Skip to main content

Advertisement

Log in

Clinicopathological significance and prognostic value of Xeroderma pigmentosum complementary group C (XPC) expression in sporadic breast cancer patients

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Breast cancer is the most common type of cancer among women worldwide, and the incidence of breast cancer is increasing in the developing world. Estrogen exposure is a major risk factor for breast cancer, and estrogen oxidative metabolites have been implicated in chemical carcinogenesis. Xeroderma pigmentosum complementary group C (XPC) plays an important and multifaceted role in cell protection from oxidative DNA damage. Thus, XPC inactivation may be involved in the early stage of breast cancer. The aim of this study was to investigate the expression of XPC protein in sporadic breast cancer tissues and determine whether XPC expression influences breast cancer malignancy and clinical outcome. Fifteen cases of adjacent non-tumor breast tissue, 28 cases of fibroadenomas and 235 cases of breast carcinomas were examined by immunohistochemistry using polyclonal antibody to XPC. Both cytoplasmic and nuclear expression level of XPC were downregulated in breast carcinoma when compared to non-tumor tissues (P < 0.05). The nuclear expression level of XPC was significantly associated with expression of BCL2 (r = 0.231, P = 0.033) and p53 (r = 0.205, P = 0.011), and nuclear expression of XPC was significantly associated with patients’ age (P = 0.024). Neither cytoplasmic nor nuclear expression level of XPC had impact on patients’ survival in the whole samples. However, XPC expression was correlated with adverse survival in HER2-positive, but not HER2-negative, tumors, as demonstrated by Kaplan–Meier analysis. Our results suggested that the XPC protein is involved in the occurrence and progression of breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19(8):1893–907.

    Article  PubMed  Google Scholar 

  2. Song M, Lee KM, Kang D. Breast cancer prevention based on gene-environment interaction. Mol Carcinog. 2011;50(4):280–90.

    Article  PubMed  CAS  Google Scholar 

  3. Henderson BE, Ross R, Bernstein L. Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res. 1988;48(2):246–53.

    PubMed  CAS  Google Scholar 

  4. Bolton JL, Thatcher GR. Potential mechanisms of estrogen quinone carcinogenesis. Chem Res Toxicol. 2008;21(1):93–101.

    Article  PubMed  Google Scholar 

  5. Rajapakse N, Butterworth M, Kortenkamp A. Detection of DNA strand breaks and oxidized DNA bases at the single-cell level resulting from exposure to estradiol and hydroxylated metabolites. Environ Mol Mutagen. 2005;45(4):397–404.

    Article  PubMed  CAS  Google Scholar 

  6. Charames GS, Bapat B. Genomic instability and cancer. Curr Mol Med. 2003;3(7):589–96.

    Article  PubMed  CAS  Google Scholar 

  7. Kim IJ, Ku JL, Kang HC, Park JH, Yoon KA, Shin Y, et al. Mutational analysis of OGG1, MYH, MTH1 in FAP, HNPCC and sporadic colorectal cancer patients: R154H OGG1 polymorphism is associated with sporadic colorectal cancer patients. Hum Genet. 2004;115(6):498–503.

    Article  PubMed  CAS  Google Scholar 

  8. Kuraoka I, Bender C, Romieu A, Cadet J, Wood RD, Lindahl T. Removal of oxygen free-radical-induced 5’, 8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells. Proc Natl Acad Sci USA. 2000;97(8):3832–7.

    Article  PubMed  CAS  Google Scholar 

  9. Kovacs E, Stucki D, Weber W, Muller H. Impaired DNA-repair synthesis in lymphocytes of breast cancer patients. Eur J Cancer Clin Oncol. 1986;22(7):863–9.

    Article  PubMed  CAS  Google Scholar 

  10. Ramos JM, Ruiz A, Colen R, Lopez ID, Grossman L, Matta JL. DNA repair and breast carcinoma susceptibility in women. Cancer. 2004;100(7):1352–7.

    Article  PubMed  CAS  Google Scholar 

  11. Latimer JJ, Johnson JM, Kelly CM, Miles TD, Beaudry-Rodgers KA, Lalanne NA, et al. Nucleotide excision repair deficiency is intrinsic in sporadic stage I breast cancer. Proc Natl Acad Sci USA. 2010;107(50):21725–30.

    Article  PubMed  CAS  Google Scholar 

  12. Hey T, Lipps G, Sugasawa K, Iwai S, Hanaoka F, Krauss G. The XPC-HR23B complex displays high affinity and specificity for damaged DNA in a true-equilibrium fluorescence assay. Biochemistry. 2002;41(21):6583–7.

    Article  PubMed  CAS  Google Scholar 

  13. Yang A, Miron S, Mouawad L, Duchambon P, Blouquit Y, Craescu CT. Flexibility and plasticity of human centrin 2 binding to the xeroderma pigmentosum group C protein (XPC) from nuclear excision repair. Biochemistry. 2006;45(11):3653–63.

    Article  PubMed  CAS  Google Scholar 

  14. Sugasawa K, Okamoto T, Shimizu Y, Masutani C, Iwai S, Hanaoka F. A multistep damage recognition mechanism for global genomic nucleotide excision repair. Genes Dev. 2001;15(5):507–21.

    Article  PubMed  CAS  Google Scholar 

  15. Sugasawa K, Shimizu Y, Iwai S, Hanaoka F. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2002;1(1):95–107.

    Article  CAS  Google Scholar 

  16. D’Errico M, Parlanti E, Teson M, de Jesus BM, Degan P, Calcagnile A, et al. New functions of XPC in the protection of human skin cells from oxidative damage. EMBO J. 2006;25(18):4305–15.

    Article  PubMed  Google Scholar 

  17. Shimizu Y, Iwai S, Hanaoka F, Sugasawa K. Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase. EMBO J. 2003;22(1):164–73.

    Article  PubMed  CAS  Google Scholar 

  18. Shore RE, Zeleniuch-Jacquotte A, Currie D, Mohrenweiser H, Afanasyeva Y, Koenig KL, et al. Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk. Int J Cancer. 2008;122(9):2101–5.

    Article  PubMed  CAS  Google Scholar 

  19. El-Deiry WS. Transactivation of repair genes by BRCA1. Cancer Biol Ther. 2002;1(5):490–1.

    PubMed  Google Scholar 

  20. Hartman AR, Ford JM. BRCA1 induces DNA damage recognition factors and enhances nucleotide excision repair. Nat Genet. 2002;32(1):180–4.

    Article  PubMed  CAS  Google Scholar 

  21. Yang J, Xu Z, Li J, Zhang R, Zhang G, Ji H, et al. XPC epigenetic silence coupled with p53 alteration has a significant impact on bladder cancer outcome. J Urol. 2010;184(1):336–43.

    Article  PubMed  CAS  Google Scholar 

  22. Chen Z, Yang J, Wang G, Song B, Li J, Xu Z. Attenuated expression of xeroderma pigmentosum group C is associated with critical events in human bladder cancer carcinogenesis and progression. Cancer Res. 2007;67(10):4578–85.

    Article  PubMed  CAS  Google Scholar 

  23. Wu YH, Cheng YW, Chang JT, Wu TC, Chen CY, Lee H. Reduced XPC messenger RNA level may predict a poor outcome of patients with nonsmall cell lung cancer. Cancer. 2007;110(1):215–23.

    Article  PubMed  Google Scholar 

  24. Fautrel A, Andrieux L, Musso O, Boudjema K, Guillouzo A, Langouet S. Overexpression of the two nucleotide excision repair genes ERCC1 and XPC in human hepatocellular carcinoma. J Hepatol. 2005;43(2):288–93.

    Article  PubMed  CAS  Google Scholar 

  25. Rezvani HR, Kim AL, Rossignol R, Ali N, Daly M, Mahfouf W, et al. XPC silencing in normal human keratinocytes triggers metabolic alterations that drive the formation of squamous cell carcinomas. J Clin Invest. 2011;121(1):195–211.

    Article  PubMed  CAS  Google Scholar 

  26. Wu YH, Tsai Chang JH, Cheng YW, Wu TC, Chen CY, Lee H. Xeroderma pigmentosum group C gene expression is predominantly regulated by promoter hypermethylation and contributes to p53 mutation in lung cancers. Oncogene. 2007;26(33):4761–73.

    Article  PubMed  CAS  Google Scholar 

  27. Xu XS, Wang L, Abrams J, Wang G. Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer. J Hematol Oncol. 2011;4:17. doi:10.1186/1756-8722-4-17.

    Article  PubMed  CAS  Google Scholar 

  28. Takebayashi Y, Nakayama K, Kanzaki A, Miyashita H, Ogura O, Mori S, et al. Loss of heterozygosity of nucleotide excision repair factors in sporadic ovarian, colon and lung carcinomas: implication for their roles of carcinogenesis in human solid tumors. Cancer Lett. 2001;174(2):115–25.

    Article  PubMed  CAS  Google Scholar 

  29. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75(5):855–62.

    Article  PubMed  CAS  Google Scholar 

  30. Hanova M, Stetina R, Vodickova L, Vaclavikova R, Hlavac P, Smerhovsky Z, et al. Modulation of DNA repair capacity and mRNA expression levels of XRCC1, hOGG1 and XPC genes in styrene-exposed workers. Toxicol Appl Pharmacol. 2010;248(3):194–200.

    Article  PubMed  CAS  Google Scholar 

  31. Sandrini JZ, Trindade GS, Nery LE, Marins LF. Time-course expression of DNA repair-related genes in hepatocytes of zebrafish (Danio rerio) after UV-B exposure. Photochem Photobiol. 2009;85(1):220–6.

    Article  PubMed  CAS  Google Scholar 

  32. Adimoolam S, Ford JM. p53 and DNA damage-inducible expression of the xeroderma pigmentosum group C gene. Proc Natl Acad Sci USA. 2002;99(20):12985–90.

    Article  PubMed  CAS  Google Scholar 

  33. Fitch ME, Cross IV, Ford JM. p53 responsive nucleotide excision repair gene products p48 and XPC, but not p53, localize to sites of UV-irradiation-induced DNA damage, in vivo. Carcinogenesis. 2003;24(5):843–50.

    Article  PubMed  CAS  Google Scholar 

  34. Wang G, Chuang L, Zhang X, Colton S, Dombkowski A, Reiners J, et al. The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated cell cycle regulation. Nucleic Acids Res. 2004;32(7):2231–40.

    Article  PubMed  CAS  Google Scholar 

  35. Wang G, Dombkowski A, Chuang L, Xu XX. The involvement of XPC protein in the cisplatin DNA damaging treatment-mediated cellular response. Cell Res. 2004;14(4):303–14.

    Article  PubMed  CAS  Google Scholar 

  36. Guillem VM, Cervantes F, Martinez J, Alvarez-Larran A, Collado M, Camos M, et al. XPC genetic polymorphisms correlate with the response to imatinib treatment in patients with chronic phase chronic myeloid leukemia. Am J Hematol. 2010;85(7):482–6.

    Article  PubMed  CAS  Google Scholar 

  37. Lai TC, Chow KC, Fang HY, Cho HC, Chen CY, Lin TY, et al. Expression of xeroderma pigmentosum complementation group C protein predicts cisplatin resistance in lung adenocarcinoma patients. Oncol Rep. 2011;25(5):1243–51.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are very grateful to Dr. Desheng Huang from the Department of Mathematics, College of Basic Medical Sciences, China Medical University for statistical analysis. This work was supported by grants from National Natural Science Foundation of China (No 30873097 and No 30973559), and this study was also supported by the science and technology department of Liao ning province (No 2010225001).

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Minjie Wei.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bai, X., Jin, F., Fu, Y. et al. Clinicopathological significance and prognostic value of Xeroderma pigmentosum complementary group C (XPC) expression in sporadic breast cancer patients. Med Oncol 29, 1543–1553 (2012). https://doi.org/10.1007/s12032-011-0086-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-0086-7

Keywords

Navigation