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Lung adenocarcinoma is one of the deadliest tumors. Studies have shown that N6-methyladenosine RNA methylation regulators, as a dynamic chemical modification, affect the occurrence and development of lung adenocarcinoma. To investigate the relationship between mutations and expression levels of m6A regulators in lung adenocarcinoma, we investigated the mutations and expression levels of 38 m6A regulators. We found that mutations in m6A regulatory factors did not affect the changes in expression levels, and 19 differentially expressed genes were identified. All tumor samples were classified into two subtypes based on the expression levels of 19 differentially expressed m6A-regulated genes. Survival analysis showed significant differences in survival between the two subtypes. To explore the relationship between immune cell infiltration and survival in both subtypes, we calculated the infiltration of 23 immune cells in both subtypes, and we found that the subtype with high immune cell infiltration had better survival. We found that subtypes with low tumor purity and high stromal and immune scores had better survival. The m6A-related immune genes were identified by taking the intersection of differentially expressed genes and immune genes in the two isoforms and calculating the Pearson correlation coefficients between the intersecting immune genes and the differentially expressed m6A-regulated genes. Finally, a prognostic model associated with m6A and associated with immunity was developed using prognostic genes screened from m6A-associated immune genes. The predictive power of the model was evaluated and our model was able to achieve good prediction.
Altorki NK, Markowitz GJ, Gao D, Port JL, Saxena A, Stiles B, McGraw T, Mittal V (2019) The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer 19: 9−31
Baghban R, Roshangar L, Jahanban-Esfahlan R, Seidi K, Ebrahimi-Kalan A, Jaymand M, Kolahian S, Javaheri T, Zare P (2020) Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal 18: 59. https://doi.org/10.1186/s12964-020-0530-4
Bai H, Li QZ, Qi YC, Zhai YY, Jin W (2022) The prediction of tumor and normal tissues based on the DNA methylation values of ten key sites. Biochim Biophys Acta Gene Regul Mech 1865: 194841. https://doi.org/10.1016/j.bbagrm.2022.194841
Barbieri I, Kouzarides T (2020) Role of RNA modifications in cancer. Nat Rev Cancer 20: 303−322
Chen J, Gao G, Li L, Ding J, Chen X, Lei J, Long H, Wu L, Long X, He L, Shen Y, Yang J, Lu Y, Sun Y (2022) Pan-cancer study of SHC-adaptor protein 1 (SHC1) as a diagnostic, prognostic and immunological biomarker in human cancer. Front Genet 13: 817118. https://doi.org/10.3389/fgene.2022.817118
Denisenko TV, Budkevich IN, Zhivotovsky B (2018) Cell death-based treatment of lung adenocarcinoma. Cell Death Dis 9: 117. https://doi.org/10.1038/s41419-017-0063-y
Ding Y, Qi N, Wang K, Huang Y, Liao J, Wang H, Tan A, Liu L, Zhang Z, Li J, Kong J, Qin S, Jiang Y (2020) FTO facilitates lung adenocarcinoma cell progression by activating cell migration through mRNA demethylation. Onco Targets Ther 13: 1461−1470
Do HTT, Lee CH, Cho J (2020) Chemokines and their receptors: multifaceted roles in cancer progression and potential value as cancer prognostic markers. Cancers (Basel) 12: 287. https://doi.org/10.3390/cancers12020287
Dolly SO, Collins DC, Sundar R, Popat S, Yap TA (2017) Advances in the development of molecularly targeted agents in non-small-cell lung cancer. Drugs 77(8): 813−827
Fatai AA, Gamieldien J (2018) A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer. BMC Cancer 18: 377. https://doi.org/10.1186/s12885-018-4103-5
Feng ZX, Li QZ, Meng JJ (2019) Modeling the relationship of diverse genomic signatures to gene expression levels with the regulation of long-range enhancer-promoter interactions. Biophysics Reports 5: 123−132
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoué F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pagès F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313: 1960−1964
Galon J, Fridman WH, Pagès F (2007) The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res 67: 1883−1886
Guo X, Liu Y, Liu LJ, Li J, Zhao L, Jin XR, Yan W, Lin BQ, Shi S, Li ZY, Wang S, Wu X, Chen HY, Shen Y, Wei YW (2021) Development and validation of survival nomograms in colorectal cancer patients with synchronous liver metastases underwent simultaneous surgical treatment of primary and metastatic lesions. Am J Cancer Res 11: 2654−2669
Hanahan D, Coussens LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21: 309−322
Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Jr., Wu YL, Paz-Ares L (2017) Lung cancer: current therapies and new targeted treatments. Lancet 389: 299−311
Hu M, Polyak K (2008) Microenvironmental regulation of cancer development. Curr Opin Genet Dev 18: 27−34
Khan RIN, Malla WA (2021) m(6)A modification of RNA and its role in cancer, with a special focus on lung cancer. Genomics 113: 2860−2869
Kobayashi M, Nagashio R, Saito K, Aguilar-Bonavides C, Ryuge S, Katono K, Igawa S, Tsuchiya B, Jiang SX, Ichinoe M, Murakumo Y, Saegusa M, Satoh Y, Sato Y (2018) Prognostic significance of S100A16 subcellular localization in lung adenocarcinoma. Hum Pathol 74: 148−155
Li M, Zha X, Wang S (2021) The role of N6-methyladenosine mRNA in the tumor microenvironment. Biochim Biophys Acta Rev Cancer 1875: 188522. https://doi.org/10.1016/j.bbcan.2021
Ma L, Chen T, Zhang X, Miao Y, Tian X, Yu K, Xu X, Niu Y, Guo S, Zhang C, Qiu S, Qiao Y, Fang W, Du L, Yu Y, Wang J (2021) The m(6)A reader YTHDC2 inhibits lung adenocarcinoma tumorigenesis by suppressing SLC7A11-dependent antioxidant function. Redox Biol 38: 101801. https://doi.org/10.1016/j.redox.2020.101801
Pagès F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353: 2654−2666
Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19: 1423−1437
Shulman Z, Stern-Ginossar N (2020) The RNA modification N(6)-methyladenosine as a novel regulator of the immune system. Nat Immunol 21: 501−512
Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72: 7−33
Song P, Zhao F, Li D, Qu J, Yao M, Su Y, Wang H, Zhou M, Wang Y, Gao Y, Li F, Zhao D, Zhang F, Rao Y, Xia M, Li H, Wang J, Cheng M (2022) Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells. Acta Pharm Sin B 12: 2905−2922
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102: 15545−15550
Sun T, Wu R, Ming L (2019) The role of m6A RNA methylation in cancer. Biomed Pharmacother 112: 108613. https://doi.org/10.1016/j.biopha.2019
Xu Y, Lv D, Yan C, Su H, Zhang X, Shi Y, Ying K (2022) METTL3 promotes lung adenocarcinoma tumor growth and inhibits ferroptosis by stabilizing SLC7A11 m(6)A modification. Cancer Cell Int 22: 11. https://doi.org/10.1186/s12935-021-02433-6
Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, Treviño V, Shen H, Laird PW, Levine DA, Carter SL, Getz G, Stemke-Hale K, Mills GB, Verhaak RG (2013) Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun 4: 2612. https://doi.org/10.1038/ncomms3612
Zaccara S, Ries RJ, Jaffrey SR (2019) Reading, writing and erasing mRNA methylation. Nat Rev Mol Cell Biol 20: 608−624
Zhang B, Wu Q, Li B, Wang D, Wang L, Zhou YL (2020a) m(6)A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer. Mol Cancer 19: 53. https://doi.org/10.1186/s12943-020-01170-0
Zhang Q, Wang W, Zhou Q, Chen C, Yuan W, Liu J, Li X, Sun Z (2020b) Roles of circRNAs in the tumour microenvironment. Mol Cancer 19: 14. https://doi.org/10.1186/s12943-019-1125-9
Zhang Z, Zhang C, Luo Y, Wu P, Zhang G, Zeng Q, Wang L, Yang Z, Xue L, Zheng B, Zeng H, Tan F, Xue Q, Gao S, Sun N, He J (2021) m(6)A regulator expression profile predicts the prognosis, benefit of adjuvant chemotherapy, and response to anti-PD-1 immunotherapy in patients with small-cell lung cancer. BMC Med 19: 284. https://doi.org/10.1186/s12916-021-02148-5
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