Breast Cancer Biomarker Discovery: Proteomics and Genomics Approaches

Akram Safaei--- ,
Mostafa Rezaei-Tavirani--- ,
Sara Sobhi--- ,
Mohammad Esmaeil Akbari---

Abstract


345

Abstract

Breast cancer is one of the major health problems of the Eastern world. Regardless of the survival rate improvement with progression in screening and adjuvant systemic therapies, still one – third of the patients with primary breast cancer have recurrence of micro metastasis after 10 years.  It is important to discover a reliable biomarker for detection of breast cancer. The underlying molecular mechanism of the disease needs to be better understood. Allied to genomics, proteomics technologies promise to be valuable for identifying new markers that improve screening, early diagnosis, prognosis and prediction of therapeutic response or toxicity, as well as the identification of new therapeutic targets. In this review, we present proteomic and genomic sciences have been used for differential analysis of breast cancer to find molecular changes of cancer for detection candidate biomarkers.

Keywords: Breast cancer; Biological Markers; Proteomics; Genomics

1.         Drake RR, Cazares LH, Jones EE, Fuller TW, Semmes OJ, Laronga C. Challenges to developing proteomic-based breast cancer diagnostics. OMICS: A Journal of Integrative Biology. 2011;15(5):251-9.

2.         Ugnat A, Xie L, Morriss J, Semenciw R, Mao Y. Survival of women with breast cancer in Ottawa, Canada: variation with age, stage, histology, grade and treatment. British journal of cancer. 2004;90(6):1138-43.

3.         Li CI. Discovery and Validation of Breast Cancer Early Detection Biomarkers in Preclinical Samples. Hormones and Cancer. 2011;2(2):125-31.

4.         Issaq HJ, Blonder J. Electrophoresis and liquid chromatography/tandem mass spectrometry in disease biomarker discovery. Journal of Chromatography B. 2009;877(13):1222-8.

5.         Kumar S, Mohan A, Guleria R. Biomarkers in cancer screening, research and detection: present and future: a review. Biomarkers. 2006;11(5):385-405.

6.         Cheang MCU, van de Rijn M, Nielsen TO. Gene expression profiling of breast cancer. Annu Rev pathmechdis Mech Dis. 2008;3:67-97.

7.         Morris SR, Carey LA. Gene expression profiling in breast cancer. Current opinion in oncology. 2007;19(6):547.

8.         Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. New England Journal of Medicine. 2009;360(8):790-800.

9.         Kim SY, Hahn WC. Cancer genomics: integrating form and function. Carcinogenesis. 2007;28(7):1387-92.

10.       Gast MCW, Schellens JHM, Beijnen JH. Clinical proteomics in breast cancer: a review. Breast cancer research and treatment. 2009;116(1):17-29.

11.       Davis M, Hanash S. High-throughput genomic technology in research and clinical management of breast cancer. Plasma-based proteomics in early detection and therapy. Breast Cancer Research. 2006;8(6):217.

12.       Drukier AK, Ossetrova N, Schors E, Krasik G, Grigoriev I, Koenig C, et al. High-sensitivity blood-based detection of breast cancer by multi photon detection diagnostic proteomics. Journal of proteome research. 2006;5(8):1906-15.

13.       Anderson KS, Ramachandran N, Wong J, Raphael JV, Hainsworth E, Demirkan G, et al. Application of protein microarrays for multiplexed detection of antibodies to tumor antigens in breast cancer. Journal of proteome research. 2008;7(4):1490-9.

14.       Lönneborg A, Aarøe J, Dumeaux V, Børresen-Dale AL. Found in transcription: gene expression and other novel blood biomarkers for the early detection of breast cancer. Expert review of anticancer therapy. 2009;9(8):1115-23.

15.       Brown NM, Stenzel TT, Friedman PN, Henslee J, Huper G, Marks JR. Evaluation of expression based markers for the detection of breast cancer cells. Breast cancer research and treatment. 2006;97(1):41-7.

16.       Alessandro G, Michele I, Paride P, Namshin K, Giulia S, Larry C, et al. A transcriptional sketch of a primary human breast cancer by 454 deep sequencing. BMC Genomics. 2009;10.

17.       Aaroe J, Lindahl T, Dumeaux V, Saebo S, Tobin D, Hagen N, et al. Gene expression profiling of peripheral blood cells for early detection of breast cancer. Breast Cancer Res. 2010;12(1):R7.

18.       Melnikov AA, Scholtens DM, Wiley EL, Khan SA, Levenson VV. Array-based multiplex analysis of DNA methylation in breast cancer tissues. The Journal of molecular diagnostics: JMD. 2008;10(1):93.

19.       Martens JWM, Margossian AL, Schmitt M, Foekens J, Harbeck N. DNA methylation as a biomarker in breast cancer. Future Oncology. 2009;5(8):1245-56.

20.       Grogan RH, Mitmaker EJ, Clark OH. The evolution of biomarkers in thyroid cancer—from mass screening to a personalized biosignature. Cancers. 2010;2(2):885-912.

21.       Hoheisel JD. Microarray technology: beyond transcript profiling and genotype analysis. Nature reviews genetics. 2006;7(3):200-10.

22.       Ellsworth DL, Ellsworth RE, Liebman MN, Hooke JA, Shriver CD. Genomic instability in histologically normal breast tissues: implications for carcinogenesis. The lancet oncology. 2004;5(12):753-8.

23.       Zhang B, Beeghly-Fadiel A, Long J, Zheng W. Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. The lancet oncology. 2011;12(5):477-88.

24.       Yu KD, Di GH, Fan L, Chen AX, Yang C, Shao ZM. Lack of an association between a functional polymorphism in the interleukin-6 gene promoter and breast cancer risk: a meta-analysis involving 25,703 subjects. Breast cancer research and treatment. 2010;122(2):483-8.

25.       Ayoub N, Lucas C, Kaddoumi A. Genomics and pharmacogenomics of breast cancer: current knowledge and trends. Asian Pacific Journal of Cancer Prevention. 2011;12:1127-40.

26.       Cherbal F, Salhi N, Bakour R, Adane S, Boualga K, Maillet P. BRCA1 and BRCA2 unclassified variants and missense polymorphisms in Algerian breast/ovarian cancer families. Disease Markers. 2012;32(6):343-53.

27.       Machackova E, Foretova L, Lukesova M, Vasickova P, Navratilova M, Coene I, et al. Spectrum and characterisation of BRCA1 and BRCA2 deleterious mutations in high-risk Czech patients with breast and/or ovarian cancer. BMC cancer. 2008;8(1):140.

28.       Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, et al. Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nature Genetics. 2006;38(11):1239-41.

29.       Weischer M, Bojesen SE, Tybjærg-Hansen A, Axelsson CK, Nordestgaard BG. Increased risk of breast cancer associated with CHEK2* 1100delC. Journal of clinical oncology. 2007;25(1):57-63.

30.       FitzGerald MG, MacDonald DJ, Krainer M, Hoover I, O'Neil E, Unsal H, et al. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. New England Journal of Medicine. 1996;334(3):143-9.

31.       Masciari S, Dillon DA, Rath M, Robson M, Weitzel JN, Balmana J, et al. Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort. Breast cancer research and treatment. 2012;133(3):1125-30.

32.       Hudelist G, Singer CF, Pischinger KID, Kaserer K, Manavi M, Kubista E, et al. Proteomic analysis in human breast cancer: identification of a characteristic protein expression profile of malignant breast epithelium. Proteomics. 2006;6(6):1989-2002.

33.       Habermann JK, Doering J, Hautaniemi S, Roblick UJ, Bündgen NK, Nicorici D, et al. The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome. International Journal of Cancer. 2009;124(7):1552-64.

34.       Kwei KA, Kung Y, Salari K, Holcomb IN, Pollack JR. Genomic instability in breast cancer: pathogenesis and clinical implications. Molecular oncology. 2010;4(3):255-66.

35.       Chistiakov DA, Hellemans B, Volckaert FAM. Microsatellites and their genomic distribution, evolution, function and applications: A review with special reference to fish genetics. Aquaculture. 2006;255(1):1-29.

36.       Janatova M, Pohlreich P. Microsatellite markers in breast cancer studies. Prague Medical Report. 2004;105(2):111-8.

37.       Siah SP, Quinn DM, Bennett GD, Casey G, Flower RLP, Suthers G, et al. Microsatellite instability markers in breast cancer: a review and study showing MSI was not detected at ‘BAT 25’and ‘BAT 26’microsatellite markers in early-onset breast cancer. Breast cancer research and treatment. 2000;60(2):135-42.

38.       Okada S, Tokunaga E, Kitao H, Akiyoshi S, Yamashita N, Saeki H, et al. Loss of heterozygosity at BRCA1 locus is significantly associated with aggressiveness and poor prognosis in breast cancer. Annals of surgical oncology. 2012:1-9.

39.       Callahan R, Cropp C, Merlo GR, Diella F, Venesio T, Lidereau R, et al. Genetic and molecular heterogeneity of breast cancer cells. Clinica chimica acta. 1993;217(1):63-73.

40.       Nowacka-Zawisza M, Bryś M, Romanowicz-Makowska H, Kulig A, Krajewska WM. Genetic instability in the RAD51 and BRCA1 regions in breast cancer. Cellular & molecular biology letters. 2007;12(2):192-205.

41.       Silva Soares EW, de Lima Santos SC, Bueno AG, Cavalli IJ, Cavalli LR, Fouto Matias JE, et al. Concomitant loss of heterozygosity at the< i> BRCA1</i> and< i> FHIT</i> genes as a prognostic factor in sporadic breast cancer. Cancer Genetics and Cytogenetics. 2010;199(1):24-30.

42.       Roncuzzi L, Brognara I, Baiocchi D, Amadori D, Gasperi-Campani A. Loss of heterozygosity at 17p13. 3-ter, distal to TP53, correlates with negative hormonal phenotype in sporadic breast cancer. Oncology reports. 2005;14(2):471-4.

43.       Cleton-Jansen AM. E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer? Breast Cancer Research. 2002;4(1):5-8.

44.       Pandis N, Bardi G, Mitelman F, Helm S. Deletion of the short arm of chromosome 3 in breast tumors. Genes, Chromosomes and Cancer. 1997;18(4):241-5.

45.       Tokunaga E, Okada S, Yamashita N, Akiyoshi S, Kitao H, Morita M, et al. High incidence and frequency of LOH are associated with aggressive features of high-grade HER2 and triple-negative breast cancers. Breast Cancer. 2012:1-9.

46.       Nowacka-Zawisza M, Brys M, Romanowicz-Makowska H, Zadrozny M, Kulig A, Krajewska WM. Loss of heterozygosity and microsatellite instability at RAD52 and RAD54 loci in breast cancer. Polish Journal of Pathology. 2006;57(2):83-9.

47.       Cheung A, Deng W. Telomere dysfunction, genome instability and cancer. Frontiers in bioscience: a journal and virtual library. 2008;13:2075.

48.       Fukino K, Shen L, Patocs A, Mutter GL, Eng C. Genomic instability within tumor stroma and clinicopathological characteristics of sporadic primary invasive breast carcinoma. JAMA: the journal of the American Medical Association. 2007;297(19):2103-11.

49.       Martinez-Delgado B, Yanowsky K, Inglada-Perez L, de la Hoya M, Caldes T, Vega A, et al. Shorter telomere length is associated with increased ovarian cancer risk in both familial and sporadic cases. Journal of medical genetics. 2012;49(5):341-4.

50.       Griffith JK, Bryant JE, Fordyce CA, Gilliland FD, Joste NE, Moyzis RK. Reduced telomere DNA content is correlated with genomic instability and metastasis in invasive human breast carcinoma. Breast cancer research and treatment. 1999;54(1):59-64.

51.       Zheng YL, Zhou X, Loffredo CA, Shields PG, Sun B. Telomere deficiencies on chromosomes 9p, 15p, 15q and Xp: potential biomarkers for breast cancer risk. Human molecular genetics. 2011;20(2):378-86.

52.       Martinez-Delgado B, Yanowsky K, Inglada-Perez L, Domingo S, Urioste M, Osorio A, et al. Genetic anticipation is associated with telomere shortening in hereditary breast cancer. PLoS genetics. 2011;7(7):e1002182.

53.       Meeker AK, Argani P. Telomere shortening occurs early during breast tumorigenesis: a cause of chromosome destabilization underlying malignant transformation? Journal of mammary gland biology and neoplasia. 2004;9(3):285-96.

54.       Bisoffi M, Heaphy CM, Griffith JK. Telomeres: prognostic markers for solid tumors. International Journal of Cancer. 2006;119(10):2255-60.

55.       Brooks JD, Cairns P, Shore RE, Klein CB, Wirgin I, Afanasyeva Y, et al. DNA methylation in pre-diagnostic serum samples of breast cancer cases: Results of a nested case–control study. Cancer epidemiology. 2010;34(6):717-23.

56.       Huang Y, Nayak S, Jankowitz R, Davidson NE, Oesterreich S. Epigenetics in breast cancer: what’s new. Breast Cancer Res. 2011;13(6):225.

57.       Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31(1):27-36.

58.       Suijkerbuijk K, Van Diest P, Van der Wall E. Improving early breast cancer detection: focus on methylation. Annals of Oncology. 2011;22(1):24-9.

59.       Dumitrescu RG. Epigenetic markers of early tumor development. Methods in molecular biology (Clifton, NJ). 2012;863:3.

60.       Wang W, Srivastava S. Strategic approach to validating methylated genes as biomarkers for breast cancer. Cancer Prevention Research. 2010;3(1):16-24.

61.       Ordway JM, Budiman MA, Korshunova Y, Maloney RK, Bedell JA, Citek RW, et al. Identification of novel high-frequency DNA methylation changes in breast cancer. PLoS One. 2007;2(12):e1314.

62.       Tommasi S, Karm DL, Wu X, Yen Y, Pfeifer GP. Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer. Breast Cancer Res. 2009;11(1):R14.

63.       Ting AH, McGarvey KM, Baylin SB. The cancer epigenome—components and functional correlates. Genes & development. 2006;20(23):3215-31.

64.       Pennings S, Allan J, Davey CS. DNA methylation, nucleosome formation and positioning. Briefings in functional genomics & proteomics. 2005;3(4):351-61.

65.       Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128(4):683-92.

66.       Stearns V, Zhou Q, Davidson NE. Epigenetic regulation as a new target for breast cancer therapy. Cancer investigation. 2007;25(8):659.

67.       Choe MK, Hong CP, Park J, Seo SH, Roh TY. Functional elements demarcated by histone modifications in breast cancer cells. Biochemical and Biophysical Research Communications. 2012.

68.       Stratmann A, Haendler B. Histone demethylation and steroid receptor function in cancer. Molecular and cellular endocrinology. 2011.

69.       Hung KE, Yu KH. Proteomic approaches to cancer biomarkers. Gastroenterology. 2010;138(1):46.

70.       Srivastava S, Srivastava RG. Proteomics in the forefront of cancer biomarker discovery. Journal of proteome research. 2005;4(4):1098-103.

71.       Gillette MA, Mani D, Carr SA. Place of pattern in proteomic biomarker discovery. Journal of proteome research. 2005;4(4):1143-54.

72.       Baselga J. Treatment of HER2-overexpressing breast cancer. Annals of Oncology. 2010;21(suppl 7):vii36-vii40.

73.       Leppä S, Saarto T, Vehmanen L, Blomqvist C, Elomaa I. A high serum matrix metalloproteinase-2 level is associated with an adverse prognosis in node-positive breast carcinoma. Clinical cancer research. 2004;10(3):1057-63.

74.       El Yazidi-Belkoura I, Adriaenssens E, Vercoutter-Edouart A, Lemoine J, Nurcombe V, Hondermarck H. Proteomics of breast cancer: outcomes and prospects. Technology in cancer research & treatment. 2002;1(4):287.

75.       Qin XJ, Ling BX. Proteomic studies in breast cancer (Review). Oncology Letters. 2012;3(4):735.

76.       Moreira JMA, Ohlsson G, Rank FE, Celis JE. Down-regulation of the tumor suppressor protein 14-3-3σ is a sporadic event in cancer of the breast. Molecular & Cellular Proteomics. 2005;4(4):555-69.

77.       Zurita M, Lara P, Del Moral R, Torres B, Linares-Fernández J, Arrabal S, et al. Hypermethylated 14-3-3-σ and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis. BMC cancer. 2010;10(1):217.

78.       Schultz J, Ibrahim SM, Vera J, Kunz M. 14-3-3σ gene silencing during melanoma progression and its role in cell cycle control and cellular senescence. Molecular cancer. 2009;8(1):53.

79.       Mathelin C, Cromer A, Wendling C, Tomasetto C, Rio MC. Serum biomarkers for detection of breast cancers: a prospective study. Breast cancer research and treatment. 2006;96(1):83-90.

80.       Sanders ME, Dias EC, Xu BJ, Mobley JA, Billheimer D, Roder H, et al. Differentiating proteomic biomarkers in breast cancer by laser capture microdissection and MALDI MS. Journal of proteome research. 2008;7(4):1500-7.

81.       Bhargava R, Beriwal S, McManus K, Dabbs DJ. CK5 is more sensitive than CK5/6 in identifying the “basal-like” phenotype of breast carcinoma. American journal of clinical pathology. 2008;130(5):724-30.

82.       Waligórska-Stachura J, Jankowska A, Waśko R, Liebert W, Biczysko M, Czarnywojtek A, et al. Survivin--prognostic tumor biomarker in human neoplasms--review. Ginekologia polska. 2012;83(7):537.

83.       Liu Y, Zhao J, Zhang PY, Zhang Y, Sun SY, Yu SY, et al. MicroRNA-10b targets E-cadherin and modulates breast cancer metastasis. Medical science monitor: international medical journal of experimental and clinical research. 2012;18(8):BR299.

84.       Li J, Zhang Z, Rosenzweig J, Wang YY, Chan DW. Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clinical chemistry. 2002;48(8):1296-304.

85.       Lim YP. Mining the tumor phosphoproteome for cancer markers. Clinical cancer research. 2005;11(9):3163-9.

86.       Gamagedara S, Ma Y. Biomarker analysis for prostate cancer diagnosis using LC-MS and CE-MS. Bioanalysis. 2011;3(18):2129-42.

87.       Whelan SA, Lu M, He J, Yan W, Saxton RE, Faull KF, et al. Mass spectrometry (LC-MS/MS) site-mapping of N-glycosylated membrane proteins for breast cancer biomarkers. J Proteome Res. 2009;8(8):4151-60.

88.       Song J, Patel M, Rosenzweig CN, Chan-Li Y, Sokoll LJ, Fung ET, et al. Quantification of fragments of human serum inter-alpha-trypsin inhibitor heavy chain 4 by a surface-enhanced laser desorption/ionization-based immunoassay. Clin Chem. 2006;52(6):1045-53.

89.       Graves PR, Haystead TAJ. Molecular biologist's guide to proteomics. Microbiology and Molecular Biology Reviews. 2002;66(1):39-63.

90.       Kang UB, Ahn Y, Lee JW, Kim YH, Kim J, Yu MH, et al. Differential profiling of breast cancer plasma proteome by isotope-coded affinity tagging method reveals biotinidase as a breast cancer biomarker. BMC Cancer. 2010;10:114.

91.       Ueda M, Misumi Y, Mizuguchi M, Nakamura M, Yamashita T, Sekijima Y, et al. SELDI-TOF mass spectrometry evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy. Clinical chemistry. 2009;55(6):1223-7.

92.       Lebrecht A, Boehm D, Schmidt M, Koelbl H, Grus FH. Surface-enhanced Laser Desorption/Ionisation Time-of-flight Mass Spectrometry to Detect Breast Cancer Markers in Tears and Serum. Cancer Genomics Proteomics. 2009;6(2):75-83.


Full Text:

PDF

367