Your browser does not support JavaScript!
http://iet.metastore.ingenta.com
1887

access icon free Integrated expression analysis revealed RUNX2 upregulation in lung squamous cell carcinoma tissues

  • Author(s): Da-Ping Yang 1 ; Hui-Ping Lu 2 ; Gang Chen 2 ; Jie Yang 3 ; Li Gao 2 ; Jian-Hua Song 1 ; Shang-Wei Chen 4 ; Jun-Xian Mo 5 ; Jin-Liang Kong 6 ; Zhong-Qing Tang 7 ; Chang-Bo Li 5 ; Hua-Fu Zhou 4 ; Lin-Jie Yang 2
    • View affiliations
  • Source: Volume 14, Issue 5, October 2020, p. 252 – 260
    DOI:  10.1049/iet-syb.2020.0063 , Print ISSN 1751-8849, Online ISSN 1751-8857
© The Institution of Engineering and Technology
Received 09/06/2020, Accepted 10/08/2020, Revised 01/08/2020, Published 17/08/2020

This study aimed to investigate the clinicopathological significance and prospective molecular mechanism of RUNX family transcription factor 2 (RUNX2) in lung squamous cell carcinoma (LUSC). The authors used immunohistochemistry (IHC), RNA-seq, and microarray data from multi-platforms to conduct a comprehensive analysis of the clinicopathological significance and molecular mechanism of RUNX2 in the occurrence and development of LUSC. RUNX2 expression was significantly higher in 16 LUSC tissues than in paired non-cancerous tissues detected by IHC (P < 0.05). RNA-seq data from the combination of TCGA and genotype-tissue expression (GTEx) revealed significantly higher expression of RUNX2 in 502 LUSC samples than in 476 non-cancer samples. The expression of RUNX2 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples (P = 0.031). The pooled standardised mean difference (SMD) for RUNX2 was 0.87 (95% CI, 0.58–1.16), including 29 microarrays from GEO and one from ArrayExpress. The co-expression network of RUNX2 revealed complicated connections between RUNX2 and 45 co-expressed genes, which were significantly clustered in pathways including ECM-receptor interaction, focal adhesion, protein digestion and absorption, human papillomavirus infection and PI3K-Akt signalling pathway. Overexpression of RUNX2 plays an essential role in the clinical progression of LUSC.

Inspec keywords: cancer; biological tissues; RNA; cellular biophysics; bioinformatics; adhesion; gynaecology; genetics; molecular biophysics; tumours; lung; biochemistry; proteins; bone; biological organs

Other keywords: lung squamous cell carcinoma tissues; RUNX family transcription factor 2; RUNX2 expression; RUNX2 upregulation; RUNX2 protein

Subjects: Cellular biophysics; Biomolecular structure, configuration, conformation, and active sites; Biomolecular interactions, charge transfer complexes; Physical chemistry of biomolecular solutions and condensed states; Biology and medical computing; Patient diagnostic methods and instrumentation; Physics of subcellular structures; Probability theory, stochastic processes, and statistics

References

    1. 1)
      • 32. Ji, M., Li, W., He, G., et al: ‘Zinc-α2-glycoprotein 1 promotes EMT in colorectal cancer by filamin A mediated focal adhesion pathway’, J. Cancer, 2019, 10, (22), pp. 5557–5566.
    2. 2)
      • 34. Bai, X., Meng, L., Sun, H., et al: ‘MicroRNA-196b inhibits cell growth and metastasis of lung cancer cells by targeting Runx2’, Cell. Physiol. Biochem., 2017, 43, (2), pp. 757–767.
    3. 3)
      • 2. Li, W., Li, X., Gao, L.N., et al: ‘Integrated analysis of the functions and prognostic values of RNA binding proteins in lung squamous cell carcinoma’, Front. Genet., 2020, 11, p. 185.
    4. 4)
      • 15. Nagy, Á., Lánczky, A., Menyhárt, O., et al: ‘Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets’, Sci. Rep., 2018, 8, (1), p. 9227.
    5. 5)
      • 33. Hsu, Y.L., Huang, M.S., Yang, C.J., et al: ‘Lung tumor-associated osteoblast-derived bone morphogenetic protein-2 increased epithelial-to-mesenchymal transition of cancer by Runx2/snail signaling pathway’, J. Biol. Chem., 2011, 286, (43), pp. 37335–37346.
    6. 6)
      • 1. Siegel, R.L., Miller, K.D., Jemal, A.: ‘Cancer statistics, 2020’, CA Cancer J. Clin., 2020, 70, (1), pp. 7–30.
    7. 7)
      • 20. Yue, Z., Chu, X., Xia, J.: ‘PredCID: prediction of driver frameshift indels in human cancer’, Brief. Bioinform., 2020, 26, p. bbaa119.
    8. 8)
      • 17. Jiao, X.D., He, X., Qin, B.D., et al: ‘The prognostic value of tumor mutation burden in EGFR-mutant advanced lung adenocarcinoma, an analysis based on cBioPortal data base’, J. Thorac. Dis., 2019, 11, (11), pp. 4507–4515.
    9. 9)
      • 29. Zhang, H.J., Tao, J., Sheng, L., et al: ‘Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway’, Onco. Targets Ther., 2016, 9, pp. 1801–1812.
    10. 10)
      • 27. Cheng, H., Jiang, X., Zhang, Q., et al: ‘Naringin inhibits colorectal cancer cell growth by repressing the PI3 K/AKT/mTOR signaling pathway’, Exp. Ther. Med., 2020, 19, (6), pp. 3798–3804.
    11. 11)
      • 31. Brandão-Costa, R.M., Helal-Neto, E., Vieira, A.M., et al: ‘Extracellular matrix derived from high metastatic human breast cancer triggers epithelial-mesenchymal transition in epithelial breast cancer cells through αvβ3 integrin’, Int. J. Mol. Sci., 2020, 21, (8), p. 2995.
    12. 12)
      • 24. Jiang, L., Yu, X., Ma, X., et al: ‘Identification of transcription factor-miRNA-lncRNA feed-forward loops in breast cancer subtypes’, Comput. Biol. Chem., 2019, 78, pp. 1–7.
    13. 13)
      • 22. Jiang, C., Cao, S., Li, N., et al: ‘PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer’, Cancer Cell Int., 2019, 19, p. 233.
    14. 14)
      • 11. Liang, L., Zhao, K., Zhu, J.H., et al: ‘Comprehensive evaluation of FKBP10 expression and its prognostic potential in gastric cancer’, Oncol. Rep., 2019, 42, (2), pp. 615–628.
    15. 15)
      • 6. Huang, J., Chang, S., Lu, Y., et al: ‘Enhanced osteopontin splicing regulated by RUNX2 is HDAC-dependent and induces invasive phenotypes in NSCLC cells’, Cancer Cell Int., 2019, 19, p. 306.
    16. 16)
      • 26. Xie, J., Yu, F., Li, D., et al: ‘MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2’, Tumour Biol., 2016, 37, (1), pp. 1197–1204.
    17. 17)
      • 28. Zhang, K., Wang, J., Wang, J., et al: ‘LKB1 deficiency promotes proliferation and invasion of glioblastoma through activation of mTOR and focal adhesion kinase signaling pathways’, Am. J. Cancer Res., 2019, 9, (8), pp. 1650–1663.
    18. 18)
      • 5. Zuo, Z., Ye, F., Liu, Z., et al: ‘MicroRNA-153 inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition in breast cancer via direct targeting of RUNX2’, Exp. Ther. Med., 2019, 17, (6), pp. 4693–4702.
    19. 19)
      • 23. Li, R., Liu, J., Qi, J.: ‘Knockdown of long non-coding RNA CCAT1 suppresses proliferation and EMT of human cervical cancer cell lines by down-regulating Runx2’, Exp. Mol. Pathol., 2020, 113, p. 104380.
    20. 20)
      • 18. Folkman, L., Yang, Y., Li, Z., et al: ‘DDIG-in: detecting disease-causing genetic variations due to frameshifting indels and nonsense mutations employing sequence and structural properties at nucleotide and protein levels’, Bioinformatics, 2015, 31, (10), pp. 1599–1606.
    21. 21)
      • 16. Buechner, P., Hinderer, M., Unberath, P., et al: ‘Requirements analysis and specification for a molecular tumor board platform based on cBioPortal’, Diagnostics (Basel), 2020, 10, (2), p. 93.
    22. 22)
      • 30. Herreño, A.M., Ramírez, A.C., Chaparro, V.P., et al: ‘Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer: epigenetic control of the RUNX2 P1 promoter’, Tumour Biol., 2019, 41, (5), p. 1010428319851014.
    23. 23)
      • 4. Zhang, N., Wang, H., Xie, Q., et al: ‘Identification of potential diagnostic and therapeutic target genes for lung squamous cell carcinoma’, Oncol. Lett., 2019, 18, (1), pp. 169–180.
    24. 24)
      • 13. Li, C., Qin, F., Hong, H., et al: ‘Identification of flap endonuclease 1 as a potential core gene in hepatocellular carcinoma by integrated bioinformatics analysis’, PeerJ, 2019, 7, p. e7619.
    25. 25)
      • 14. Győrffy, B., Surowiak, P., Budczies, J., et al: ‘Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer’, PLoS One, 2013, 8, (12), p. e82241.
    26. 26)
      • 21. Langfelder, P., Horvath, S.: ‘WGCNA: an R package for weighted correlation network analysis’, BMC Bioinformatics, 2008, 9, p. 559.
    27. 27)
      • 19. Cheng, N., Li, M., Zhao, L., et al: ‘Comparison and integration of computational methods for deleterious synonymous mutation prediction’, Brief. Bioinform., 2020, 21, (3), pp. 970–981.
    28. 28)
      • 7. Li, H., Zhou, R.J., Zhang, G.Q., et al: ‘Clinical significance of RUNX2 expression in patients with non-small cell lung cancer: a 5-year follow-up study’, Tumour Biol., 2013, 34, (3), pp. 1807–1812.
    29. 29)
      • 25. Si, W., Zhou, J., Zhao, Y., et al: ‘SET7/9 promotes multiple malignant processes in breast cancer development via RUNX2 activation and is negatively regulated by TRIM21’, Cell Death Dis., 2020, 11, (2), p. 151.
    30. 30)
      • 10. Zheng, Q.W., Zhou, Y.L., You, Q.J., et al: ‘WWOX inhibits the invasion of lung cancer cells by downregulating RUNX2’, Cancer Gene Ther., 2016, 23, (12), pp. 433–438.
    31. 31)
      • 8. Herreño, A.M., Ramírez, A.C., Chaparro, V.P., et al: ‘Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer: epigenetic control of the RUNX2 P1 promoter’, Tumour Biol., 2019, 41, (5), p. 1010428319851014.
    32. 32)
      • 9. Tandon, M., Gokul, K., Ali, S.A., et al: ‘Runx2 mediates epigenetic silencing of the bone morphogenetic protein-3B (BMP-3B/GDF10) in lung cancer cells’, Mol. Cancer, 2012, 11, p. 27.
    33. 33)
      • 3. Wang, X., Liao, X., Huang, K., et al: ‘Clustered microRNAs hsa-miR-221–3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma’, J. Cancer, 2019, 10, (11), pp. 2520–2533.
    34. 34)
      • 12. Gao, L., Xiong, D.D., He, R.Q., et al: ‘MIR22HG as a tumor suppressive lncRNA In HCC: a comprehensive analysis integrating RT-qPCR, mRNA-seq, and microarrays’, Onco. Targets Ther., 2019, 12, pp. 9827–9848.
http://iet.metastore.ingenta.com/content/journals/10.1049/iet-syb.2020.0063
Loading

Related content

content/journals/10.1049/iet-syb.2020.0063
pub_keyword,iet_inspecKeyword,pub_concept
6
6
Loading
Print this page
This is a required field
Please enter a valid email address