM;Mermelekas G;Pirmoradian M;Jönsson M;Brunnström H;Brustugun OT;Purohit KP;Cunningham R;Foroughi Asl H;Isaksson S;Arbajian E;Aine M;Karlsson A;Kotevska M;Gram Hansen C;Drageset Haakensen V;Helland Å;Tamborero D;Johansson HJ;Branca RM;Planck M;Staaf J;Orre LM
通讯作者：
Orre LM
影响因子：
3.7
作者：
Hix LM;Shi YH;Brutkiewicz RR;Stein PL;Wang CR;Zhang M
通讯作者：
Zhang M
DOI：
10.1016/j.mrfmmm.2004.04.018
发表时间：
2004-12-21
影响因子：
2.3
作者：
Gatenby, RA;Frieden, BR
通讯作者：
Frieden, BR
影响因子：
2.7
作者：
Compagnone, Mirco;Cifaldi, Loredana;Fruci, Doriana
通讯作者：
Fruci, Doriana