Top

Systematic Reviews

Published in:

Open Access 01-12-2022 | Breast Cancer | Research

Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis

Authors: Thejas Kathrikolly, Sreekumaran N. Nair, Aju Mathew, Prakash P. U. Saxena, Suma Nair

Published in: Systematic Reviews | Issue 1/2022

Abstract

Background

The increasing incidence of breast cancer necessitates the need to explore alternate screening strategies that circumvent the setbacks of conventional techniques especially among population that report earlier age at diagnosis. Serum autoantibodies is one such potential area of interest. However, their ubiquitous presence across cancer types limits its applicability to any one specific type of cancer. This review was therefore carried out to explore and consolidate available evidence on autoantibodies for early detection of breast cancer and to identify those that demonstrated a higher sensitivity.

Methods

A diagnostic test accuracy (DTA) review was carried out to ascertain serum autoantibodies that could be used for early detection of breast cancer among women. All relevant articles that investigated the role of autoantibodies in early detection of breast cancer were included for the review. MEDLINE, Scopus, ProQuest, Ovid SP, and Cochrane Library were searched extensively for eligible studies. Quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. RevMan 5.3 was used for exploratory and MetaDTA 2019 for hierarchical analyses. The review helped identify the most frequently investigated autoantibodies and a meta-analysis further consolidated the findings.

Results

A total of 53 articles were included for the final analysis that reported over a 100 autoantibodies that were studied for early detection of breast cancer in women. P53, MUC1, HER2, HSP60, P16, Cyclin B1, and c-Myc were the most frequently investigated autoantibodies. Of these P53, MUC1, HER2, and HSP60 exhibited higher summary sensitivity measures. While the individual pooled sensitivity estimates ranged between 10 and 56%, the panel sensitivity values reported across studies were higher with an estimated range of 60–87%.

Conclusion

Findings from the review indicate a higher sensitivity for an autoantibody panel in comparison to individual assays. A panel comprising of P53, MUC1, HER2, and HSP60 autoantibodies has the potential to be investigated as an early detection biomarker for breast cancer.

Available only for authorised users

Sung H, Ferlay J, Siegel RL, Laversanne M., Soerjomataram I, Jemal A. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021. https://doi.org/10.3322/caac.21660

Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol. 2017. https://doi.org/10.1111/ajco.12661.CrossRefPubMed

Chapman C, Murray A, Chakrabarti J, Thorpe A, Woolston C, Sahin U, et al. Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol. 2007. https://doi.org/10.1093/annonc/mdm007.CrossRefPubMed

Pedersen JW, Wandall HH. Autoantibodies as Biomarkers in Cancer. Lab Med. 2011. https://doi.org/10.1309/LM2T3OU3RZRTHKSN.CrossRef

Desmetz C, Bascoul-Mollevi C, Rochaix P, Lamy P-J, Kramar A, Rouanet P, et al. Identification of a new panel of serum autoantibodies associated with the presence of in situ carcinoma of the breast in younger women. Clin Cancer Res. 2009. https://doi.org/10.1158/1078-0432.CCR-08-3307.CrossRefPubMed

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement statement. Syst Rev. 2015. https://doi.org/10.1186/2046-4053-4-1.CrossRefPubMedPubMedCentral

Leeflang MMG. Systematic reviews and meta-analyses of diagnostic test accuracy. Clin Microbiol Infect. 2014. https://doi.org/10.1111/1469-0691.12474.CrossRefPubMed

Leeflang MMG, Deeks JJ, Gatsonis C, Bossuyt PMM, Cochrane Diagnostic Test Accuracy Working Group. Systematic reviews of diagnostic test accuracy. Ann Intern Med. 2008. https://doi.org/10.7326/0003-4819-149-12-200812160-00008.

Whiting PF, Rutjes AWS, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies. Ann Intern Med. 2011. https://doi.org/10.7326/0003-4819-155-8-201110180-00009.CrossRefPubMed

10.

Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

11.

Freeman SC, Kerby CR, Patel A, Cooper NJ, Quinn T, Sutton AJ. Development of an interactive web-based tool to conduct and interrogate meta-analysis of diagnostic test accuracy studies: MetaDTA. BMC Med Res Methodol. 2019. https://doi.org/10.1186/s12874-019-0724-x.CrossRefPubMedPubMedCentral

12.

Chen X, Dong K, Long M, Lin F, Wang X, Wei J, et al. Serum anti-AEG-1 auto-antibody is a potential novel biomarker for malignant tumors. Oncol Lett. 2012. https://doi.org/10.3892/ol.2012.734.CrossRefPubMedPubMedCentral

13.

Tomkiel JE, Alansari H, Tang N, Virgin JB, Yang X, VandeVord P, et al. Autoimmunity to the M(r) 32,000 subunit of replication protein A in breast cancer. Clin Cancer Res. 2002;8(3):752–8.PubMedPubMedCentral

14.

Wu M, Mao C, Chen Q, Cu XW, Zhang WS. Serum p53 protein and anti-p53 antibodies are associated with increased cancer risk: a case-control study of 569 patients and 879 healthy controls. Mol Biol Rep. 2010. https://doi.org/10.1007/s11033-009-9744-7.CrossRefPubMedPubMedCentral

15.

Angelopoulou K, Diamandis EP, Sutherland DJA, Kellen JA, Bunting PS. Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers. Int J Cancer. 1994. https://doi.org/10.1002/ijc.2910580404.CrossRefPubMed

16.

Nesterova MV, Johnson N, Cheadle C, Bates SE, Mani S, Stratakis CA, et al. Autoantibody cancer biomarker: extracellular protein kinase A. Cancer Res. 2006. https://doi.org/10.1158/0008-5472.CAN-06-1049.CrossRefPubMed

17.

Nunna V, Banerjee S, Kumar MK. Circulatory autoantibodies against hyaluronic acid binding proteins: a novel serum biomarker. Asian J Pharm Clin Res. 2014;7(2):199–203.

18.

Wandall HH, Blixt O, Tarp MA, Pedersen JW, Bennett EP, Mandel U, et al. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. Cancer Res. 2010. https://doi.org/10.1158/0008-5472.CAN-09-2893.CrossRefPubMedPubMedCentral

19.

Regele S, Kohlberger P, Vogl FD, Böhm W, Kreienberg R, Runnebaum IB. Serum p53 autoantibodies in patients with minimal lesions of ductal carcinoma in situ of the breast. Br J Cancer. 1999. https://doi.org/10.1038/sj.bjc.6690751.CrossRefPubMedPubMedCentral

20.

Bassaro L, Russell SJ, Pastwa E, Somiari SA, Somiari RI. Screening for multiple autoantibodies in plasma of patients with breast cancer. Cancer Genomics Proteomics. 2017. https://doi.org/10.21873/cgp.20052.CrossRefPubMedPubMedCentral

21.

Chen C, Huang Y, Zhang C, Liu T, Zheng H, Wan S, et al. Circulating antibodies to p16 protein-derived peptides in breast cancer. Mol Clin Oncol. 2015. https://doi.org/10.3892/mco.2015.485.CrossRefPubMedPubMedCentral

22.

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 (Phila). 2014. https://doi.org/10.1158/1940-6207.CAPR-13-0416.CrossRef

23.

Liu T, Song Y, Shi Q-Y, Liu Y, Bai X, Pang D. Study of circulating antibodies against CD25 and FOXP3 in breast cancer. Tumour Biol. 2014. https://doi.org/10.1007/s13277-013-1500-x.CrossRefPubMed

24.

Mohammed M, Abdelhafiz K. Autoantibodies in the sera of breast cancer patients: antinuclear and anti-double stranded DNA antibodies as example. J Cancer Res Ther. 2015. https://doi.org/10.4103/0973-1482.157314.CrossRefPubMed

25.

Wang J, Figueroa JD, Wallstrom G, Barker K, Park JG, Demirkan G, et al. Plasma Autoantibodies Associated with Basal-like Breast Cancers. Cancer Epidemiol Biomarkers Prev. 2015. https://doi.org/10.1158/1055-9965.EPI-15-0047.CrossRefPubMedPubMedCentral

26.

Yahalom G, Weiss D, Novikov I, Bevers TB, Radvanyi LG, Liu M, et al. An Antibody-based Blood Test Utilizing a Panel of Biomarkers as a New Method for Improved Breast Cancer Diagnosis. Biomark Cancer. 2013. https://doi.org/10.4137/BIC.S13236.CrossRefPubMedPubMedCentral

27.

Yi JK, Chang JW, Han W, Lee JW, Ko E, Kim DH, et al. Autoantibody to tumor antigen, alpha 2-HS glycoprotein: a novel biomarker of breast cancer screening and diagnosis. Cancer Epidemiol Biomarkers Prev. 2009. https://doi.org/10.1158/1055-9965.EPI-08-0696.CrossRefPubMed

28.

Balogh GA, Mailo DA, Corte MM, Roncoroni P, Nardi H, Vincent E, et al. Mutant p53 protein in serum could be used as a molecular marker in human breast cancer. Int J Oncol. 2006. https://doi.org/10.3892/ijo.28.4.995.CrossRefPubMed

29.

Balogh GA, Mailo D, Nardi H, Corte MM, Vincent E, Barutta E, et al. Serological levels of mutated p53 protein are highly detected at early stages in breast cancer patients. Exp Ther Med. 2010. https://doi.org/10.3892/etm_00000056.CrossRefPubMedPubMedCentral

30.

Gao RJ, Bao HZ, Yang Q, Cong Q, Song JN, Wang L. The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters. Breast Cancer Res Treat. 2005. https://doi.org/10.1007/s10549-005-4321-9.CrossRefPubMed

31.

Kulić A, Sirotković-Skerlev M, Jelisavac-Cosić S, Herceg D, Kovac Z, Vrbanec D. Anti-p53 antibodies in serum: relationship to tumor biology and prognosis of breast cancer patients. Med Oncol. 2010. https://doi.org/10.1007/s12032-009-9301-1.CrossRefPubMed

32.

Lacombe J, Mangé A, Bougnoux A-C, Prassas I, Solassol J. A multiparametric serum marker panel as a complementary test to mammography for the diagnosis of node-negative early-stage breast cancer and DCIS in young women. Cancer Epidemiol Biomarkers Prev. 2014. https://doi.org/10.1158/1055-9965.EPI-14-0267.CrossRefPubMed

33.

Lenner P, Wiklund F, Emdin SO, Arnerlöv C, Eklund C, Hallmans G, et al. Serum antibodies against p53 in relation to cancer risk and prognosis in breast cancer: a population-based epidemiological study. Br J Cancer. 1999. https://doi.org/10.1038/sj.bjc.6690148.CrossRefPubMedPubMedCentral

34.

Liu Y, Liao Y, Xiang L, Jiang K, Li S, Huangfu M, et al. A panel of autoantibodies as potential early diagnostic serum biomarkers in patients with breast cancer. Int J Clin Oncol. 2017. https://doi.org/10.1007/s10147-016-1047-0.CrossRefPubMed

35.

Lu H, Ladd J, Feng Z, Wu M, Goodell V, Pitteri SJ, et al. Evaluation of known oncoantibodies, HER2, p53, and cyclin B1, in prediagnostic breast cancer sera. Cancer Prev Res. 2012. https://doi.org/10.1158/1940-6207.CAPR-11-0558.CrossRef

36.

Pagaza-Straffon C, Marchat LA, Herrera L, Díaz-Chávez J, Avante MG, Rodríguez YP, et al. Evaluation of a panel of tumor-associated antigens in breast cancer. Cancer Biomark. 2020. https://doi.org/10.3233/CBM-190708.CrossRefPubMed

37.

Qiu C, Wang P, Wang B, Shi J, Wang X, Li T, et al. Establishment and validation of an immunodiagnostic model for prediction of breast cancer. Oncoimmunology. 2020. https://doi.org/10.1080/2162402X.2019.1682382.CrossRefPubMedPubMedCentral

38.

Ye H, Sun C, Ren P, Dai L, Peng B, Wang K, et al. Mini-array of multiple tumor-associated antigens (TAAs) in the immunodiagnosis of breast cancer. Oncol Lett. 2013. https://doi.org/10.3892/ol.2012.1062.CrossRefPubMedPubMedCentral

39.

Blixt O, Bueti D, Burford B, Allen D, Julien S, Hollingsworth M, et al. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis. Breast Cancer Res. 2011. https://doi.org/10.1186/bcr2841.CrossRefPubMedPubMedCentral

40.

Croce V, Isla-larrain MT, Demichelis SO, Gori JR, Price R, Segal-eiras A. Tissue and serum MUC1 mucin detection in breast cancer patients. Breast Cancer Res Treat. 2003. https://doi.org/10.1023/A:1026110417294.CrossRefPubMed

41.

Tang Y, Wang L, Zhang P, Wei H, Gao R, Liu X, et al. Detection of circulating anti-mucin 1 (MUC1) antibodies in breast tumor patients by indirect enzyme-linked immunosorbent assay using a recombinant MUC1 protein containing six tandem repeats and expressed in Escherichia coli. Clin Vaccine Immunol. 2010. https://doi.org/10.1128/CVI.00142-10.CrossRefPubMedPubMedCentral

42.

Zuo X, Chen L, Liu L, Zhang Z, Zhang X, Yu Q, et al. 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. Tumor Biol. 2016. https://doi.org/10.1007/s13277-015-3932-y.CrossRef

43.

Desmetz C, Bibeau F, Boissière F, Bellet V, Rouanet P, Maudelonde T, et al. Proteomics-based identification of HSP60 as a tumor-associated antigen in early stage breast cancer and ductal carcinoma in situ. J Proteome Res. 2008. https://doi.org/10.1021/pr800130d.CrossRefPubMed

44.

Hamrita B, Chahed K, Kabbage M, Guillier CL, Trimeche M, Chaïeb A, et al. Identification of tumor antigens that elicit a humoral immune response in breast cancer patients’ sera by serological proteome analysis (SERPA). Clin Chim Acta. 2008. https://doi.org/10.1016/j.cca.2008.03.017.CrossRefPubMed

45.

Huang Y, Zhang C, Chen C, Sun S, Zheng H, Wan S, et al. Investigation of circulating antibodies to ANXA1 in breast cancer. Tumor Biol. 2015. https://doi.org/10.1007/s13277-014-2751-x.CrossRef

46.

Liu W, De La Torre IG, Gutiérrez-Rivera MC, Wang B, Liu Y, Dai L, et al. Detection of autoantibodies to multiple tumor-associated antigens (TAAs) in the immunodiagnosis of breast cancer. Tumor Biol. 2015. https://doi.org/10.1007/s13277-014-2756-5.CrossRef

47.

Liu W, Li Y, Wang B, Dai L, Qian W, Zhang JY. Autoimmune Response to IGF2 mRNA-Binding Protein 2 (IMP2/p62) in Breast Cancer. Scand J Immunol. 2015. https://doi.org/10.1111/sji.12285.CrossRefPubMedPubMedCentral

48.

Oaxaca-Camacho AR, Ochoa-Mojica OR, Aguilar-Lemarroy A, Jave-Suárez LF, Muñoz-Valle JF, Padilla-Camberos E, et al. Serum analysis of women with early-stage breast cancer using a mini-array of tumor-associated antigens. Biosensors. 2020. https://doi.org/10.3390/bios10100149.CrossRefPubMedPubMedCentral

49.

Dong X, Yang M, Sun H, Lü J, Zheng Z, Li Z, et al. Combined measurement of CA 15–3 with novel autoantibodies improves diagnostic accuracy for breast cancer. Onco Targets Ther. 2013. https://doi.org/10.2147/OTT.S43122.CrossRefPubMedPubMedCentral

50.

Fernández-Grijalva AL, Aguilar-Lemarroy A, Jave-Suarez LF, Gutiérrez-Ortega A, Godinez-Melgoza PA, Herrera-Rodríguez SE, et al. Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer. J Proteomics. 2015. https://doi.org/10.1016/j.jprot.2014.07.025.CrossRefPubMed

51.

Frenkel K, Karkoszka J, Glassman T, Dubin N, Toniolo P, Taioli E, et al. Serum autoantibodies recognizing 5-hydroxymethyl-2 ’ -deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women. Cancer Epidemiol Biomarkers Prev. 1998;7(1):49–57.PubMed

52.

Le Naour F, Misek DE, Krause MC, Deneux L, Giordano TJ, Scholl S, et al. Proteomics-based identification of RS/DJ-1 as a novel circulating tumor antigen in breast cancer. Clin Cancer Res. 2001;7(11):3328–35.PubMed

53.

Kurtenkov O, Innos K, Sergejev B, Klaamas K. The thomsen-friedenreich antigen-specific antibody signatures in patients with breast cancer. Biomed Res Int. 2018. https://doi.org/10.1155/2018/9579828.CrossRefPubMedPubMedCentral

54.

Zhong L, Ge K, Zu JC, Zhao LH, Shen WK, Wang JF, et al. Autoantibodies as potential biomarkers for breast cancer. Ovid Medlin Cancer Res. 2008. https://doi.org/10.1186/bcr2091.CrossRef

55.

Piura E, Piura B. Autoantibodies to tailor-made panels of tumor-associated antigens in breast carcinoma. J Oncol. 2011. https://doi.org/10.1155/2011/982425.CrossRefPubMedPubMedCentral

56.

Dudas SP, Chatterjee M, Tainsky MA. Usage of cancer associated autoantibodies in the detection of disease. Cancer Biomark. 2010. https://doi.org/10.3233/CBM-2009-0138.CrossRefPubMedPubMedCentral

57.

Macdonald IK, Parsy-Kowalska CB, Chapman CJ. Autoantibodies: Opportunities for Early Cancer Detection. Trends in Cancer. 2017. https://doi.org/10.1016/j.trecan.2017.02.003.CrossRefPubMed

58.

Tang ZM, Ling ZG, Wang CM, Wu Y Bin, Kong JL. Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: a systematic review and meta-analysis. PLoS One. 2017. https://doi.org/10.1371/journal.pone.0182117.CrossRefPubMedPubMedCentral

59.

Xia J, Shi J, Wang P, Song C, Wang K, Zhang J, et al. Tumour-associated autoantibodies as diagnostic biomarkers for breast cancer: a systematic review and meta-analysis. Scand J Immunol. 2016. https://doi.org/10.1111/sji.12430.CrossRefPubMed

60.

Werner S, Chen H, Tao S, Brenner H. Systematic review: Serum autoantibodies in the early detection of gastric cancer. Int J Cancer. 2015. https://doi.org/10.1002/ijc.28807.CrossRefPubMedPubMedCentral

61.

Zhang H, Xia J, Wang K, Zhang J. Serum autoantibodies in the early detection of esophageal cancer: a systematic review. Tumor Biol. 2014. https://doi.org/10.1007/s13277-014-2878-9.CrossRef

Title: Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis
Authors: Thejas Kathrikolly
Sreekumaran N. Nair
Aju Mathew
Prakash P. U. Saxena
Suma Nair
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Biomarkers
Published in: Systematic Reviews / Issue 1/2022
Electronic ISSN: 2046-4053
DOI: https://doi.org/10.1186/s13643-022-02088-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2022

Determining the safety and effectiveness of Tai Chi: a critical overview of 210 systematic reviews of controlled clinical trials

The development and education of a workforce in childhood cancer services in low- and middle-income countries: a scoping review protocol

Major mistakes and errors in the use of Trial Sequential Analysis in systematic reviews or meta-analyses – protocol for a systematic review

Video-based interviewing in medicine: a scoping review

Efficacy and safety of AYUSH-64 as standalone or adjunct to standard care in COVID-19: a structured summary of protocol for a systematic review

Bone defect development in experimental canine peri-implantitis models: a systematic review