Objective To explore the relationship between TBX2 gene and head and neck squamous cell carcinoma (HNSCC), and to analyze the value of methylation prognosis.
Methods The UCSC Xena database, Gene Expression Omnibus (GEO) database, Human Protein Atlas (HPA) database and UALCAN database were comprehensively used to explore the expression, DNA methylation and clinical correlation of TBX2 gene, and gene set enrichment analysis (GSEA) method was used to enrich the signaling pathways involved in TBX2 gene in HNSCC.
Results TBX2 gene was highly expressed in patients with HNSCC, and there was no significant difference in overall survival (OS) in patients with HNSCC in TBX2 gene high expression group and low expression group. However, the expression of TBX2 in HNSCC was related to clinical grade and stage. Low methylation levels at certain cg sites of the TBX2 gene were closely associated with poor OS and progression free survival (PFS). The results of GSEA showed that TBX2 gene was mainly involved in calcium signaling pathway, adhesion plaque, proteasome and other pathways.
Conclusion TBX2 gene can be a biomarker for the specific diagnosis and prognosis of HNSCC.
1.Ghafouri-Fard S, Gholipour M, Taheri M, et al. MicroRNA profile in the squamous cell carcinoma: prognostic and diagnostic roles[J]. Heliyon, 2020, 6(11): e05436. DOI: 10.1016/j.heliyon.2020.e05436.
2.Xue M, Shi Q, Zheng L, et al. Gene signatures of m5C regulators may predict prognoses of patients with head and neck squamous cell carcinoma[J]. Am J Transl Res, 2020, 12(10): 6841-6852.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653571/.
3.Puttipanyalears C, Arayataweegool A, Chalertpet K, et al. TRH site-specific methylation in oral and oropharyngeal squamous cell carcinoma[J]. BMC Cancer, 2018, 18(1): 786. DOI: 10.1186/s12885-018-4706-x.
4.Kazim N, Adhikari A, Oh TJ, et al. The transcription elongation factor TCEA3 induces apoptosis in rhabdomyosarcoma[J]. Cell Death Dis, 2020, 11(1): 67. DOI: 10.1038/s41419-020-2258-x.
5.Navarro Gonzalez J, Zweig AS, Speir ML, et al. The UCSC Genome Browser database: 2021 update[J]. Nucleic Acids Res, 2021, 49(D1): D1046-D1057. DOI: 10.1093/nar/gkaa1070.
6.Chicco D. geneExpressionFromGEO: an R package to facilitate data reading from Gene Expression Omnibus (GEO)[J]. Methods Mol Biol, 2022, 2401: 187-194. DOI: 10.1007/978-1-0716-1839-4_12.
7.Digre A, Lindskog C. The Human Protein Atlas-spatial localization of the human proteome in health and disease[J]. Protein Sci, 2021, 30(1): 218-233. DOI: 10.1002/pro.3987.
8.Chandrashekar DS, Karthikeyan SK, Korla PK, et al. UALCAN: an update to the integrated cancer data analysis platform[J]. Neoplasia, 2022, 25: 18-27. DOI: 10.1016/j.neo.2022.01.001.
9.Castanza AS, Recla JM, Eby D, et al. Extending support for mouse data in the Molecular Signatures Database (MSigDB) [J]. Nat Methods, 2023, 20(11): 1619-1620. DOI: 10.1038/s41592-023-02014-7.
10.Huang Y, Li Z, Zhong Q, et al. Association of TBX2 and P21 expression with clinicopathological features and survival of laryngeal squamous cell carcinoma[J]. Int J Clin Exp Med, 2014, 7(12): 5394-5402. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307495/.
11.Qin T, Li S, Henry LE, et al. Whole-genome CpG- resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes[J]. Cancer Res Commun, 2023, 3(8): 1701-1715. DOI: 10.1158/2767-9764.Crc-23-0009.
12.Werbrouck J, De Ruyck K, Duprez F, et al. Single- nucleotide polymorphisms in DNA double-strand break repair genes: association with head and neck cancer and interaction with tobacco use and alcohol consumption[J]. Mutat Res, 2008, 656(1-2): 74-81. DOI: 10.1016/j.mrgentox.2008.07.013.
13.Ivanova T, Churnosova M, Abramova M, et al. Sex- specific features of the correlation between GWAS-noticeable polymorphisms and hypertension in Europeans of Russia[J]. Int J Mol Sci, 2023, 24(9): 7799. DOI: 10.3390/ijms24097799.
14.Nair L, Zhang W, Laffleur B, et al. Mechanism of noncoding RNA-associated N6-methyladenosine recognition by an RNA processing complex during IgH DNA recombination[J]. Mol Cell, 2021, 81(19): 3949-3964. DOI: 10.1016/j.molcel.2021.07.037.
15.Wang K, Wang S, Zhang Y, et al. SNORD88C guided 2'-O-methylation of 28S rRNA regulates SCD1 translation to inhibit autophagy and promote growth and metastasis in non-small cell lung cancer[J]. Cell Death Differ, 2023, 30(2): 341-355. DOI: 10.1038/s41418-022-01087-9.
16.Min KD, Asakura M, Shirai M, et al. ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis[J]. Sci Rep, 2021, 11(1): 23056. DOI: 10.1038/s41598-021-02390-0.
17.Liu X, Miao Z, Wang Z, et al. TBX2 overexpression promotes proliferation and invasion through epithelial- mesenchymal transition and ERK signaling pathway[J]. Exp Ther Med, 2019, 17(1): 723-729. DOI: 10.3892/etm.2018.7028.