Identification of m6A-related lncRNAs as prognostic signature within colon tumor immune microenvironment

被引:5
作者
Cao, Lichao [1 ,2 ]
Zhang, Shenrui [3 ]
Ba, Ying [3 ]
Zhang, Hezi [3 ,4 ]
机构
[1] Northwest Univ, Prov Key Lab Biotechnol Shaanxi Prov, Xian, Peoples R China
[2] Northwest Univ, Sch Life Sci, Key Lab Resource Biol & Biotechnol Western China, Minist Educ, Xian, Peoples R China
[3] Shenzhen Nucleus Gene Technol Co Ltd, Res & Dev Dept, Shenzhen, Peoples R China
[4] Shenzhen Nucl Gene Technol Co Ltd, Shenzhen, Peoples R China
关键词
colon cancer; lncRNAs; N6-methylandenosine; prognostic model; tumor immune microenvironment; CANCER;
D O I
10.1002/cnr2.1828
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The current study probed prognosis-related potential for m6A-related lncRNAs signatures within colon tumor immune microenvironment (TIM). MethodsAfter downloading transcriptomic datasets for colon cancer (CC) patients from The Cancer Genome Atlas (TCGA), they were divided, in a 1:1 ratio, within training or test datasets. m6A-related lncRNAs were then scrutinized across such dataset using Pearson correlation assessment before generating a m6A-related lncRNAs prognosis-related model using the training dataset. The latter was then validated with the test and the whole dataset. In addition, we compared the differences of TIM and the estimated IC50 of drug response between the high- and low-risk groups. Results: Overall survival (OS) resulted as linked with 11 m6A-related lncRNAs, while within the developed prognosis-related model, areas-under-curves were as follows: within training dataset, values at 3-, 4-, and 5-years were 0.777, 0.819, and 0.805, accordingly, and for test one, they were 0.697, 0.682, and 0.706, respectively. Finally, the values for the whole dataset were 0.675 (3-year), 0.682 (4-years), and 0.679 (5-years), accordingly. Moreover, CC cases categorized within low-risk cohort demonstrated enhanced OS (p < .0001), lower metastasis (p = 2e-06) and lower T stage (p = .0067), more instability for microsatellite status (p = .012), and downregulation for PD-L1, PD-1, CTLA-4, LAG3, and HAVCR2 (p < .05). In addition, risk scorings were significantly linked to the degree of infiltrative intensity for CD8 and CD4 (memory resting) T-cells, T-regulatory (Tregs), and Mast cells triggering (p < .05). Patients with low infiltrative propensity for CD4 T-cells also had better OS (p = .016). Moreover, six representative drugs were found to be sensitive for treating CC patients. Conclusion: A robust m6A-related prognostic model with great performances was developed before exploring the TIM characteristics and its potential therapeutic drugs, which might improve the prognosis and therapeutic efficacy.
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页数:14
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共 26 条
[1]   Tim-3 finds its place in the cancer immunotherapy landscape [J].
Acharya, Nandini ;
Sabatos-Peyton, Catherine ;
Anderson, Ana Carrizosa .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (01)
[2]   The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging [J].
Amin, Mahul B. ;
Greene, Frederick L. ;
Edge, Stephen B. ;
Compton, Carolyn C. ;
Gershenwald, Jeffrey E. ;
Brookland, Robert K. ;
Meyer, Laura ;
Gress, Donna M. ;
Byrd, David R. ;
Winchester, David P. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2017, 67 (02) :93-99
[3]   Long Noncoding RNA and Cancer: A New Paradigm [J].
Bhan, Arunoday ;
Soleimani, Milad ;
Mandal, Subhrangsu S. .
CANCER RESEARCH, 2017, 77 (15) :3965-3981
[4]   Understanding the tumor immune microenvironment (TIME) for effective therapy [J].
Binnewies, Mikhail ;
Roberts, Edward W. ;
Kersten, Kelly ;
Chan, Vincent ;
Fearon, Douglas F. ;
Merad, Miriam ;
Coussens, Lisa M. ;
Gabrilovich, Dmitry I. ;
Ostrand-Rosenberg, Suzanne ;
Hedrick, Catherine C. ;
Vonderheide, Robert H. ;
Pittet, Mikael J. ;
Jain, Rakesh K. ;
Zou, Weiping ;
Howcroft, T. Kevin ;
Woodhouse, Elisa C. ;
Weinberg, Robert A. ;
Krummel, Matthew F. .
NATURE MEDICINE, 2018, 24 (05) :541-550
[5]   Long noncoding RNAs: functions and mechanisms in colon cancer [J].
Chen, Sian ;
Shen, Xian .
MOLECULAR CANCER, 2020, 19 (01)
[6]   The role of m6A RNA methylation in human cancer [J].
Chen, Xiao-Yu ;
Zhang, Jing ;
Zhu, Jin-Shui .
MOLECULAR CANCER, 2019, 18 (1)
[7]   m6A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer [J].
Chong, Wei ;
Shang, Liang ;
Liu, Jin ;
Fang, Zhen ;
Du, Fengying ;
Wu, Hao ;
Liu, Yang ;
Wang, Zhe ;
Chen, Yang ;
Jia, Shengtao ;
Chen, Liming ;
Li, Leping ;
Chen, Hao .
THERANOSTICS, 2021, 11 (05) :2201-2217
[8]   N6-methyladenosine links RNA metabolism to cancer progression [J].
Dai, Dongjun ;
Wang, Hanying ;
Zhu, Liyuan ;
Jin, Hongchuan ;
Wang, Xian .
CELL DEATH & DISEASE, 2018, 9
[9]   Colorectal cancer [J].
Dekker, Evelien ;
Tanis, Pieter J. ;
Vleugels, Jasper L. A. ;
Kasi, Pashtoon M. ;
Wallace, Michael B. .
LANCET, 2019, 394 (10207) :1467-1480
[10]   Functions of N6-methyladenosine and its role in cancer [J].
He, Liuer ;
Li, Huiyu ;
Wu, Anqi ;
Peng, Yulong ;
Shu, Guang ;
Yin, Gang .
MOLECULAR CANCER, 2019, 18 (01)