Comprehensive analysis of m6A regulators prognostic value in prostate cancer - PubMed Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul 25;12(14):14863-14884.
doi: 10.18632/aging.103549. Epub 2020 Jul 25.

Comprehensive analysis of m6A regulators prognostic value in prostate cancer

Guangjie Ji  1 , Cong Huang  1 , Shiming He  1 , Yanqing Gong  1 , Gang Song  1 , Xuesong Li  1 , Liqun Zhou  1
Affiliations

Comprehensive analysis of m6A regulators prognostic value in prostate cancer

Guangjie Ji et al. Aging (Albany NY). .

Abstract

Background: N6-methyladenosine (m6A) is the most prevalent RNA modification. While the role of m6A in prostate cancer remains unknown. We aim to measure the effects of m6A methylation regulatory genes during the development and progression of prostate cancer.

Methods: We collected transcriptome information and gene-level alteration data from The Cancer Genome Atlas datasets. The log-rank test and Cox regression model were used to examine the prognosis value of m6A methylation regulatory genes of prostate cancer.

Results: We discovered that most of m6A methylation regulators were highly expressed in aggressive prostate cancer. Univariable and multivariable Cox regression results showed that the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) and N6-adenosine-methyltransferase non-catalytic subunit (METTL14) and copy number variant of AlkB Homolog 5 (ALKBH5) were considerably associated with a recurrence-free survival of prostate cancer. Furthermore, a high level of m6A methylation in mRNA promotes the progression of prostate cancer via regulating subcellular protein localization.

Conclusion: Patients with a high level of mRNA methylation resulted from overexpression of reader proteins and methyltransferase complexes had poor survival benefits through influencing protein subcellular location in prostate cancer.

Keywords: N6-methyladenosine; RNA modification; copy number variants; prostate cancer.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that there are no conflicts of interest concerning this article.

Figures

Figure 1
Figure 1
The mRNA expression of m6A methylation regulators in normal versus tumor samples of prostate cancer respectively. (A) YTHDC2; (B) YTHDF1; (C) IGF2BP2; (D) HNRNPC; (E) METTL3; (F) METTL14; (G) RBM15; (H) HNRNPA2B1; (I) RBM15B; (J) WTAP; (K) VIRMA; (L) ZC3H13; (M) FTO; (N) ALKBH5
Figure 2
Figure 2
The mRNA expression of m6A methylation regulators in paired normal and primary prostate cancer samples.
Figure 3
Figure 3
Association between mRNA expression of m6A methylation regulators and Gleason Score of prostate cancer.(A) YTHDC1; (B) IGF2BP2; (C) IGF2BP3; (D) HNRNPA2B1; (E) METTL3; (F) RBM15B; (G) WTAP; (H) VIRMA; (I) ALKBH5.
Figure 4
Figure 4
Survival analysis of expression of m6A methylation regulators. (A–C) Univariable cox regression analysis of there m6a methylation regulators with the significant p-value. (D) Multivariable cox regression analysis of all m6a methylation regulators.
Figure 5
Figure 5
Survival analysis of expression of m6A methylation regulators. (A) correlation between expression of HNRNPA2B1 and GS; (B) Univariable cox regression analysis of HNRNPA2B1; (C) Multivariable cox regression analysis of all m6a methylation regulators.
Figure 6
Figure 6
CNV distribution and protein level of m6A methylation regulatory genes in TCGA-PRAD. (A) distribution of different CNV patterns; (B, C) Immunohistochemistry images of m6A regulators from the human protein atlas database.
Figure 7
Figure 7
Association between mRNA expression and different CNV patterns of m6A methylation regulators. (A) YTHDC1; (B) YTHDC2; (C) YTHDF1; (D) YTHDF3; (E) IGF2BP2; (F) IGF2BP3; (G) HNRNPA2B1; (H) METTL3; (I) METTL14; (J) RBM15; (K) RBM15B; (L) WTAP; (M) ZC3H13; (N) ALKBH5; (O) FTO. Amplification: low-level amplification and high-level amplification. CNV loss: homozygous deletion and single-copy deletion.
Figure 8
Figure 8
Survival analysis of CNVs of m6a methylation regulators. (A–F) Univariable cox regression analysis of there m6a methylation regulators with the significant p-value. (G) Multivariable cox regression analysis of all m6a methylation regulators.
Figure 9
Figure 9
Analysis of the pathway regulated by m6A methylation. (A) ROC of all methylation regulators model. (B) GO analysis of differentiated genes between high risk of m6A methylation group and its low-risk group. ROC: Receiver Operating Characteristic; GO: gene ontology.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136:E359–86. 10.1002/ijc.29210 - DOI - PubMed
    1. Royce TJ, Chen MH, Wu J, Loffredo M, Renshaw AA, Kantoff PW, D’Amico AV. Surrogate end points for all-cause mortality in men with localized unfavorable-risk prostate cancer treated with radiation therapy vs radiation therapy plus androgen deprivation therapy: a secondary analysis of a randomized clinical trial. JAMA Oncol. 2017; 3:652–58. 10.1001/jamaoncol.2016.5983 - DOI - PMC - PubMed
    1. Freiberger C, Berneking V, Vögeli TA, Kirschner-Hermanns R, Eble MJ, Pinkawa M. Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival. Radiat Oncol. 2017; 12:98. 10.1186/s13014-017-0837-5 - DOI - PMC - PubMed
    1. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, Lotan TL, Zheng Q, de Marzo AM, et al.. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014; 371:1028–38. 10.1056/NEJMoa1315815 - DOI - PMC - PubMed
    1. Boccaletto P, Machnicka MA, Purta E, Piatkowski P, Baginski B, Wirecki TK, de Crécy-Lagard V, Ross R, Limbach PA, Kotter A, Helm M, Bujnicki JM. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 2018; 46:D303–07. 10.1093/nar/gkx1030 - DOI - PMC - PubMed

Publication types

MeSH terms

Substances