Objective: The expression levels and clinical significance of YTHDF1 and YTHDF2 in lung squamous cell carcinoma (LUSC) tissues were analyzed using bioinformatics and immunohistochemical methods. Methods: TCGA database was used to analyze the expression and correlation of MYC and FTO in colorectal cancer.Gene set enrichment analysis (GSEA) revealed the biological functions and signaling pathways associated with YTHDF1 and YTHDF2.Finally,the expression of YTHDF1 and YTHDF2 in LUSC tissues was validated through immunohistochemical experiments,and the correlation between expression levels of YTHDF1 and YTHDF2 and clinical features was analyzed.In addition,we investigated the relation between expression levels of YTHDF1 and YTHDF2 and PD-L1 by statistical methods. Results: (1) YTHDF1 and YTHDF2 were higher in tumors than in adjacent tissues(P＜0.05);(2) YTHDF1 was correlated with T stage and tumor clinical stage(P＜0.05);(3) Age was an independent risk factor for overall survival (OS) of LUSC patients, and YTHDF1 expression and T stage were independent risk factors for disease specific survival (DSS);(4)Genes in the groups with high expression of YTHDF1 and YTHDF2 were mainly enriched in therapeutic targets.Low expression groups of YTHDF1 and YTHDF2 were related to immune activity.(5)YTHDF2 were positively correlated with the expression of PD-L1(P＜0.05). Conclusion: The expression levels of YTHDF1 and YTHDF2 may affect the immune microenvironment of LUSC, revealing its potential as targets and biological markers for immunotherapy.
BAI Tianjing
,
CAI Liting
,
YAN Pufangxin
,
WANG Fengyun
. Expression of YTHDF1 and YTHDF2 in lung squamous cell carcinoma and their correlation with PD-L1[J]. Journal of Baotou Medical College, 2025
, 41(11)
: 29
-35
.
DOI: 10.16833/j.cnki.jbmc.2025.11.006
[1] Braf F, Laversane M, Sung H, et al.Global cancer statistics 2022: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin, 2024, 74(3): 229-263.
[2] 赵文静, 尹周一, 王裕新, 等.2024美国癌症统计报告解读及中美癌症流行情况对比[J].肿瘤防治研究, 2024, 51(8): 630-641.
[3] Liang Y, Wang N, Zhang Y, et al.Self-restricted circular RNA circSOX2 suppressed the malignant progression in SOX2-amplified LUSC[J].Cell Death Dis, 2022, 13(10): 873.
[4] Bonomi PD, Gandara D, Hirsch FR, et al.Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer[J].Ann Oncol, 2018, 29(8): 1701-1709.
[5] Liu ZX, Li LM, Sun HL,et al.Link Between m6A Modification and Cancers[J].Front Bioeng Biotechnol, 2018, 6: 89.
[6] Bao Y, Zhai J, Chen H, et al.Targeting m6A reader YTHDF1 augments antitumour immunity and boosts anti-PD-1 efficacy in colorectal cancer[J].Gut, 2023, 72(8): 1497-1509.
[7] Ren W, Yuan Y, Li Y, et al.The function and clinical implication of YTHDF1 in the human system development and cancer[J].Biomark Res, 2023, 11(1): 5.
[8] Liu T, Wei Q, Jin J, et al.The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation[J].Nucleic Acids Res, 2020, 48(7): 3816-3831.
[9] Li W, Chen G, Feng Z, et al.YTHDF1 promotes the proliferation, migration, and invasion of prostate cancer cells by regulating TRIM44[J].Genes Genomics, 2021, 43(12): 1413-1421.
[10] Chen X, Zhou X, Wang X.m(6)A binding protein YTHDF2 in cancer[J].Exp Hematol Oncol, 2022, 11(1): 21.
[11] Yang J, Chen Y, He Y, et al.YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance[J].Drug Dev Res, 2024, 85(2): e22179.
[12] Jiang X, Chen X, Huang X, et al.DNA methylation-regulated YTHDF2 correlates with cell migration and immune cell infiltration in glioma[J].Aging, 2022, 14(19): 7774-7793.
[13] Tsuchyia K, Yoshimura K, Inoue Y, et al.YTHDF1 and YTHDF2 are associated with better patient survival and an inflamed tumor-immune microenvironment in non-small-cell lung cancer[J].Oncoimmunology, 2021, 10(1): 1962656.
[14] Liu X, Liu L, Dong Z, et al.Expression patterns and prognostic value of m(6)A-related genes in colorectal cancer[J].Am J Transl Res, 2019, 11(7): 3972-3991.
[15] Xu P, Hu K, Zhang P, et al.Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis[J].Cancer Cell Int, 2022, 22(1): 13.
[16] Wu T, Dai Y.Tumor microenvironment and therapeutic response[J].Cancer Lett, 2017, 387: 61-68.
[17] Bai X, Wong CC, Pan Y, et al.Loss of YTHDF1 in gastric tumors restores sensitivity to antitumor immunity by recruiting mature dendritic cells[J].J Immunother Cancer, 2022, 10(2): e003663.
[18] Zhang L, Dou X, Zheng Z, et al.YTHDF2/m(6) A/NF-κB axis controls anti-tumor immunity by regulating intratumoral Tregs[J].EMBO J, 2023, 42(15): e113126.
[19] Ma S, Yan J, Barr T, et al.The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity[J].J Exp Med, 2021, 218(8): e20210279.
