FOXM1 and UBE2C Are Distinct Biomarkers for Non-Small Cell Lung Cancer Survival Prediction: Data-Mining Based on ONCOMINE

Authors

  • Ya Wang West China School of Medicine Sichuan University
  • Jiang Zhu Sichuan University

DOI:

https://doi.org/10.30564/jams.v2i2.611

Abstract

Non-small cell lung cancer (NSCLC) remains to be primary reason of tumor deaths in the past few decades. The mortality of this malignancy could be reduced by developing new prognostic biomarkers and discovering novel therapeutic biological target. Here, we studied the mRNA expression of FOX gene family and UBE2C in different types of cancer compared with normal tissue through ONCOMINE differential analysis. CCLE analysis was mined to explore the expression profiles of target genes in different tumor cells. GEPIA was used to discover the expression of target genes in different subtypes and the correlation with lung cancer stage. The prognostic values of FOXM1 and UBE2C were further investigated through Kaplan-Meier plotter analysis. It showed that FOXA1, FOXD1 and FOXM1 were dramatically high expressed in NSCLC comparing with normal lung tissues. Besides, the expression of FOXM1 was significantly associated with UBE2C. Furthermore, the overexpression of FOXM1 and UBE2C were correlated to shorter survival in lung adenocarcinoma (LAC) instead of lung squamous cell carcinoma(LSCC).

Hence, we could draw a conclusion that FOXM1 and UBE2C are distinguished biomarkers and crucial prognostic indicators for lung adenocarcinoma patients.

Keywords:

FOXM1, FOX gene family, UBE2C, Biomarkers, Non-small cell lung cancer, Lung cancer, Prognosis

References

[1] Yokota J, Kohno T. Molecular footprints of human lung cancer progression. Cancer Sci 2004, 95:197-204.

[2] DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin 2014, 64:252-271.

[3] Wei S, Tian J, Song X, et al. Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database. J Cancer Res Clin Oncol 2018, 144:145-155.

[4] Jackson BC, Carpenter C, Nebert DW, et al. Update of human and mouse forkhead box (FOX) gene families. Hum Genomics 2010, 4:345-352.

[5] Hannenhalli S, Kaestner KH. The evolution of Fox genes and their role in development and disease. Nat Rev Genet 2009, 10:233-240.

[6] Miao L, Xiong X, Lin Y, et al. Down-regulation of FoxM1 leads to the inhibition of the epithelial-mesenchymal transition in gastric cancer cells. Cancer Genet 2014, 207:75-82.

[7] Wang M, Gartel AL. The suppression of FOXM1 and its targets in breast cancer xenograft tumors by siRNA. Oncotarget 2011, 2:1218-1226.

[8] Koo CY, Muir KW, Lam EW: FOXM1.From cancer initiation to progression and treatment. Biochim Biophys Acta 2012, 1819:28-37.

[9] Maachani UB, Shankavaram U, Kramp T, et al. FOXM1 and STAT3 interaction confers radioresistance in glioblastoma cells. Oncotarget 2016, 7:77365-77377.

[10] Nicolau-Neto P, Palumbo A, De Martino M, et al. UBE2C Is a Transcriptional Target of the Cell Cycle Regulator FOXM1. Genes (Basel) 2018,9.

[11] Townsley FM, Aristarkhov A, Beck S, et al. Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase. Proc Natl Acad Sci USA 1997, 94:2362-2367.

[12] Hao Z, Zhang H, Cowell J. Ubiquitin-conjugating enzyme UBE2C: molecular biology, role in tumorigenesis, and potential as a biomarker. Tumour Biol 2012, 33:723-730.

[13] Bavi P, Uddin S, Ahmed M, et al. Bortezomib stabilizes mitotic cyclins and prevents cell cycle progression via inhibition of UBE2C in colorectal carcinoma. Am J Pathol 2011, 178:2109-2120.

[14] Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 2017, 45:W98-W102.

[15] Gyorffy 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:e82241.

[16] Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017, 67:7-30.

[17] Sun C, Liu Z, Li S, et al. Down-regulation of c-Met and Bcl2 by microRNA-206, activates apoptosis, and inhibits tumor cell proliferation, migration and colony formation. Oncotarget 2015, 6:25533-25574.

[18] Sun C, Sang M, Li S, et al. Hsa-miR-139-5p inhibits proliferation and causes apoptosis associated with down-regulation of c-Met. Oncotarget 2015, 6:39756-39792.

[19] Gan HY, Li N, Zhang Q, et al. Silencing FOXA1 gene regulates liver cancer cell apoptosis and cell proliferation. Eur Rev Med Pharmacol Sci 2018, 22:397-404.

[20] Bernardo GM, Keri RA: FOXA1: a transcription factor with parallel functions in development and cancer. Biosci Rep 2012, 32:113-130.

[21] Zhao YF, Zhao JY, Yue H, et al. FOXD1 promotes breast cancer proliferation and chemotherapeutic drug resistance by targeting p27. Biochem Biophys Res Commun 2015;456:232-237.

[22] van der Heul-Nieuwenhuijsen L, Dits NF, Jenster G. Gene expression of forkhead transcription factors in the normal and diseased human prostate. BJU Int 2009, 103:1574-1580.

[23] Ju W, Yoo BC, Kim IJ, et al. Identification of genes with differential expression in chemoresistant epithelial ovarian cancer using high-density oligonucleotide microarrays. Oncol Res 2009, 18:47-56.

[24] Nakayama S, Soejima K, Yasuda H, et al. FOXD1 Expression Is Associated with Poor Prognosis in Non-small Cell Lung Cancer. Anticancer Research 2015, 35:261-268.

[25] Ahmed M, Uddin S, Hussain AR, et al. FoxM1 and its association with matrix metalloproteinases (MMP) signaling pathway in papillary thyroid carcinoma. J Clin Endocrinol Metab 2012, 97:E1-E13.

[26] Milewski D, Balli D, Ustiyan V, et al. FOXM1 activates AGR2 and causes progression of lung adenomas into invasive mucinous adenocarcinomas. PLoS Genet 2017, 13:e1007097.

[27] Guo L, Ding Z, Huang N, et al. Forkhead Box M1 positively regulates UBE2C and protects glioma cells from autophagic death. Cell Cycle 2017, 16:1705-1718.

[28] Zhang Y, Tian S, Li X, et al. UBE2C promotes rectal carcinoma via miR-381. Cancer Biol Ther 2018, 19:230-238.

[29] Zhang HQ, Zhao G, Ke B, et al. Overexpression of UBE2C correlates with poor prognosis in gastric cancer patients. Eur Rev Med Pharmacol Sci 2018, 22:1665-1671.

[30] Li L, Li X, Wang W, et al. UBE2C is involved in the functions of ECRG4 on esophageal squamous cell carcinoma. Biomed Pharmacother 2018, 98:201-206.

[31] Zhang Z, Liu P, Wang J, et al. Ubiquitin-conjugating enzyme E2C regulates apoptosis-dependent tumor progression of non-small cell lung cancer via ERK pathway. Med Oncol 2015, 32:149.

Downloads

Issue

Article Type

Research Article