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pmid:33330048

Identification of an Immune-Related Gene Signature Based on Immunogenomic Landscape Analysis to Predict the Prognosis of Adult Acute Myeloid Leukemia Patients.

Ruiqi Zhu · Huishan Tao · Wenyi Lin · Liang Tang · Yu Hu

Frontiers in oncology · 2020 doi:10.3389/fonc.2020.574939

Paper

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Experiment

complete

Data

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pmid:33330048
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title
Identification of an Immune-Related Gene Signature Based on Immunogenomic Landscape Analysis to Predict the Prognosis of Adult Acute Myeloid Leukemia Patients.
doi
10.3389/fonc.2020.574939
pmid
33330048
authors array · 5 items
[0]
Ruiqi Zhu
[1]
Huishan Tao
[2]
Wenyi Lin
[3]
Liang Tang
[4]
Yu Hu
journal
Frontiers in oncology
year
2020
abstract
Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by highly heterogeneous molecular lesions and cytogenetic abnormalities. Immune disorders in AML and impaired immune cell function have been found to be associated with abnormal karyotypes in AML patients. Immunotherapy has become an alternative therapeutic method that can improve the outcomes of AML patients. For solid tumors, the expression patterns of genes associated with the immune microenvironment provide valuable prognostic information. However, the prognostic roles of immune genes in AML have not been studied as yet. In this study, we identified 136 immune-related genes associated with overall survival in AML patients through a univariate Cox regression analysis using data from TCGA-AML and GTEx datasets. Next, we selected 24 hub genes from among the 136 genes based on the PPI network analysis. The 24 immune-related hub genes further underwent multivariate Cox regression analysis and LASSO regression analysis. Finally, a 6 immune-related gene signature was constructed to predict the prognosis of AML patients. The function of the hub IRGs and the relationships between hub IRGs and transcriptional factors were investigated. We found that higher levels of expression of CSK, MMP7, PSMA7, PDCD1, IKBKG, and ISG15 were associated with an unfavorable prognosis of AML patients. Meanwhile, patients in the TCGA-AML datasets were divided into a high risk score group and a low risk score group, based on the median risk score value. Patients in the high risk group tended to show poorer prognosis [P = 0.00019, HR = 1.89 (1.26-2.83)]. The area under the curve (AUC) was 0.6643. Multivariate Cox Regression assay confirmed that the 6 IRG signature was an independent prognostic factor for AML. The prognostic role of the immune related-gene signature was further validated using an independent AML dataset, GSE37642. In addition, patients in the high risk score group in the TCGA dataset were found to be of an advanced age, IDH mutation, and M5 FAB category. These results suggested that the proposed immune related-gene signature may serve as a potential prognostic tool for AML patients.
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The Kaplan-Meier curve was used to show differences in OS between the high-risk group and low-risk group patients, based on the IRG signature.
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sections[8] "Statistical Analysis" paragraph 2
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The Kaplan-Meier curve was used to show differences in OS between the high-risk group and low-risk group patients, based on the IRG signature.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .
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sections[18] "Data Availability Statement" paragraph 2
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .
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https://doi.org/10.3389/fonc.2020.574939
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GSM924089
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GSM924091
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GSM924092
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[506]
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[512]
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[513]
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[514]
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[515]
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[516]
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[517]
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[518]
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[519]
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[520]
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[522]
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[523]
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[524]
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[525]
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[526]
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[527]
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[528]
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[529]
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[530]
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[532]
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[533]
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[534]
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[535]
GSM924131
[536]
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[537]
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[538]
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[539]
GSM924135
[540]
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[541]
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[542]
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[543]
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[544]
GSM924140
[545]
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[546]
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[547]
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[548]
GSM924144
[549]
GSM924145
[550]
GSM924146
[551]
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[552]
GSM924148
[553]
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[554]
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[555]
GSM924151
[556]
GSM924152
[557]
GSM924153
[558]
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[559]
GSM924155
[560]
GSM924156
[561]
GSM924157
[562]
GSM924158
[563]
GSM924159
[564]
GSM924160
[565]
GSM924161
[566]
GSM924162
[567]
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[568]
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[571]
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[583]
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[591]
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[592]
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[593]
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[594]
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[595]
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[596]
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[597]
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[598]
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[599]
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[600]
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[601]
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[602]
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[603]
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[604]
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[605]
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[606]
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[607]
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[608]
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[609]
GSM924205
[610]
GSM924206
[611]
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[612]
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[613]
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[614]
GSM924210
[615]
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[616]
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[617]
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[618]
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[625]
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[626]
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[627]
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[628]
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[629]
GSM924225
[630]
GSM924226
[631]
GSM924227
[632]
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[633]
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[634]
GSM924230
[635]
GSM924231
[636]
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[637]
GSM924233
[638]
GSM924234
[639]
GSM924235
[640]
GSM924236
[641]
GSM924237
[642]
GSM924238
[643]
GSM924239
[644]
GSM924240
[645]
GSM924241
[646]
GSM924242
[647]
GSM924243
[648]
GSM924244
[649]
GSM924245
[650]
GSM924246
[651]
GSM924247
[652]
GSM924248
[653]
GSM924249
[654]
GSM924250
[655]
GSM924251
[656]
GSM924252
[657]
GSM924253
[658]
GSM924254
[659]
GSM924255
[660]
GSM924256
[661]
GSM924257
[662]
GSM924258
[663]
GSM924259
[664]
GSM924260
[665]
GSM924261
[666]
GSM924262
[667]
GSM924263
[668]
GSM924264
[669]
GSM924265
[670]
GSM924266
[671]
GSM924267
[672]
GSM924268
[673]
GSM924269
[674]
GSM924270
[675]
GSM924271
[676]
GSM924272
[677]
GSM924273
[678]
GSM924274
[679]
GSM924275
[680]
GSM924276
[681]
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[682]
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[683]
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[684]
GSM924280
[685]
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[686]
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[687]
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[688]
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[689]
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[690]
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[691]
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[692]
GSM924288
[693]
GSM924289
[694]
GSM924290
[695]
GSM924291
[696]
GSM924292
[697]
GSM924293
[698]
GSM924294
[699]
GSM924295
[700]
GSM924296
[701]
GSM924297
[702]
GSM924298
[703]
GSM924299
[704]
GSM924300
[705]
GSM924301
[706]
GSM924302
[707]
GSM924303
[708]
GSM924304
[709]
GSM924305
[710]
GSM924306
[711]
GSM924307
[712]
GSM924308
[713]
GSM924309
[714]
GSM924310
[715]
GSM924311
[716]
GSM924312
[717]
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[718]
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[719]
GSM924315
[720]
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[721]
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[722]
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[723]
GSM924319
[724]
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[725]
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[726]
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[727]
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[728]
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[729]
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[730]
GSM924326
[731]
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[732]
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[733]
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[734]
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[735]
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[736]
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[737]
GSM924333
[738]
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[739]
GSM924335
[740]
GSM924336
[741]
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[742]
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[743]
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[744]
GSM924340
[745]
GSM924341
[746]
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[747]
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[748]
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[749]
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[750]
GSM924346
[751]
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[752]
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[753]
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[754]
GSM924350
[755]
GSM924351
[756]
GSM924352
[757]
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[758]
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[759]
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[760]
GSM924356
[761]
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[762]
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[763]
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[771]
GSM924367
[772]
GSM924368
[773]
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[774]
GSM924370
[775]
GSM924371
[776]
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[777]
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[778]
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[779]
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[780]
GSM924376
[781]
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[782]
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[783]
GSM924379
[784]
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[785]
GSM924381
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[787]
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[788]
GSM924384
[789]
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[791]
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[792]
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[793]
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[794]
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[796]
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[797]
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[798]
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[799]
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[800]
GSM924396
[801]
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[802]
GSM924398
[803]
GSM924399
[804]
GSM924400
[805]
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[806]
GSM924402
[807]
GSM924403
[808]
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[809]
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[810]
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[842]
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[843]
GSM924439
[844]
GSM924440
[845]
GSM924441
[846]
GSM924442
[847]
GSM924443
[848]
GSM924444
[849]
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[850]
GSM924446
[851]
GSM924447
[852]
GSM924448
[853]
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[854]
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[856]
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[857]
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[858]
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[859]
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[860]
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[861]
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[862]
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[863]
GSM924459
[864]
GSM924460
[865]
GSM924461
[866]
GSM924462
[867]
GSM924463
[868]
GSM924464
[869]
GSM924465
[870]
GSM924466
[871]
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[872]
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[874]
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[892]
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[893]
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[894]
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[895]
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GSM924493
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[899]
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[900]
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[901]
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[902]
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[903]
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[904]
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[905]
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[906]
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[910]
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[911]
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[912]
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[913]
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[914]
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[915]
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[916]
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[917]
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[918]
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[933]
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GSM924533
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[942]
GSM924538
[943]
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GSM924576
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GSM924577
[982]
GSM924578
[983]
GSM924579
sample_count
984
group_sizes
null
group_sizes_basis
null
platform
570;96;97
taxon
Homo sapiens
title
Prognostic gene signature for AML
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[2] object · 16 fields
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asset:table:pmid:33330048:1
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table
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jats-table
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application/vnd.jats.table+json
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null
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sha256:25918d66a4d752c3ee9d6cedcfc8530f4c64d764b4e975a8a8821ebc1d4a5db6
bytes
1166
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open
state
verified
reader
read_table
reader_status
available
identifier
section[3]/table-wrap[1]#T1
version
null
note
Clinical characteristics of patients in TCGA-LAML dataset.
structure object · 5 fields
pmcid
PMC7714942
section_index
3
section_title
Data Collection From Publicly Available Databases
row_count
40
column_count
3
table object · 8 fields
label
Table 1
caption
Clinical characteristics of patients in TCGA-LAML dataset.
rows array · 40 items
[0] array · 3 items
[0]
Discrete variables
[1]
Number
[2]
Percentage (%)
[1] array · 1 item
[0]
Gender
[2] array · 3 items
[0]
Male
[1]
78
[2]
54.55
[3] array · 3 items
[0]
Female
[1]
65
[2]
45.45
[4] array · 1 item
[0]
FAB subtype
[5] array · 3 items
[0]
M0
[1]
15
[2]
10.49
[6] array · 3 items
[0]
M1
[1]
36
[2]
25.17
[7] array · 3 items
[0]
M2
[1]
35
[2]
24.48
[8] array · 3 items
[0]
M4
[1]
34
[2]
23.78
[9] array · 3 items
[0]
M5
[1]
18
[2]
12.59
[10] array · 3 items
[0]
M6
[1]
2
[2]
1.4
[11] array · 3 items
[0]
M7
[1]
3
[2]
2.1
[12] array · 1 item
[0]
Karyotype
[13] array · 3 items
[0]
Favorable
[1]
17
[2]
11.89
[14] array · 3 items
[0]
Intermediate
[1]
94
[2]
65.73
[15] array · 3 items
[0]
Poor
[1]
30
[2]
20.98
[16] array · 3 items
[0]
Unknown
[1]
2
[2]
1.4
[17] array · 3 items
[0]
Living status
[1]
[2]
[18] array · 3 items
[0]
Dead
[1]
97
[2]
67.83
[19] array · 3 items
[0]
Alive
[1]
46
[2]
32.17
[20] array · 1 item
[0]
IDH mutation
[21] array · 3 items
[0]
Positive
[1]
27
[2]
18.88
[22] array · 3 items
[0]
Negative
[1]
114
[2]
79.72
[23] array · 3 items
[0]
Unknown
[1]
2
[2]
1.4
[24] array · 1 item
[0]
FLT3 mutation
[25] array · 3 items
[0]
Positive
[1]
35
[2]
24.48
[26] array · 3 items
[0]
Negative
[1]
101
[2]
70.63
[27] array · 3 items
[0]
Unknown
[1]
7
[2]
4.9
[28] array · 3 items
[0]
RAS mutation
[1]
[2]
[29] array · 3 items
[0]
Positive
[1]
8
[2]
5.59
[30] array · 3 items
[0]
Negative
[1]
132
[2]
92.31
[31] array · 3 items
[0]
Unknown
[1]
3
[2]
2.1
[32] array · 1 item
[0]
NPM1 mutation
[33] array · 3 items
[0]
Positive
[1]
42
[2]
29.37
[34] array · 3 items
[0]
Negative
[1]
98
[2]
68.53
[35] array · 3 items
[0]
Unknown
[1]
3
[2]
[36] array · 3 items
[0]
Continuous Variables
[1]
Range
[2]
Median
[37] array · 3 items
[0]
Age (years)
[1]
18–88
[2]
60
[38] array · 3 items
[0]
Overall survival (days)
[1]
0–2861
[2]
334
[39] array · 3 items
[0]
WBC (10^9/L)
[1]
1–297
[2]
18
locator
section[3]/table-wrap[1]#T1
[3] object · 16 fields
id
asset:table:pmid:33330048:2
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:922cfa666c0cdf03563a2be5f19be82600178006b25faebf15a242e9afffe7f8
bytes
572
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[15]/table-wrap[1]#T2
version
null
note
Clinical variables in patients of GSE37642.
structure object · 5 fields
pmcid
PMC7714942
section_index
15
section_title
Prognostic Signature Construction Using Hub IRGs
row_count
15
column_count
3
table object · 8 fields
label
Table 2
caption
Clinical variables in patients of GSE37642.
rows array · 15 items
[0] array · 3 items
[0]
Discrete Variables
[1]
Number
[2]
Percentage (%)
[1] array · 1 item
[0]
FAB subtype
[2] array · 3 items
[0]
M0
[1]
8
[2]
6.25
[3] array · 3 items
[0]
M1
[1]
29
[2]
22.66
[4] array · 3 items
[0]
M2
[1]
47
[2]
36.72
[5] array · 3 items
[0]
M4
[1]
17
[2]
13.28
[6] array · 3 items
[0]
M5
[1]
19
[2]
14.84
[7] array · 3 items
[0]
M6
[1]
7
[2]
5.47
[8] array · 3 items
[0]
M7
[1]
1
[2]
0.78
[9] array · 1 item
[0]
Living Status
[10] array · 3 items
[0]
Dead
[1]
95
[2]
74.22
[11] array · 3 items
[0]
Alive
[1]
33
[2]
25.78
[12] array · 3 items
[0]
Continuous Variables
[1]
Range
[2]
Median
[13] array · 3 items
[0]
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[2]
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[0]
Overall Survival (days)
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[2]
402
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section[15]/table-wrap[1]#T2
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Multivariate Cox Regression assay for OS using known clinical prognosticators and 6 IRG risk score.
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pmcid
PMC7714942
section_index
15
section_title
Prognostic Signature Construction Using Hub IRGs
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12
column_count
5
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Table 3
caption
Multivariate Cox Regression assay for OS using known clinical prognosticators and 6 IRG risk score.
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[0]
[1]
[2]
[3]
95% Exp(B) CI
[1] array · 5 items
[0]
Variable
[1]
P-value
[2]
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[3]
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[4]
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[0]
Age
[1]
0.001
[2]
3.428
[3]
2.061
[4]
5.701
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[0]
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0.646
[2]
0.892
[3]
0.548
[4]
1.452
[4] array · 5 items
[0]
WBC
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0.587
[2]
0.872
[3]
0.532
[4]
1.429
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[0]
FAB category
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0.395
[2]
1.071
[3]
0.914
[4]
1.256
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[0]
Karyotype type
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0.031
[2]
1.734
[3]
1.142
[4]
2.963
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[0]
IDH1 mutation
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0.287
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0.721
[3]
0.395
[4]
1.317
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1.759
[3]
1.022
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0.879
[2]
1.08
[3]
0.404
[4]
2.883
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0.454
[2]
0.82
[3]
0.488
[4]
1.378
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[0]
6 IRG score
[1]
0.003
[2]
2.097
[3]
1.277
[4]
3.444
locator
section[15]/table-wrap[2]#T3
gaps array · 2 items
[0]
asset:data:geo:GSE37642 not downloaded
[1]
asset:data:geo:GSE37642 licence not read
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method-1
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survival_analysis
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kaplan_meier
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time_to_event_with_censoring
evidence object · 3 fields
score
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verbatim
quote
The Kaplan-Meier curve was used to show differences in OS between the high-risk group and low-risk group patients, based on the IRG signature.
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survival_analysis
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time_to_event_with_censoring
evidence object · 3 fields
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Cox regression
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method-3
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network_analysis
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build_graph
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pathway_enrich
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edge_list
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pathway enrichment
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diagnostic_evaluation
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reference_standard_and_test
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contingency_analysis
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candidate
Automated Assays Laravel application and simulated adapters
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survival_km
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier.
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The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
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GSE37642
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GSE37642
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[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .
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The paper names GSE37642 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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minimax
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were most enriched in immune system process, apoptosis and programmed cell death. In terms of cellu
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The Kaplan-Meier curve was used to show differences in OS between the high-risk group and low-risk group patients, based on the IRG signature.
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Immune disorders in AML and impaired immune cell function have been found to be associated with abnormal karyotypes in AML patients. Immunotherapy has become an alternative therapeutic method that can improve the outcomes of AML patients. For solid tumors, the expression patterns of genes associated with the immune microenvironment provide valuable prognostic information. However, the prognostic roles of immune genes in AML have not been studied as yet. In this study, we identified 136 immune-related genes associated with overall survival in AML patients through a univariate Cox regression analysis using data from TCGA-AML and GTEx datasets. Next, we selected 24 hub genes from among the 136 genes based on the PPI network analysis. The 24 immune-related hub genes further underwent multivariate Cox regression analysis and LASSO regression analysis. Finally, a 6 immune-related gene signature was constructed to predict the prognosis of AML patients. The function of the hub IRGs and the relationships between hub IRGs and transcriptional factors were investigated. We found that higher levels of expression of CSK, MMP7, PSMA7, PDCD1, IKBKG, and ISG15 were associated with an unfavorable prognosis of AML patients. Meanwhile, patients in the TCGA-AML datasets were divided into a high risk score group and a low risk score group, based on the median risk score value. Patients in the high risk group tended to show poorer prognosis [P = 0.00019, HR = 1.89 (1.26-2.83)]. The area under the curve (AUC) was 0.6643. Multivariate Cox Regression assay confirmed that the 6 IRG signature was an independent prognostic factor for AML. The prognostic role of the immune related-gene signature was further validated using an independent AML dataset, GSE37642. In addition, patients in the high risk score group in the TCGA dataset were found to be of an advanced age, IDH mutation, and M5 FAB category. 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"caption": "Clinical characteristics of patients in TCGA-LAML dataset.", "rows": [["Discrete variables", "Number", "Percentage (%)"], ["Gender"], ["Male", "78", "54.55"], ["Female", "65", "45.45"], ["FAB subtype"], ["M0", "15", "10.49"], ["M1", "36", "25.17"], ["M2", "35", "24.48"], ["M4", "34", "23.78"], ["M5", "18", "12.59"], ["M6", "2", "1.4"], ["M7", "3", "2.1"], ["Karyotype"], ["Favorable", "17", "11.89"], ["Intermediate", "94", "65.73"], ["Poor", "30", "20.98"], ["Unknown", "2", "1.4"], ["Living status", "", ""], ["Dead", "97", "67.83"], ["Alive", "46", "32.17"], ["IDH mutation"], ["Positive", "27", "18.88"], ["Negative", "114", "79.72"], ["Unknown", "2", "1.4"], ["FLT3 mutation"], ["Positive", "35", "24.48"], ["Negative", "101", "70.63"], ["Unknown", "7", "4.9"], ["RAS mutation", "", ""], ["Positive", "8", "5.59"], ["Negative", "132", "92.31"], ["Unknown", "3", "2.1"], ["NPM1 mutation"], ["Positive", "42", "29.37"], ["Negative", "98", "68.53"], ["Unknown", "3", ""], ["Continuous Variables", "Range", "Median"], ["Age (years)", "18–88", "60"], ["Overall survival (days)", "0–2861", "334"], ["WBC (10^9/L)", "1–297", "18"]], "row_count": 40, "column_count": 3, "numeric_cells": 60, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33330048:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:922cfa666c0cdf03563a2be5f19be82600178006b25faebf15a242e9afffe7f8", "bytes": 572, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T2", "version": null, "note": "Clinical variables in patients of GSE37642.", "structure": {"pmcid": "PMC7714942", "section_index": 15, "section_title": "Prognostic Signature Construction Using Hub IRGs", "row_count": 15, "column_count": 3}, "table": {"label": "Table 2", "caption": "Clinical variables in patients of GSE37642.", "rows": [["Discrete Variables", "Number", "Percentage (%)"], ["FAB subtype"], ["M0", "8", "6.25"], ["M1", "29", "22.66"], ["M2", "47", "36.72"], ["M4", "17", "13.28"], ["M5", "19", "14.84"], ["M6", "7", "5.47"], ["M7", "1", "0.78"], ["Living Status"], ["Dead", "95", "74.22"], ["Alive", "33", "25.78"], ["Continuous Variables", "Range", "Median"], ["Age (years)", "18–85", "60"], ["Overall Survival (days)", "2–3919", "402"]], "row_count": 15, "column_count": 3, "numeric_cells": 22, "header_rows": 1, "locator": "section[15]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:33330048:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b17de7c68b2db7539b5c674a28ab3ff60069feb30dd5bcc59475b8b8cd33cb41", "bytes": 791, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[2]#T3", "version": null, "note": "Multivariate Cox Regression assay for OS using known clinical prognosticators and 6 IRG risk score.", "structure": {"pmcid": "PMC7714942", "section_index": 15, "section_title": "Prognostic Signature Construction Using Hub IRGs", "row_count": 12, "column_count": 5}, "table": {"label": "Table 3", "caption": "Multivariate Cox Regression assay for OS using known clinical prognosticators and 6 IRG risk score.", "rows": [["", "", "", "95% Exp(B) CI"], ["Variable", "P-value", "Exp(B)", "Lower", "Upper"], ["Age", "0.001", "3.428", "2.061", "5.701"], ["Gender", "0.646", "0.892", "0.548", "1.452"], ["WBC", "0.587", "0.872", "0.532", "1.429"], ["FAB category", "0.395", "1.071", "0.914", "1.256"], ["Karyotype type", "0.031", "1.734", "1.142", "2.963"], ["IDH1 mutation", "0.287", "0.721", "0.395", "1.317"], ["FLT3 mutation", "0.041", "1.759", "1.022", "3.026"], ["RAS mutation", "0.879", "1.08", "0.404", "2.883"], ["NPM1 mutation", "0.454", "0.82", "0.488", "1.378"], ["6 IRG score", "0.003", "2.097", "1.277", "3.444"]], "row_count": 12, "column_count": 5, "numeric_cells": 42, 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