Research article Special Issues

KLHL14, an ovarian and endometrial-specific gene, is over-expressed in ovarian and endometrial cancer

  • Received: 25 May 2019 Accepted: 12 November 2019 Published: 11 December 2019
  • Ovarian cancer (OC) and endometrial cancer (EC) are two types of the most frequent gynecological malignancies worldwide. However, the prognosis of OC and EC patients remained gloomy. Therefore, there was still an urgent need to identify new biomarkers for early diagnosis and treatment of OC and EC. TCGA datasets were used to screen the KLHL14 expression levels in 18 different types of human cancers. TCGA datasets were also used to analyze the association between KLHL14 expression levels and OS/PFS in OC and EC. Human Protein Atlas was used to detected the KLHL14 protein levels in OC and EC. Kaplan-Meier plotter was used to evaluate the prognostic values of KLHL14 in Ovarian cancer. MAS 3.0 was used to perform GO and KEGG pathway analysis. STRING was used to perform PPI network. KLHL14 was specially expressed in OC and EC samples. Moreover, KLHL14 was found to be up-regulated in all stage of OC and EC samples. By analyzing Kaplan-Meier plotter and TCGA datasets, we found higher KLHL14 expression level was associated with shorter overall and progression-free survival in both OC and EC patients. Furthermore, GO and KEGG analysis of KLHL14 co-expressing genes indicated it played important roles in OC and EC progression. We for the first time reported KLHL14 was specially over-expressed in ovarian and endometrial cancer, up-regulation of KLHL14 was positively associated with worse outcome. Finally, we found knockdown of KLHL14 suppressed OC cell proliferation. KLHL14 could be a potential biomarker and therapy target for OC and EC.

    Citation: Mi Han, Huajing Yang, Qin Lin. KLHL14, an ovarian and endometrial-specific gene, is over-expressed in ovarian and endometrial cancer[J]. Mathematical Biosciences and Engineering, 2020, 17(2): 1702-1717. doi: 10.3934/mbe.2020089

    Related Papers:

  • Ovarian cancer (OC) and endometrial cancer (EC) are two types of the most frequent gynecological malignancies worldwide. However, the prognosis of OC and EC patients remained gloomy. Therefore, there was still an urgent need to identify new biomarkers for early diagnosis and treatment of OC and EC. TCGA datasets were used to screen the KLHL14 expression levels in 18 different types of human cancers. TCGA datasets were also used to analyze the association between KLHL14 expression levels and OS/PFS in OC and EC. Human Protein Atlas was used to detected the KLHL14 protein levels in OC and EC. Kaplan-Meier plotter was used to evaluate the prognostic values of KLHL14 in Ovarian cancer. MAS 3.0 was used to perform GO and KEGG pathway analysis. STRING was used to perform PPI network. KLHL14 was specially expressed in OC and EC samples. Moreover, KLHL14 was found to be up-regulated in all stage of OC and EC samples. By analyzing Kaplan-Meier plotter and TCGA datasets, we found higher KLHL14 expression level was associated with shorter overall and progression-free survival in both OC and EC patients. Furthermore, GO and KEGG analysis of KLHL14 co-expressing genes indicated it played important roles in OC and EC progression. We for the first time reported KLHL14 was specially over-expressed in ovarian and endometrial cancer, up-regulation of KLHL14 was positively associated with worse outcome. Finally, we found knockdown of KLHL14 suppressed OC cell proliferation. KLHL14 could be a potential biomarker and therapy target for OC and EC.


    加载中


    [1] R. L. Siegel, K. D. Miller, A. Jemal, Colorectal cancer Statistics 2017, CA Cancer J. Clin., 67 (2017), 177-193.
    [2] J. Hunn, G. C. Rodriguez, Ovarian cancer: Etiology, risk factors, and epidemiology, Clin. Obstet. Gynecol., 55 (2012), 3-23.
    [3] X. L. Yu, Z. X. L, R. H, Y. J. Nie, R. S. Chen, Nerve growth factor and its receptors on onset and diagnosis of ovarian cancer, Oncol. Lett., 14 (2017), 2864-2868.
    [4] E. Gov, M. Kori, K. Y. Arga, Multiomics analysis of tumor microenvironment reveals gata2 and miRNA-124-3p as potential novel biomarkers in ovarian cancer, OMICS J. Integr. Biol., 21 (2017), 603-615.
    [5] M. K. Tang, A. S. Wong, Exosomes: Emerging biomarkers and targets for ovarian cancer, Cancer Lett., 367 (2015), 26-33.
    [6] W. Wei, S. C. Mok, E. Oliva, S. H. Kim, G. Mohapatra, M. J. Birrer, FGF18 as a prognostic and therapeutic biomarker in ovarian cancer, J. Clin. Invest., 123 (2013), 4435-4448.
    [7] Cancer Genome Atlas Research Network, Integrated genomic analyses of ovarian carcinoma, Nature, 474 (2011), 609-615.
    [8] Y. Liu, W. Li, X. Li, Y. Tai, Q. Lu, N. Yang, et al., Expression and significance of biglycan in endometrial cancer, Arch. Gynecol. Obstet., 289 (2014), 649-655.
    [9] W. Tian, Y. Zhu, Y. Wang, F. Teng, H. Zhang, G. Liu, et al., Visfatin, a potential biomarker and prognostic factor for endometrial cancer, Gynecol. Oncol., 129 (2013), 505-512.
    [10] B. S. Dhanoa, T. Cogliati, A. G. Satish, E. A. Bruford, J. S. Friedman, Update on the Kelch-like (KLHL) gene family, Hum. Genomics, 7 (2013), 13.
    [11] E. V. Koonin, T. G. Senkevich, V. I. Chernos, A family of DNA virus genes that consists of fused portions of unrelated cellular genes, Trends. Biochem. Sci., 17 (1992), 213-214.
    [12] W. C. Yuan, Y. R. Lee, S. F. Huang, Y. M. Lin, T. Y. Chen, H. C. Chung, et al., A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression, Cancer Cell, 20 (2011), 214-228.
    [13] P. H. Chen, T. J. Smith, J. Wu, P. F. Siesser, B. J. Bisnett, F. Khan, et al., Glycosylation of KEAP1 links nutrient sensing to redox stress signaling, EMBO J., 36 (2017), 2233-2250.
    [14] X. Wu, J. Miao, J. Jiang, F. Liu, Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers, Eur. J. Obstet. Gynecol. Reprod. Biol., 217 (2017), 161-166.
    [15] M. Uhlen, L. Fagerberg, B. M. Hallstrom, C. Lindskog, P. Oksvold, A. Mardinoglu, et al., Tissue-based map of the human proteome, Science, 347 (2015), 1260419-1260419. doi: 10.1126/science.1260419
    [16] A. Lanczky, A. Nagy, G. Bottai, G. Munkacsy, A. Szabo, L. Santarpia, et al., MiRpower: A web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients, Breast Cancer Res. Treat, 160 (2016), 439-446.
    [17] D. W. Huang, B. T. Sherman, R. A. Lempicki, Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources, Nat. Protoc., 4 (2009), 44-57.
    [18] D. W. Huang, B. T. Sherman, R. A. Lempicki, Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists, Nucleic Acids Res., 37 (2009), 1-13.
    [19] J. Gao, B. A. Aksoy, U. Dogrusoz, G. Dresdner, B. Gross, S. O. Sumer, et al., Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal, Sci. Signal, 6 (2013), l1.
    [20] E. Cerami, J. Gao, U. Dogrusoz, B. E. Gross, S. O. Sumer, B. A. Aksoy, et al., The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data, Cancer Discov., 2 (2012), 401-404.
    [21] H. G. Xiong, H. Li, Y. Xiao, Q. C. Yang, L. L. Yang, L. Chen, et al., Long noncoding RNA MYOSLID promotes invasion and metastasis by modulating the partial epithelial-mesenchymal transition program in head and neck squamous cell carcinoma, J. Exp. Clin. Cancer Res., 38 (2019), 278.
    [22] D. Szklarczyk, J. H. Morris, H. Cook, M. Kuhn, S. Wyder, M. Simonovic, et al., The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible, Nucleic Acids Res., 45 (2017), 362-368. doi: 10.1093/nar/gkw937
    [23] Y. Miao, M. Lu, Q. Yan, S. Li, Y. Feng, Inhibition of proliferation, migration, and invasion by knockdown of pyruvate Kinase-M2 (PKM2) in ovarian cancer SKOV3 and OVCAR3 cells, Oncol. Res., 24 (2016), 463-475.
    [24] M. Ma, N. Yu, Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer, Tohoku. J. Exp. Med., 241 (2017), 239-247.
    [25] D. Wang, X. Cao, Y. Zhang, Y. Liu, C. Yao, W. Ge, et al., LAMP3 expression correlated with poor clinical outcome in human ovarian cancer, Tumour Biol., 39 (2017).
    [26] L. Huang, Y. Zhou, X. P. Cao, J. X. Lin, L. Zhang, S. T. Huang, et al., KPNA2 is a potential diagnostic serum biomarker for epithelial ovarian cancer and correlates with poor prognosis, Tumour Biol., 39 (2017).
    [27] J. Lin, L. Zhang, H. Huang, Y. Huang, L. Huang, J. Wang, et al., MiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4, Oncotarget, 6 (2015), 23793-23806.
    [28] F. F. Zhu, F. Y. Zheng, H. O. Wang, J. J. Zheng, Q. Zhang, Downregulation of lncRNA TUBA4B is Associated with Poor Prognosis for Epithelial Ovarian Cancer, Pathol. Oncol. Res., 24 (2018), 419-425.
    [29] M. Fu, R. Rao, D. Sudhakar, C. P. Hogue, Z. Rutta, S. Morales, et al., Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src, PLoS One, 6 (2011), e19945.
    [30] M. Wadehra, S. Natarajan, D. B. Seligson, C. J. Williams, A. J. Hummer, C. Hedvat, et al., Expression of epithelial membrane protein-2 is associated with endometrial adenocarcinoma of unfavorable outcome, Cancer, 107 (2006), 90-98. doi: 10.1002/cncr.21957
    [31] O. Habeeb, L. Goodglick, R. A. Soslow, R. G. Rao, L. K. Gordon, O. Schirripa, et al., Epithelial membrane protein-2 expression is an early predictor of endometrial cancer development, Cancer, 116 (2010), 4718-4726.
    [32] K. Yamawaki, T. Ishiguro, Y. Mori, K. Yoshihara, K. Suda, R. Tamura, et al., Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer, Cancer Sci., 108 (2017), 632-640.
  • Reader Comments
  • © 2020 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(5073) PDF downloads(574) Cited by(3)

Article outline

Figures and Tables

Figures(7)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog