Evolutionary genetic algorithm identifies IL2RB as a potential predictive biomarker for immune-checkpoint therapy in colorectal cancer.
Evolutionary genetic algorithm identifies IL2RB as a potential predictive biomarker for immune-checkpoint therapy in colorectal cancer.
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DOI：
10.1093/nargab/lqab016
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发表时间：
2021-06
影响因子：
4.6
通讯作者：
McArt DG
中科院分区：
文献类型：
--
作者：
Alderdice M;Craig SG;Humphries MP;Gilmore A;Johnston N;Bingham V;Coyle V;Senevirathne S;Longley DB;Loughrey MB;McQuaid S;James JA;Salto-Tellez M;Lawler M;McArt DG
根据结直肠癌(CRC)患者对免疫检查点治疗的反应，寻找强有力的预测生物标志物来对其进行分层是一个尚未得到满足的临床需求领域。我们的进化算法Atlas Relationship Explorer(ACE)代表了一种挖掘癌症基因组图谱(TCGA)数据以寻找临床相关关联的新方法。我们采用血管紧张素转换酶标记物来确定免疫检查点治疗对结直肠癌患者应答的候选预测生物标记物。我们通过9个免疫检查点(PDL1、PDCD1、CTLA4、LAG3、TIM3、TIGIT、ICOS、IDO1和BTLA)询问了结肠腺癌(CoAD)基因的表达数据。IL2RB基因是结直肠癌中最常见的与免疫检查点相关的基因。使用人/鼠单细胞核糖核酸序列数据，我们证明IL2RB主要在与免疫检查点表达增加相关的T细胞亚群中表达(P<0.0001)。在一个大型微卫星H结肠癌组织芯片中的验证性IL2RB免疫组织化学分析显示，一组淋巴细胞敏感、特异地染色，与FOXP3+淋巴细胞有很强的相关性(P<0.0001)。IL2RB mRNA与先前发表的免疫检查点治疗反应的三个基因信号呈正相关(P<0.0001)。我们的进化算法已发现IL2RB广泛与结直肠癌的免疫检查点相关；其表达作为接受免疫检查点阻断的结直肠癌患者的潜在预测生物标记物的临床实用价值应进行研究。
Identifying robust predictive biomarkers to stratify colorectal cancer (CRC) patients based on their response to immune-checkpoint therapy is an area of unmet clinical need. Our evolutionary algorithm Atlas Correlation Explorer (ACE) represents a novel approach for mining The Cancer Genome Atlas (TCGA) data for clinically relevant associations. We deployed ACE to identify candidate predictive biomarkers of response to immune-checkpoint therapy in CRC. We interrogated the colon adenocarcinoma (COAD) gene expression data across nine immune-checkpoints (PDL1, PDCD1, CTLA4, LAG3, TIM3, TIGIT, ICOS, IDO1 and BTLA). IL2RB was identified as the most common gene associated with immune-checkpoint genes in CRC. Using human/murine single-cell RNA-seq data, we demonstrated that IL2RB was expressed predominantly in a subset of T-cells associated with increased immune-checkpoint expression (P < 0.0001). Confirmatory IL2RB immunohistochemistry (IHC) analysis in a large MSI-H colon cancer tissue microarray (TMA; n = 115) revealed sensitive, specific staining of a subset of lymphocytes and a strong association with FOXP3+ lymphocytes (P < 0.0001). IL2RB mRNA positively correlated with three previously-published gene signatures of response to immune-checkpoint therapy (P < 0.0001). Our evolutionary algorithm has identified IL2RB to be extensively linked to immune-checkpoints in CRC; its expression should be investigated for clinical utility as a potential predictive biomarker for CRC patients receiving immune-checkpoint blockade.
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DOI：
10.1109/tvcg.2014.2346248
发表时间：
2014-12
影响因子：
5.2
作者：
Lex A;Gehlenborg N;Strobelt H;Vuillemot R;Pfister H
通讯作者：
Pfister H
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
4.6
作者：
Allen WL;Dunne PD;McDade S;Scanlon E;Loughrey M;Coleman H;McCann C;McLaughlin K;Nemeth Z;Syed N;Jithesh P;Arthur K;Wilson R;Coyle V;McArt D;Murray GI;Samuel L;Nuciforo P;Jimenez J;Argiles G;Dienstmann R;Tabernero J;Messerini L;Nobili S;Mini E;Sheahan K;Ryan E;Johnston PG;Van Schaeybroeck S;Lawler M;Longley DB
通讯作者：
Longley DB
DOI：
10.1002/path.5051
发表时间：
2018-05
期刊：
The Journal of pathology
影响因子：
--
作者：
Alderdice M;Richman SD;Gollins S;Stewart JP;Hurt C;Adams R;McCorry AM;Roddy AC;Vimalachandran D;Isella C;Medico E;Maughan T;McArt DG;Lawler M;Dunne PD
通讯作者：
Dunne PD
影响因子：
8.8
作者：
Dai, Z.;Zhang, S.;Li, X. C.
通讯作者：
Li, X. C.