Open Access

CFHR1 is a potentially downregulated gene in lung adenocarcinoma

  • Authors:
    • Geting Wu
    • Yuanliang Yan
    • Xiang Wang
    • Xinxin Ren
    • Xi Chen
    • Shuangshuang Zeng
    • Jie Wei
    • Long Qian
    • Xue Yang
    • Chunlin Ou
    • Wei Lin
    • Zhicheng Gong
    • Jianhua Zhou
    • Zhijie Xu
  • View Affiliations

  • Published online on: September 3, 2019     https://doi.org/10.3892/mmr.2019.10644
  • Pages: 3642-3648
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

There is increasing evidence that human complement factor H‑related protein 1 (CFHR1) plays a crucial role in the development of malignant diseases. However, few studies have identified the roles of CFHR1 in the occurrence and prognosis of lung adenocarcinoma (LADC). In the present study, comprehensive bioinformatic analyses of data obtained from the Oncomine platform, UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that CFHR1 expression is significantly reduced in both LADC tissues and cancer cells. The patients presenting with downregulation of CFHR1 had significantly lower overall survival (OS) and post progression survival (PPS) times. Through analysis of the datasets from Gene Expression Omnibus database, we found that the compound actinomycin D promoted CFHR1 expression, further displaying the cytotoxic effect in the LADC cell line A549. In addition, the expression level of CFHR1 in the cisplatin‑resistant LADC cell line CDDP‑R (derived from H460) was also significantly reduced. Our research demonstrated that low levels of CFHR1 are specifically found in LADC samples, and CFHR1 could serve as a potential therapeutic target for this subset of lung cancers. Determination of the detailed roles of CFHR1 in LADC biology could provide insightful information for further investigations.

References

1 

Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL and Paz-Ares L: Lung cancer: Current therapies and new targeted treatments. Lancet. 389:299–311. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Wei J, Yan Y, Chen X, Qian L, Zeng S, Li Z, Dai S, Gong Z and Xu Z: The roles of plant-derived Triptolide on non-small cell lung cancer. Oncol Res. 27:849–858. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Ulahannan D, Khalifa J, Faivre-Finn C and Lee SM: Emerging treatment paradigms for brain metastasis in non-small-cell lung cancer: An overview of the current landscape and challenges ahead. Ann Oncol. 28:2923–2931. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Zhou S, Yan Y, Chen X, Wang X, Zeng S, Qian L, Wei J, Yang X, Zhou Y, Gong Z and Xu Z: Roles of highly expressed PAICS in lung adenocarcinoma. Gene. 692:1–8. 2019. View Article : Google Scholar : PubMed/NCBI

5 

Zhang R, Sun S, Ji F, Liu C, Lin H, Xie L, Yang H, Tang W, Zhou Y, Xu J and Li P: CNTN-1 enhances chemoresistance in human lung adenocarcinoma through induction of epithelial-mesenchymal transition by targeting the PI3K/Akt pathway. Cell Physiol Biochem. 43:465–480. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Yan Y, Su W, Zeng S, Qian L, Chen X, Wei J, Chen N, Gong Z and Xu Z: Effect and mechanism of tanshinone i on the radiosensitivity of lung cancer cells. Mol Pharm. 15:4843–4853. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Skerka C, Chen Q, Fremeaux-Bacchi V and Roumenina LT: Complement factor H related proteins (CFHRs). Mol Immunol. 56:170–180. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Rogers LM, Mott SL, Smith BJ, Link BK, Sahin D and Weiner GJ: Complement-regulatory proteins CFHR1 and CFHR3 and patient response to anti-CD20 monoclonal antibody therapy. Clin Cancer Res. 23:954–961. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Hageman GS, Hancox LS, Taiber AJ, Gehrs KM, Anderson DH, Johnson LV, Radeke MJ, Kavanagh D, Richards A, Atkinson J, et al: Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: Characterization, ethnic distribution and evolutionary implications. Ann Med. 38:592–604. 2006. View Article : Google Scholar :

10 

Jullien P, Laurent B, Claisse G, Masson I, Dinic M, Thibaudin D, Berthoux F, Alamartine E, Mariat C and Maillard N: Deletion Variants of CFHR1 and CFHR3 associate with mesangial immune deposits but not with progression of IgA nephropathy. J Am Soc Nephrol. 29:661–669. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Fratelli M, Bolis M, Kurosaki M, Dori M, Guarnaccia V, Spinelli O, Alberti M, Valoti E, Pileggi S, Noris M, et al: Association of CFHR1 homozygous deletion with acute myelogenous leukemia in the European population. Leuk Lymphoma. 57:1234–1237. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Cui L, Fu J, Pang JC, Qiu ZK, Liu XM, Chen FR, Shi HL, Ng HK and Chen ZP: Overexpression of IL-7 enhances cisplatin resistance in glioma. Cancer Biol Ther. 13:496–503. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, Barrette TR, Anstet MJ, Kincead-Beal C, Kulkarni P, et al: Oncomine 3.0: Genes, pathways and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 9:166–180. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK and Varambally S: UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 19:649–658. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Tang Z, Li C, Kang B, Gao G, Li C and Zhang Z: GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45:W98–W102. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L and Győrffy B: miRpower: A web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 160:439–446. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Yan Y, Xu Z, Hu X, Qian L, Li Z, Zhou Y, Dai S, Zeng S and Gong Z: SNCA is a functionally low-expressed gene in lung adenocarcinoma. Genes (Basel). 9:E162018. View Article : Google Scholar : PubMed/NCBI

18 

Wang Z, Lecane PS, Thiemann P, Fan Q, Cortez C, Ma X, Tonev D, Miles D, Naumovski L, Miller RA, et al: Synthesis and biologic properties of hydrophilic sapphyrins, a new class of tumor-selective inhibitors of gene expression. Mol Cancer. 6:92007. View Article : Google Scholar : PubMed/NCBI

19 

Sun Y, Zheng S, Torossian A, Speirs CK, Schleicher S, Giacalone NJ, Carbone DP, Zhao Z and Lu B: Role of insulin-like growth factor-1 signaling pathway in cisplatin-resistant lung cancer cells. Int J Radiat Oncol Biol Phys. 82:e563–e572. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, et al: Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 6:pl12013. View Article : Google Scholar : PubMed/NCBI

21 

Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, et al: The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45:D362–D368. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Su G, Morris JH, Demchak B and Bader GD: Biological network exploration with Cytoscape 3. Curr Protoc Bioinformatics. 47:8.13.1–24. 2014. View Article : Google Scholar

23 

Wang J, Vasaikar S, Shi Z, Greer M and Zhang B: WebGestalt 2017: A more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit. Nucleic Acids Res. 45:W130–W137. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Luo W, Pant G, Bhavnasi YK, Blanchard SG Jr and Brouwer C: Pathview Web: User friendly pathway visualization and data integration. Nucleic Acids Res. 45:W501–W508. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, et al: Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA. 98:13790–13795. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, Lin L, Chen G, Gharib TG, Thomas DG, et al: Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med. 8:816–824. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Zhou H, Vallieres M, Bai HX, Su C, Tang H, Oldridge D, Zhang Z, Xiao B, Liao W, Tao Y, et al: MRI features predict survival and molecular markers in diffuse lower-grade gliomas. Neuro Oncol. 19:862–870. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Hannan JP, Laskowski J, Thurman JM, Hageman GS and Holers VM: Mapping the complement factor H-related protein 1 (CFHR1):C3b/C3d interactions. PLoS One. 11:e01662002016. View Article : Google Scholar : PubMed/NCBI

29 

Trojnar E, Józsi M, Uray K, Csuka D, Szilágyi Á, Milosevic D, Stojanović VD, Spasojević B, Rusai K, Müller T, et al: Analysis of linear antibody epitopes on factor H and CFHR1 using sera of patients with autoimmune atypical hemolytic uremic syndrome. Front Immunol. 8:3022017. View Article : Google Scholar : PubMed/NCBI

30 

Valoti E, Alberti M, Tortajada A, Garcia-Fernandez J, Gastoldi S, Besso L, Bresin E, Remuzzi G, Rodriguez de Cordoba S and Noris M: A novel atypical hemolytic uremic syndrome-associated hybrid CFHR1/CFH gene encoding a fusion protein that antagonizes factor H-dependent complement regulation. J Am Soc Nephrol. 26:209–219. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Guo X, Hao Y, Kamilijiang M, Hasimu A, Yuan J, Wu G, Reyimu H, Kadeer N and Abudula A: Potential predictive plasma biomarkers for cervical cancer by 2D-DIGE proteomics and ingenuity pathway analysis. Tumour Biol. 36:1711–1720. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Arya SK and Estrela P: Electrochemical ELISA-based platform for bladder cancer protein biomarker detection in urine. Biosens Bioelectron. 117:620–627. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Charbonneau B, Maurer MJ, Fredericksen ZS, Zent CS, Link BK, Novak AJ, Ansell SM, Weiner GJ, Wang AH, Witzig TE, et al: Germline variation in complement genes and event-free survival in follicular and diffuse large B-cell lymphoma. Am J Hematol. 87:880–885. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Jullien P, Laurent B, Claisse G, Masson I, Dinic M, Thibaudin D, Berthoux F, Alamartine E, Mariat C and Maillard N: Deletion variants of CFHR1 and CFHR3 associate with mesangial immune deposits but not with progression of IgA nephropathy. J Am Soc Nephrol. 29:661–669. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Lamano JB, Lamano JB, Li YD, DiDomenico JD, Choy W, Veliceasa D, Oyon DE, Fakurnejad S, Ampie L, Kesavabhotla K, et al: Glioblastoma-derived IL6 induces immunosuppressive peripheral myeloid cell PD-L1 and promotes tumor growth. Clin Cancer Res. 25:3643–3657. 2019. View Article : Google Scholar : PubMed/NCBI

36 

Bustelo XR and Dosil M: Ribosome biogenesis and cancer: basic and translational challenges. Curr Opin Genet Dev. 48:22–29. 2018. View Article : Google Scholar : PubMed/NCBI

37 

de la Cruz J, Gómez-Herreros F, Rodríguez-Galán O, Begley V, de la Cruz Muñoz-Centeno M and Chávez S: Feedback regulation of ribosome assembly. Curr Genet. 64:393–404. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2019
Volume 20 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wu, G., Yan, Y., Wang, X., Ren, X., Chen, X., Zeng, S. ... Xu, Z. (2019). CFHR1 is a potentially downregulated gene in lung adenocarcinoma. Molecular Medicine Reports, 20, 3642-3648. https://doi.org/10.3892/mmr.2019.10644
MLA
Wu, G., Yan, Y., Wang, X., Ren, X., Chen, X., Zeng, S., Wei, J., Qian, L., Yang, X., Ou, C., Lin, W., Gong, Z., Zhou, J., Xu, Z."CFHR1 is a potentially downregulated gene in lung adenocarcinoma". Molecular Medicine Reports 20.4 (2019): 3642-3648.
Chicago
Wu, G., Yan, Y., Wang, X., Ren, X., Chen, X., Zeng, S., Wei, J., Qian, L., Yang, X., Ou, C., Lin, W., Gong, Z., Zhou, J., Xu, Z."CFHR1 is a potentially downregulated gene in lung adenocarcinoma". Molecular Medicine Reports 20, no. 4 (2019): 3642-3648. https://doi.org/10.3892/mmr.2019.10644