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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Longitudinal autoantibody responses against tumor-associated antigens decrease in breast cancer patients according to treatment modality

Authors: Rick L. Evans, James V. Pottala, Satoshi Nagata, Kristi A. Egland

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Metastatic breast cancer (BCa) is most often diagnosed months after completion of treatment of the primary tumor when a patient reports physical symptoms. Besides a physical examination, no other alternative recurrence screening method is recommended for routine follow-up care. Detection of autoantibodies against tumor-associated antigens (TAAs) has demonstrated promise for distinguishing healthy women from patients diagnosed with primary BCa. However, it is unknown what changes occur to patient autoantibody levels during and after treatment.

Methods

Three serial blood draws were collected from 200 BCa patients: before treatment, 6 and 12 months after surgery. Patients were categorized according to treatment regimen, including surgery, chemotherapy, radiation, trastuzumab and hormonal therapies. The longitudinal samples were assayed for autoantibody responses against 32 conformation-carrying TAAs using a Luminex multiplex bead assay.

Results

The treatment modality groups that had the greatest decrease in autoantibody response levels were radiation + hormonal therapy; radiation + chemotherapy; and radiation + hormonal therapy + chemotherapy. For these three treatment groups, autoantibody responses against 9 TAAs (A1AT, ANGPTL4, CAPC, CST2, DKK1, GFRA1, GRN, LGALS3 and LRP10) were significantly reduced at 12 months after surgery compared to before treatment. One TAA, GRP78, had a significantly increased autoantibody response after 12 months.

Conclusions

Single treatment regimens alone did not significantly alter autoantibodies levels against the studied TAAs. Radiation treatment was the common denominator of the three most affected groups for significant changes in autoantibody response levels.
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Literature
1.
Aragon R, Morgan J, Wong JH, Lum S. Potential impact of USPSTF recommendations on early diagnosis of breast cancer. Ann Surg Oncol. 2011;18(11):3137–42.CrossRefPubMed
2.
Kontos M, Roy P, Rizos D, Petrou A, Hamed H. Contralateral relapse after surgery for breast cancer: evaluation of follow-up paradigms. Int J Clin Pract. 2013;67(11):1113–7.CrossRefPubMed
3.
Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220–41.CrossRefPubMed
4.
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, et al. SEER Cancer Statistics Review, 1975–2012, National Cancer Institute. Bethesda: based on November 2014 SEER data submission, posted to the SEER web site, http://​seer.​cancer.​gov/​csr/​1975_​2012, April 2015.
5.
6.
Dawood S, Broglio K, Gonzalez-Angulo AM, Buzdar AU, Hortobagyi GN, Giordano SH. Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol. 2008;26(30):4891–8.CrossRefPubMedPubMedCentral
7.
Lu J, Steeg PS, Price JE, Krishnamurthy S, Mani SA, Reuben J, Cristofanilli M, Dontu G, Bidaut L, Valero V, et al. Breast cancer metastasis: challenges and opportunities. Cancer Res. 2009;69(12):4951–3.CrossRefPubMed
8.
Kimbung S, Loman N, Hedenfalk I. Clinical and molecular complexity of breast cancer metastases. Semin Cancer Biol. 2015;35:85–95.CrossRefPubMed
9.
Cardoso F, Costa A, Norton L, Cameron D, Cufer T, Fallowfield L, Francis P, Gligorov J, Kyriakides S, Lin N, et al. 1st international consensus guidelines for advanced breast cancer (ABC 1). Breast. 2012;21(3):242–52.CrossRefPubMed
10.
Schneble EJ, Graham LJ, Shupe MP, Flynt FL, Banks KP, Kirkpatrick AD, Nissan A, Henry L, Stojadinovic A, Shumway NM, et al. Current approaches and challenges in early detection of breast cancer recurrence. J Cancer. 2014;5(4):281–90.CrossRefPubMedPubMedCentral
11.
Lu WL, Jansen L, Post WJ, Bonnema J, Van de Velde JC, De Bock GH. Impact on survival of early detection of isolated breast recurrences after the primary treatment for breast cancer: a meta-analysis. Breast Cancer Res Treat. 2009;114(3):403–12.CrossRefPubMed
12.
Chapman C, Murray A, Chakrabarti J, Thorpe A, Woolston C, Sahin U, Barnes A, Robertson J. Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol. 2007;18(5):868–73.CrossRefPubMed
13.
Lacombe J, Mange A, Solassol J. Use of autoantibodies to detect the onset of breast cancer. J Immunol Res. 2014;2014(Article ID 574981):574988.
14.
Henry NL, Hayes DF, Ramsey SD, Hortobagyi GN, Barlow WE, Gralow JR. Promoting quality and evidence-based care in early-stage breast cancer follow-up. J Natl Cancer Inst. 2014;106(4):dju034.CrossRefPubMedPubMedCentral
15.
Egland KA, Vincent JJ, Strausberg R, Lee B, Pastan I. Discovery of the breast cancer gene BASE using a molecular approach to enrich for genes encoding membrane and secreted proteins. Proc Natl Acad Sci U S A. 2003;100(3):1099–104.CrossRefPubMedPubMedCentral
16.
Evans RL, Pottala JV, Egland KA. Classifying patients for breast cancer by detection of autoantibodies against a panel of conformation-carrying antigens. Cancer Prev Res. 2014;7(5):545–55.CrossRef
17.
Carson RT, Vignali DA. Simultaneous quantitation of 15 cytokines using a multiplexed flow cytometric assay. J Immunol Methods. 1999;227(1–2):41–52.CrossRefPubMed
18.
Egland KA, Liu XF, Squires S, Nagata S, Man YG, Bera TK, Onda M, Vincent JJ, Strausberg RL, Lee B, et al. High expression of a cytokeratin-associated protein in many cancers. Proc Natl Acad Sci U S A. 2006;103(15):5929–34.CrossRefPubMedPubMedCentral
19.
Fossa A, Alsoe L, Crameri R, Funderud S, Gaudernack G, Smeland EB. Serological cloning of cancer/testis antigens expressed in prostate cancer using cDNA phage surface display. Cancer Immunol Immunother. 2004;53(5):431–8.CrossRefPubMed
20.
Gonzalez-Gronow M, Cuchacovich M, Llanos C, Urzua C, Gawdi G, Pizzo SV. Prostate cancer cell proliferation in vitro is modulated by antibodies against glucose-regulated protein 78 isolated from patient serum. Cancer Res. 2006;66(23):11424–31.CrossRefPubMed
21.
Liu W, De La Torre IG, Gutierrez-Rivera MC, Wang B, Liu Y, Dai L, Qian W, Zhang JY. Detection of autoantibodies to multiple tumor-associated antigens (TAAs) in the immunodiagnosis of breast cancer. Tumour Biol. 2015;36(2):1307–12.CrossRefPubMed
22.
Lopez-Arias E, Aguilar-Lemarroy A, Felipe Jave-Suarez L, Morgan-Villela G, Mariscal-Ramirez I, Martinez-Velazquez M, Alvarez AH, Gutierrez-Ortega A, Hernandez-Gutierrez R. Alpha 1-antitrypsin: a novel tumor-associated antigen identified in patients with early-stage breast cancer. Electrophoresis. 2012;33(14):2130–7.CrossRefPubMed
23.
O'Rourke DJ, DiJohnson DA, Caiazzo RJ Jr, Nelson JC, Ure D, O'Leary MP, Richie JP, Liu BC. Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen. Clin Chim Act. 2012;413(5–6):561–7.CrossRef
24.
Xie C, Kim HJ, Haw JG, Kalbasi A, Gardner BK, Li G, Rao J, Chia D, Liong M, Punzalan RR, et al. A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases. J Transl Med. 2011;9:43.CrossRefPubMedPubMedCentral
25.
Xu Y, Jin Y, Liu L, Zhang X, Chen Y, Wei J. Study of circulating IgG antibodies to peptide antigens derived from BIRC5 and MYC in cervical cancer. FEBS Open Bio. 2015;5:198–201.CrossRefPubMedPubMedCentral
26.
Yang Z, Chevolot Y, Gehin T, Solassol J, Mange A, Souteyrand E, Laurenceau E. Improvement of protein immobilization for the elaboration of tumor-associated antigen microarrays: application to the sensitive and specific detection of tumor markers from breast cancer sera. Biosens Bioelectron. 2013;40(1):385–92.CrossRefPubMed
27.
Ye H, Sun C, Ren P, Dai L, Peng B, Wang K, Qian W, Zhang J. Mini-array of multiple tumor-associated antigens (TAAs) in the immunodiagnosis of breast cancer. Oncol Lett. 2013;5(2):663–8.CrossRefPubMed
28.
Zhou SL, Yue WB, Fan ZM, Du F, Liu BC, Li B, Han XN, Ku JW, Zhao XK, Zhang P, et al. Autoantibody detection to tumor-associated antigens of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn, and Koc for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma. Dis Esophagus. 2014;27(8):790–7.CrossRefPubMed
29.
Zuo X, Chen L, Liu L, Zhang Z, Zhang X, Yu Q, Feng L, Zhao X, Qin T. Identification of a panel of complex autoantigens (LGALS3, PHB2, MUC1, and GK2) in combination with CA15-3 for the diagnosis of early-stage breast cancer. Tumour Biol. 2015;37(1):1309–17.CrossRefPubMed
30.
31.
32.
Liu W, Peng B, Lu Y, Xu W, Qian W, Zhang JY. Autoantibodies to tumor-associated antigens as biomarkers in cancer immunodiagnosis. Autoimmun Rev. 2011;10(6):331–5.CrossRefPubMed
33.
Zhu Q, Liu M, Dai L, Ying X, Ye H, Zhou Y, Han S, Zhang JY. Using immunoproteomics to identify tumor-associated antigens (TAAs) as biomarkers in cancer immunodiagnosis. Autoimmun Rev. 2013;12(12):1123–8.CrossRefPubMedPubMedCentral
34.
35.
Lu H, Goodell V, Disis ML. Humoral immunity directed against tumor-associated antigens as potential biomarkers for the early diagnosis of cancer. J Proteome Res. 2008;7(4):1388–94.CrossRefPubMed
36.
Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature. 2003;421(6924):756–60.CrossRefPubMed
37.
Garrett JT, Rawale S, Allen SD, Phillips G, Forni G, Morris JC, Kaumaya PT. Novel engineered trastuzumab conformational epitopes demonstrate in vitro and in vivo antitumor properties against HER-2/neu. J Immunol. 2007;178(11):7120–31.CrossRefPubMed
38.
Haas IG. BiP (GRP78), an essential hsp70 resident protein in the endoplasmic reticulum. Experientia. 1994;50(11–12):1012–20.CrossRefPubMed
39.
Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res. 2007;67(8):3496–9.CrossRefPubMed
40.
Luo B, Lee AS. The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies. Oncogene. 2013;32(7):805–18.CrossRefPubMed
41.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRefPubMed
42.
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003;100(14):8418–23.CrossRefPubMedPubMedCentral
Metadata
Title
Longitudinal autoantibody responses against tumor-associated antigens decrease in breast cancer patients according to treatment modality
Authors
Rick L. Evans
James V. Pottala
Satoshi Nagata
Kristi A. Egland
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4022-5

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