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pmid:39292326

Characterizing m6A modification factors and their interactions in colorectal cancer: implications for tumor subtypes and clinical outcomes.

Weidong Sun · Yingchao Su · Zhiqiang Zhang

Discover oncology · 2024 doi:10.1007/s12672-024-01298-1

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title
Characterizing m6A modification factors and their interactions in colorectal cancer: implications for tumor subtypes and clinical outcomes.
doi
10.1007/s12672-024-01298-1
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39292326
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Weidong Sun
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Yingchao Su
[2]
Zhiqiang Zhang
journal
Discover oncology
year
2024
abstract
BACKGROUND: The study aims to comprehensively combine colorectal cancer data cohorts in order to analyze the effects of various DNA methylation-coding genes on colorectal cancer patients. The annual incidence and mortality of colorectal cancer are very high, and there are no effective treatments for advanced colorectal cancer. DNA methylation is a method widely used to regulate epigenetics in the molecular mechanism study of tumors. METHOD: Three single-cell cohorts GSE166555, GSE146771, and EMTAB8107, and five transcriptome cohorts GSE17536, GSE39582, GSE72970, and TCGA-CRC (TCGA-COAD and TCGA-READ) were applied in this study. 2 erasers (ALKBH5 and FTO), There are 7 writers (METTL3, METTL14, WTAP, VIRMA, RBM15, RBM15B, and ZC3H13) and 11 readers (YTHDC1, IGF2BP1, IGF2BP2, IGF2BP3, YTHDF1, YTHDF3, YTHDC2, and HNRNPA2B1, YTHDF2, HNRNPC and RBMX), a total of 20 M6A regulators, were used as the basis of the dataset in this study and were applied to the construction of molecular typing and prognostic models. Drugs that are differentially sensitive in methylation-regulated gene-related prognostic models were identified using the ConsensusClusterPlus package, which was also used to identify distinct methylation regulatory expression patterns in colorectal cancer and to model the relationship between tissue gene expression profiles and drug IC50 values. Finally, TISCH2 assessed which immune cells were significantly expressed with M6A scores. The immunosuppression of M6A methylation is spatially explained. RESULTS: This study used data from 583 CRC patients in the TCGA-CRC cohort. Firstly, the mutation frequency and CNV variation frequency of 20 m6A modification-related factors were analyzed, and the corresponding histogram and heat map were drawn. The study next analyzed the expression variations between mutant and wild forms of the VIRMA gene and explored differences in the expression of these variables in tumor and normal tissues. In addition, the samples were divided into different subgroups by molecular clustering method based on m6A modification, and each subgroup's expression and clinicopathological characteristics were analyzed. Finally, we compared prognostic differences, tumor microenvironment (TME) characteristics, immune cell infiltration, and gene function enrichment among different subpopulations. We also developed a colorectal cancer m6A-associated gene signature and validated its prognostic effects across multiple cohorts. Finally, using single-cell RNA sequencing data, we confirmed that tumor cells show elevated expression of m6A-related gene signatures. DISCUSSION: This study explored the mutation frequency, expression differences, interactions, molecular clustering, prognostic effect, and association with tumor characteristics of m6A modification-related factors in CRC and validated them at the single-cell level. These results clarify the association between m6A alteration and colorectal cancer (CRC) and offer important insights into the molecular recognition and management of cancer.
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Using LASSO + multivariate Cox regression analysis, we generated a m6A-related signature and the m6A score based on the prognostic DEGs between the two m6A gene clusters for each CRC patient (Fig. 6a and b).
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sections[16] "Generation of m6A score" paragraph 2
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Using LASSO + multivariate Cox regression analysis, we generated a m6A-related signature and the m6A score based on the prognostic DEGs between the two m6A gene clusters for each CRC patient (Fig. 6a and b).
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[162]
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[163]
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[167]
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[168]
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[169]
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[170]
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[171]
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[172]
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[173]
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[174]
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[176]
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[177]
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[178]
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[179]
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[180]
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[181]
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[182]
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[183]
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[184]
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[185]
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[186]
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[187]
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[188]
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[189]
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[190]
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[195]
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[197]
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[198]
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[199]
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[200]
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[204]
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[205]
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[206]
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[207]
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[208]
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[209]
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[210]
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[211]
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[212]
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[213]
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[214]
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[216]
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[217]
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[218]
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[219]
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[220]
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[221]
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[222]
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[223]
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[224]
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[225]
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[226]
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[227]
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[228]
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[229]
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[230]
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[231]
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[232]
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[233]
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[234]
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[235]
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[238]
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[239]
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[240]
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[241]
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[242]
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[243]
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[244]
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[246]
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[247]
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[248]
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[249]
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[250]
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[251]
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[252]
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[253]
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[254]
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[255]
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[256]
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[257]
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[258]
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[259]
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[260]
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[261]
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[262]
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[263]
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[264]
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[265]
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[266]
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[267]
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[268]
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[269]
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[270]
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[271]
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[272]
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[273]
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[274]
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[275]
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[276]
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[277]
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[278]
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[279]
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[280]
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[281]
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[282]
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[283]
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[284]
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[285]
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[286]
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[287]
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[288]
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[289]
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[290]
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[291]
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[292]
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[293]
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[294]
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[295]
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[296]
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[297]
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[298]
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[299]
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[300]
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[301]
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[302]
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[303]
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[304]
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[305]
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[306]
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[307]
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[308]
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[309]
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[310]
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[311]
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[312]
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[313]
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[314]
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[315]
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[316]
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[317]
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[318]
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[319]
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[320]
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[321]
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[322]
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[323]
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[324]
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[325]
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[326]
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[327]
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[328]
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[329]
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[330]
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[331]
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[332]
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[333]
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[334]
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[335]
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[336]
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[337]
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[338]
GSM972276
[339]
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[340]
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[341]
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[342]
GSM972280
[343]
GSM972281
[344]
GSM972282
[345]
GSM972283
[346]
GSM972284
[347]
GSM972285
[348]
GSM972286
[349]
GSM972287
[350]
GSM972288
[351]
GSM972289
[352]
GSM972290
[353]
GSM972291
[354]
GSM972292
[355]
GSM972293
[356]
GSM972294
[357]
GSM972295
[358]
GSM972296
[359]
GSM972297
[360]
GSM972298
[361]
GSM972299
[362]
GSM972300
[363]
GSM972301
[364]
GSM972302
[365]
GSM972303
[366]
GSM972304
[367]
GSM972305
[368]
GSM972306
[369]
GSM972307
[370]
GSM972308
[371]
GSM972309
[372]
GSM972310
[373]
GSM972311
[374]
GSM972312
[375]
GSM972313
[376]
GSM972314
[377]
GSM972315
[378]
GSM972316
[379]
GSM972317
[380]
GSM972318
[381]
GSM972319
[382]
GSM972320
[383]
GSM972321
[384]
GSM972322
[385]
GSM972323
[386]
GSM972324
[387]
GSM972325
[388]
GSM972326
[389]
GSM972327
[390]
GSM972328
[391]
GSM972329
[392]
GSM972330
[393]
GSM972331
[394]
GSM972332
[395]
GSM972333
[396]
GSM972334
[397]
GSM972335
[398]
GSM972336
[399]
GSM972337
[400]
GSM972338
[401]
GSM972339
[402]
GSM972340
[403]
GSM972341
[404]
GSM972342
[405]
GSM972343
[406]
GSM972344
[407]
GSM972345
[408]
GSM972346
[409]
GSM972347
[410]
GSM972348
[411]
GSM972349
[412]
GSM972350
[413]
GSM972351
[414]
GSM972352
[415]
GSM972353
[416]
GSM972354
[417]
GSM972355
[418]
GSM972356
[419]
GSM972357
[420]
GSM972358
[421]
GSM972359
[422]
GSM972360
[423]
GSM972361
[424]
GSM972362
[425]
GSM972363
[426]
GSM972364
[427]
GSM972365
[428]
GSM972366
[429]
GSM972367
[430]
GSM972368
[431]
GSM972369
[432]
GSM972370
[433]
GSM972371
[434]
GSM972372
[435]
GSM972373
[436]
GSM972374
[437]
GSM972375
[438]
GSM972376
[439]
GSM972377
[440]
GSM972378
[441]
GSM972379
[442]
GSM972380
[443]
GSM972381
[444]
GSM972382
[445]
GSM972383
[446]
GSM972384
[447]
GSM972385
[448]
GSM972386
[449]
GSM972387
[450]
GSM972388
[451]
GSM972389
[452]
GSM972390
[453]
GSM972391
[454]
GSM972392
[455]
GSM972393
[456]
GSM972394
[457]
GSM972395
[458]
GSM972396
[459]
GSM972397
[460]
GSM972398
[461]
GSM972399
[462]
GSM972400
[463]
GSM972401
[464]
GSM972402
[465]
GSM972403
[466]
GSM972404
[467]
GSM972405
[468]
GSM972406
[469]
GSM972407
[470]
GSM972408
[471]
GSM972409
[472]
GSM972410
[473]
GSM972411
[474]
GSM972412
[475]
GSM972413
[476]
GSM972414
[477]
GSM972415
[478]
GSM972416
[479]
GSM972417
[480]
GSM972418
[481]
GSM972419
[482]
GSM972420
[483]
GSM972421
[484]
GSM972422
[485]
GSM972423
[486]
GSM972424
[487]
GSM972425
[488]
GSM972426
[489]
GSM972427
[490]
GSM972428
[491]
GSM972429
[492]
GSM972430
[493]
GSM972431
[494]
GSM972432
[495]
GSM972433
[496]
GSM972434
[497]
GSM972435
[498]
GSM972436
[499]
GSM972437
[500]
GSM972438
[501]
GSM972439
[502]
GSM972440
[503]
GSM972441
[504]
GSM972442
[505]
GSM972443
[506]
GSM972444
[507]
GSM972445
[508]
GSM972446
[509]
GSM972447
[510]
GSM972448
[511]
GSM972449
[512]
GSM972450
[513]
GSM972451
[514]
GSM972452
[515]
GSM972453
[516]
GSM972454
[517]
GSM972455
[518]
GSM972456
[519]
GSM972457
[520]
GSM972458
[521]
GSM972459
[522]
GSM972460
[523]
GSM972461
[524]
GSM972462
[525]
GSM972463
[526]
GSM972464
[527]
GSM972465
[528]
GSM972466
[529]
GSM972467
[530]
GSM972468
[531]
GSM972469
[532]
GSM972470
[533]
GSM972471
[534]
GSM972472
[535]
GSM972473
[536]
GSM972474
[537]
GSM972475
[538]
GSM972476
[539]
GSM972477
[540]
GSM972478
[541]
GSM972479
[542]
GSM972480
[543]
GSM972481
[544]
GSM972482
[545]
GSM972483
[546]
GSM972484
[547]
GSM972485
[548]
GSM972486
[549]
GSM972487
[550]
GSM972488
[551]
GSM972489
[552]
GSM972490
[553]
GSM972491
[554]
GSM972492
[555]
GSM972493
[556]
GSM972494
[557]
GSM972495
[558]
GSM972496
[559]
GSM972497
[560]
GSM972498
[561]
GSM972499
[562]
GSM972500
[563]
GSM972501
[564]
GSM972502
[565]
GSM972503
[566]
GSM972504
[567]
GSM972505
[568]
GSM972506
[569]
GSM972507
[570]
GSM972508
[571]
GSM972509
[572]
GSM972510
[573]
GSM972511
[574]
GSM972512
[575]
GSM972513
[576]
GSM972514
[577]
GSM972515
[578]
GSM972516
[579]
GSM972517
[580]
GSM972518
[581]
GSM972519
[582]
GSM972520
[583]
GSM972521
[584]
GSM972522
sample_count
585
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[6] object · 15 fields
id
data:geo:GSE72970
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72970
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE72970
version
null
note
The data used in the present study are openly accessible in the GTEx, GEO, and TCGA databases.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The data used in the present study are openly accessible in the GTEx, GEO, and TCGA databases.
access_statement_kind
data_availability_statement
sample_accessions array · 124 items
[0]
GSM1875897
[1]
GSM1875898
[2]
GSM1875899
[3]
GSM1875900
[4]
GSM1875901
[5]
GSM1875902
[6]
GSM1875903
[7]
GSM1875904
[8]
GSM1875905
[9]
GSM1875906
[10]
GSM1875907
[11]
GSM1875908
[12]
GSM1875909
[13]
GSM1875910
[14]
GSM1875911
[15]
GSM1875912
[16]
GSM1875913
[17]
GSM1875914
[18]
GSM1875915
[19]
GSM1875916
[20]
GSM1875917
[21]
GSM1875918
[22]
GSM1875919
[23]
GSM1875920
[24]
GSM1875921
[25]
GSM1875922
[26]
GSM1875923
[27]
GSM1875924
[28]
GSM1875925
[29]
GSM1875926
[30]
GSM1875927
[31]
GSM1875928
[32]
GSM1875929
[33]
GSM1875930
[34]
GSM1875931
[35]
GSM1875932
[36]
GSM1875933
[37]
GSM1875934
[38]
GSM1875935
[39]
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[40]
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[41]
GSM1875938
[42]
GSM1875939
[43]
GSM1875940
[44]
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[45]
GSM1875942
[46]
GSM1875943
[47]
GSM1875944
[48]
GSM1875945
[49]
GSM1875946
[50]
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[51]
GSM1875948
[52]
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[53]
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[54]
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[55]
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[56]
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[57]
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[58]
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[59]
GSM1875956
[60]
GSM1875957
[61]
GSM1875958
[62]
GSM1875959
[63]
GSM1875960
[64]
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[65]
GSM1875962
[66]
GSM1875963
[67]
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[68]
GSM1875965
[69]
GSM1875966
[70]
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[71]
GSM1875968
[72]
GSM1875969
[73]
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[74]
GSM1875971
[75]
GSM1875972
[76]
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[77]
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[78]
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[79]
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[80]
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[81]
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[82]
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[83]
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[84]
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[85]
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[86]
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[87]
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[88]
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[89]
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[90]
GSM1875987
[91]
GSM1875988
[92]
GSM1875989
[93]
GSM1875990
[94]
GSM1875991
[95]
GSM1875992
[96]
GSM1875993
[97]
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[98]
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[99]
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[100]
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[101]
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[102]
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[103]
GSM1876000
[104]
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[105]
GSM1876002
[106]
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[107]
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[108]
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[109]
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[110]
GSM1876007
[111]
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[112]
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[113]
GSM1876010
[114]
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[115]
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[116]
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[117]
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[118]
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[119]
GSM1876016
[120]
GSM1876017
[121]
GSM1876018
[122]
GSM1876019
[123]
GSM1876020
sample_count
124
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Molecular subtypes of metastatic colorectal cancer are predictive of patient response to chemo and targeted therapies
resolution_checked_at
2026-11-01T17:30:42Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 12 items
[0]
asset:data:geo:EMTAB8107 not downloaded
[1]
asset:data:geo:EMTAB8107 licence not read
[2]
asset:data:geo:GSE146771 not downloaded
[3]
asset:data:geo:GSE146771 licence not read
[4]
asset:data:geo:GSE166555 not downloaded
[5]
asset:data:geo:GSE166555 licence not read
[6]
asset:data:geo:GSE17536 not downloaded
[7]
asset:data:geo:GSE17536 licence not read
[8]
asset:data:geo:GSE39582 not downloaded
[9]
asset:data:geo:GSE39582 licence not read
[10]
asset:data:geo:GSE72970 not downloaded
[11]
asset:data:geo:GSE72970 licence not read
analysis object · 4 fields
state
partial
methods array · 3 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
1
band
verbatim
quote
Using LASSO + multivariate Cox regression analysis, we generated a m6A-related signature and the m6A score based on the prognostic DEGs between the two m6A gene clusters for each CRC patient (Fig. 6a and b).
[1] object · 10 fields
id
method-2
family
group_comparison
specific
mann_whitney
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_mann_whitney
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
Mann-Whitney
[2] object · 10 fields
id
method-3
family
contingency_analysis
specific
chi_square
label
Categorical (contingency table) analysis
dsl_operations array · 1 item
[0]
chi_square_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
categorical_cross_tabulation
evidence object · 3 fields
score
0.8
band
high
quote
χ2
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
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Using LASSO + multivariate Cox regression analysis, we generated a m6A-related signature and the m6A score based on the prognostic DEGs between the two m6A gene clusters for each CRC patient (Fig. 6a and b).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39292326", "kind": "science-record", "revision": 3, "content_hash": "sha256:90e5e425666aef7c6664a5af497cb34bdca9622258db42ae44727c33629c7700", "created_at": "2026-11-01T20:29:28Z", "updated_at": "2026-11-01T22:12:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Characterizing m6A modification factors and their interactions in colorectal cancer: implications for tumor subtypes and clinical outcomes.", "doi": "10.1007/s12672-024-01298-1", "pmid": "39292326", "authors": ["Weidong Sun", "Yingchao Su", "Zhiqiang Zhang"], "journal": "Discover oncology", "year": 2024, "abstract": "BACKGROUND: The study aims to comprehensively combine colorectal cancer data cohorts in order to analyze the effects of various DNA methylation-coding genes on colorectal cancer patients. The annual incidence and mortality of colorectal cancer are very high, and there are no effective treatments for advanced colorectal cancer. DNA methylation is a method widely used to regulate epigenetics in the molecular mechanism study of tumors.\nMETHOD: Three single-cell cohorts GSE166555, GSE146771, and EMTAB8107, and five transcriptome cohorts GSE17536, GSE39582, GSE72970, and TCGA-CRC (TCGA-COAD and TCGA-READ) were applied in this study. 2 erasers (ALKBH5 and FTO), There are 7 writers (METTL3, METTL14, WTAP, VIRMA, RBM15, RBM15B, and ZC3H13) and 11 readers (YTHDC1, IGF2BP1, IGF2BP2, IGF2BP3, YTHDF1, YTHDF3, YTHDC2, and HNRNPA2B1, YTHDF2, HNRNPC and RBMX), a total of 20 M6A regulators, were used as the basis of the dataset in this study and were applied to the construction of molecular typing and prognostic models. Drugs that are differentially sensitive in methylation-regulated gene-related prognostic models were identified using the ConsensusClusterPlus package, which was also used to identify distinct methylation regulatory expression patterns in colorectal cancer and to model the relationship between tissue gene expression profiles and drug IC50 values. Finally, TISCH2 assessed which immune cells were significantly expressed with M6A scores. The immunosuppression of M6A methylation is spatially explained.\nRESULTS: This study used data from 583 CRC patients in the TCGA-CRC cohort. Firstly, the mutation frequency and CNV variation frequency of 20 m6A modification-related factors were analyzed, and the corresponding histogram and heat map were drawn. The study next analyzed the expression variations between mutant and wild forms of the VIRMA gene and explored differences in the expression of these variables in tumor and normal tissues. In addition, the samples were divided into different subgroups by molecular clustering method based on m6A modification, and each subgroup's expression and clinicopathological characteristics were analyzed. Finally, we compared prognostic differences, tumor microenvironment (TME) characteristics, immune cell infiltration, and gene function enrichment among different subpopulations. We also developed a colorectal cancer m6A-associated gene signature and validated its prognostic effects across multiple cohorts. Finally, using single-cell RNA sequencing data, we confirmed that tumor cells show elevated expression of m6A-related gene signatures.\nDISCUSSION: This study explored the mutation frequency, expression differences, interactions, molecular clustering, prognostic effect, and association with tumor characteristics of m6A modification-related factors in CRC and validated them at the single-cell level. These results clarify the association between m6A alteration and colorectal cancer (CRC) and offer important insights into the molecular recognition and management of cancer.", "claims": [{"id": "claim-method", "statement": "Using LASSO + multivariate Cox regression analysis, we generated a m6A-related signature and the m6A score based on the prognostic DEGs between the two m6A gene clusters for each CRC patient (Fig. 6a and b).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39292326", "locator": "sections[16] \"Generation of m6A score\" paragraph 2", "quote": "Using LASSO + multivariate Cox regression analysis, we generated a m6A-related signature and the m6A score based on the prognostic DEGs between the two m6A gene clusters for each CRC patient (Fig. 6a and b)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used in the present study are openly accessible in the GTEx, GEO, and TCGA databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39292326", "locator": "sections[25] \"Data availability\" paragraph 2", "quote": "The data used in the present study are openly accessible in the GTEx, GEO, and TCGA databases."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39292326"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Finally, using single-cell RNA sequencing data, we confirmed that tumor cells show ele", "SE166555, GSE146771, and EMTAB8107, and five transcriptome cohorts GSE17536, GSE39582, GSE72970, and TC"], "order_basis": "paper_text_order:612", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ects across multiple cohorts. Finally, using single-cell RNA sequencing data, we confirmed that tumor cells show ele"], "order_basis": "paper_text_order:2585", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Using LASSO + multivariate Cox regression analysis, we generated a m6A-related signature and the m6A score based on the prognostic DEGs between the two m6A gene clusters for each CRC patient (Fig. 6a and b)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}