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Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients

Year 2024, Volume: 14 Issue: 2, 888 - 893, 01.06.2024
https://doi.org/10.21597/jist.1447517

Abstract

Anti-nuclear antibodies (ANAs) are autoantibodies synthesized in response to the cell nucleus contents and use as biomarkers of systemic autoimmune diseases. Inflammation, apoptosis and necrosis of the cells are consequences that accompany breast cancer against which autoantibodies will be produced. In this study, we aimed to evaluate the presence of ANAs and anti-extractable nuclear antigens (anti-ENAs) in breast cancer. A total of 33 luminal A and luminal B breast cancer patients were assessed for presence of ANAs and anti-ENAs. All the patients had received hormone therapy at least for 6 months before the tests. Patients were screened to ANAs by indirect immunofluorescence on human epithelial type 2 (HEp-2) cells. AESKUBLOTS® ANA-17 comp kit was used to identify the concentrations of U1-snRNP, snRNP/Sm, SmD1, dsDNA, SS-A/Ro 60, SS-A/Ro 52, SS-B/La antibodies. Fifteen (45.5%) patients were luminal A and 18 (54.5%) patients were luminal B. The median of age was 57 and the median of tumor size was 25. 19 (57.6%) patients had grade I or II and 14 (42.4%) had grade III. 3 patients had ANAs test positive. All the patients who had positive ANA test were luminal A breast cancer and had grade I or II tumors and positive lymph node, whereas, pathological tumor stage were varied. No statistically significant association was found between ANAs positivity and molecular subtype, age, body mass index (BMI), grade, tumor stage or lymph node involvement. Moreover, there were negative correlations between the anti-U1-snRNP and anti-dsDNA with Ki-67 and a correlation between anti-snRNP/Sm and anti-SS-A/Ro 52 was found. Comparing with luminal A, anti-U1-snRNP and anti-snRNP/Sm concentrations were statistically significantly lower in luminal B tumors (p= 0.015 and 0.016 respectively). Patients who had high grade tumors showed low concentrations of anti-snRNP/Sm (p=0.027), whereas patients who had lymph node metastasis showed high concentrations of anti-U1-snRNP (p=0.031). ANAs positivity was more common in luminal A breast cancer patients compared with luminal B. Anti-U1-snRNP and anti-snRNP/Sm concentrations were lower in luminal B. Moreover, patients who had high grade tumors showed low concentrations of anti-snRNP/Sm, whereas those who had lymph node metastasis showed high concentrations of anti-U1-snRNP.

Ethical Statement

I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed.

Supporting Institution

İstanbul University and Biruni University. I appreciate your timely review and decision on this manuscript. Yours sincerely,

Thanks

Thank you and best regards.

References

  • Admou, B., Eddehbi, F. E., Elmoumou, L., Elmojadili, S., Salami, A., Oujidi, M., ... & Hazime, R. (2022). Anti-double stranded DNA antibodies: A rational diagnostic approach in limited-resource settings. Practical Laboratory Medicine, 31, e00285.
  • Chapman, C., Murray, A., Chakrabarti, J., Thorpe, A., Woolston, C., Sahin, U., ... & Robertson, J. (2007). Autoantibodies in breast cancer: their use as an aid to early diagnosis. Annals of oncology, 18(5), 868-873.
  • Choi, M.Y., Costenbader, K.H. Understanding the concept of pre-clinical autoimmunity: prediction and prevention of systemic lupus erythematosus: identifying risk factors and developing strategies against disease development. Frontiers in Immunology, 2022, 13: 890522.
  • Cleaton, N., & Bateman, J. (2020). P92 Referral with a positive antinuclear antibody? Lessons from prospective triage and diagnosis in a single-centre service evaluation of 1,547 new rheumatology referrals. Rheumatology, 59(Supplement_2), keaa111-090.
  • Erkanli, A., Taylor, D. D., Dean, D., Eksir, F., Egger, D., Geyer, J., ... & Roden, R. B. (2006). Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection. Cancer research, 66(3), 1792-1798.
  • Fernández Madrid, F., Maroun, M. C., Olivero, O. A., Long, M., Stark, A., Grossman, L. I., ... & Peebles, C. (2015). Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis. BMC cancer, 15(1), 1-15.
  • Hong, C. Q., Weng, X. F., Huang, X. C., Chu, L. Y., Wei, L. F., Lin, Y. W., ... & Peng, Y. H. (2021). A panel of tumor-associated autoantibodies for the detection of early-stage breast cancer. Journal of Cancer, 12(9), 2747.
  • Lacombe, J., Mangé, A., & Solassol, J. (2014). Use of autoantibodies to detect the onset of breast cancer. Journal of immunology research, 2014.
  • Ling, M.; Murali, M. Antinuclear antibody tests. Clinics in Laboratory Medicine, 2019, 39.4: 513-524.
  • Liu, B. C., DiJohnson, D. A., & O'Rourke, D. J. (2012). Antibody profiling with protein antigen microarrays in early stage cancer. Expert opinion on medical diagnostics, 6(3), 187-196.
  • Mohammed, M. E. A., & Abdelhafiz, K. (2015). Autoantibodies in the sera of breast cancer patients: antinuclear and anti-double stranded DNA antibodies as example. Journal of Cancer Research and Therapeutics, 11(2), 341-344.
  • Morimoto, K., Yamada, T., Nakamura, R., Katayama, Y., Tanaka, S., Takumi, C., ... & Takayama, K. (2020). Impact of preexisting antinuclear antibodies on combined immunotherapy and chemotherapy in advanced non-small cell lung cancer patients. Medical Oncology, 37, 1-7.
  • Nisihara, R., Machoski, M. C. C., Neppel, A., Maestri, C. A., Messias-Reason, I., & Skare, T. L. (2018). Anti-nuclear antibodies in patients with breast cancer. Clinical & Experimental Immunology, 193(2), 178-182.
  • Otsuka, T., Hashii, Y., Murayama, S., Ishizuka, Y., Kojitani, Y., Nishio, M., & Kudo, T. (2023). Checkpoint inhibitor-induced gastritis followed by delayed severe hepatitis in a patient with lung metastases of head and neck squamous cell carcinoma: a case report. Frontiers in Oncology, 13, 1164236
  • Sexauer, D., Gray, E., & Zaenker, P. (2022). Tumour-associated autoantibodies as prognostic cancer biomarkers-a review. Autoimmunity reviews, 21(4), 103041.
  • Shiel Jr, W. C., & Jason, M. (1989). The diagnostic associations of patients with antinuclear antibodies referred to a community rheumatologist. The Journal of Rheumatology, 16(6), 782-785.
  • Tan, H. T., Low, J., Lim, S. G., & Chung, M. C. (2009). Serum autoantibodies as biomarkers for early cancer detection. The FEBS journal, 276(23), 6880-6904.
  • Turgutalp, K., Oğuz Gök, E., Akça, M., & Kıyım, A. A. (2013). Anti-dsDNA positivity in a patient with prostate cancer and acute kidney ınjury: a case report. Türk Nefroloji Diyaliz ve Transplantasyon Dergisi, 22(2), 221-223.

Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients

Year 2024, Volume: 14 Issue: 2, 888 - 893, 01.06.2024
https://doi.org/10.21597/jist.1447517

Abstract

Anti-nükleer antikorlar (ANAs), hücre çekirdek içeriğine karşı üretilen otoantikorlardır ve sistemik otoimmün hastalıkların biyobelirteçleri olarak kullanılırlar. İnflamasyon, apoptoz ve hücre nekrozu, meme kanseri ile ilişkili olarak ortaya çıkan hücresel sonuçlardır ve bu duruma karşı otoantikorlar üretilebilir. Bu çalışmada, meme kanserinde ANA'ların ve anti-ekstrakte edilebilir nükleer antijenlerin (anti-ENAs) varlığını değerlendirmeyi amaçladık. Toplam 33 lümenal A ve lümenal B meme kanseri hastası, ANA'ların ve anti-ENAs'ın varlığı açısından değerlendirildi. Tüm hastalar, testlerden en az 6 ay önce hormon terapisi almışlardır. Hastalar, insan epitel tip 2 (HEp-2) hücrelerinde endirekt immünoflorasansta ANA'lar için taranmıştır. U1-snRNP, snRNP/Sm, SmD1, dsDNA, SS-A/Ro 60, SS-A/Ro 52, SS-B/La antikor konsantrasyonlarını belirlemek için AESKUBLOTS® ANA-17 comp kiti kullanıldı. Onbeş hastanın (%45.5) lümenal A ve 18 hastanın (%54.5) lümenal B olduğu belirlendi. Ortalama yaş 57, tümör boyutu ise 25 tir. Hastaların %57.6'sında I veya II derece, %42.4'ünde III derece tümör vardı ve üç hasta ANA testi pozitifti. Pozitif ANA testi olan tüm hastalar lümenal A meme kanserliydi ve I veya II derece tümöre sahip olup pozitif lenf noduna sahipti; ancak patolojik tümör evresi değişkenlik gösteriyordu. ANA pozitifliği ile moleküler alt tip, yaş, vücut kitle indeksi (VKİ), derece, tümör evresi veya lenf nodu tutulumu arasında istatistiksel olarak anlamlı bir ilişki bulunamamıştır. Ayrıca, anti-U1-snRNP ve anti-dsDNA'nın Ki-67 ile negatif, anti-snRNP/Sm ve anti-SS-A/Ro 52'nin ise pozitif bir korelasyonu bulunmuştur. Lümenal A ile karşılaştırıldığında, anti-U1-snRNP ve anti-snRNP/Sm konsantrasyonları lümenal B tümörlerinde istatistiksel olarak önemli ölçüde düşük bulunmuştur (sırasıyla p= 0.015 ve 0.016). Yüksek dereceli tümöre sahip hastalar, düşük anti-snRNP/Sm konsantrasyonları gösterirken, lenf nodu metastazına sahip olanlar yüksek anti-U1-snRNP konsantrasyonları sergilemiştir (sırasıyla p=0.027 ve 0.031). ANA pozitifliği, lümenal A meme kanseri hastalarında lümenal B'ye kıyasla daha yaygın bulunmuştur. Anti-U1-snRNP ve anti-snRNP/Sm konsantrasyonları lümenal B'de daha düşüktür. Ayrıca, yüksek dereceli tümöre sahip hastalar düşük anti-snRNP/Sm konsantrasyonları gösterirken, lenf nodu metastazı olanlar yüksek anti-U1-snRNP konsantrasyonları sergilemiştir.

References

  • Admou, B., Eddehbi, F. E., Elmoumou, L., Elmojadili, S., Salami, A., Oujidi, M., ... & Hazime, R. (2022). Anti-double stranded DNA antibodies: A rational diagnostic approach in limited-resource settings. Practical Laboratory Medicine, 31, e00285.
  • Chapman, C., Murray, A., Chakrabarti, J., Thorpe, A., Woolston, C., Sahin, U., ... & Robertson, J. (2007). Autoantibodies in breast cancer: their use as an aid to early diagnosis. Annals of oncology, 18(5), 868-873.
  • Choi, M.Y., Costenbader, K.H. Understanding the concept of pre-clinical autoimmunity: prediction and prevention of systemic lupus erythematosus: identifying risk factors and developing strategies against disease development. Frontiers in Immunology, 2022, 13: 890522.
  • Cleaton, N., & Bateman, J. (2020). P92 Referral with a positive antinuclear antibody? Lessons from prospective triage and diagnosis in a single-centre service evaluation of 1,547 new rheumatology referrals. Rheumatology, 59(Supplement_2), keaa111-090.
  • Erkanli, A., Taylor, D. D., Dean, D., Eksir, F., Egger, D., Geyer, J., ... & Roden, R. B. (2006). Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection. Cancer research, 66(3), 1792-1798.
  • Fernández Madrid, F., Maroun, M. C., Olivero, O. A., Long, M., Stark, A., Grossman, L. I., ... & Peebles, C. (2015). Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis. BMC cancer, 15(1), 1-15.
  • Hong, C. Q., Weng, X. F., Huang, X. C., Chu, L. Y., Wei, L. F., Lin, Y. W., ... & Peng, Y. H. (2021). A panel of tumor-associated autoantibodies for the detection of early-stage breast cancer. Journal of Cancer, 12(9), 2747.
  • Lacombe, J., Mangé, A., & Solassol, J. (2014). Use of autoantibodies to detect the onset of breast cancer. Journal of immunology research, 2014.
  • Ling, M.; Murali, M. Antinuclear antibody tests. Clinics in Laboratory Medicine, 2019, 39.4: 513-524.
  • Liu, B. C., DiJohnson, D. A., & O'Rourke, D. J. (2012). Antibody profiling with protein antigen microarrays in early stage cancer. Expert opinion on medical diagnostics, 6(3), 187-196.
  • Mohammed, M. E. A., & Abdelhafiz, K. (2015). Autoantibodies in the sera of breast cancer patients: antinuclear and anti-double stranded DNA antibodies as example. Journal of Cancer Research and Therapeutics, 11(2), 341-344.
  • Morimoto, K., Yamada, T., Nakamura, R., Katayama, Y., Tanaka, S., Takumi, C., ... & Takayama, K. (2020). Impact of preexisting antinuclear antibodies on combined immunotherapy and chemotherapy in advanced non-small cell lung cancer patients. Medical Oncology, 37, 1-7.
  • Nisihara, R., Machoski, M. C. C., Neppel, A., Maestri, C. A., Messias-Reason, I., & Skare, T. L. (2018). Anti-nuclear antibodies in patients with breast cancer. Clinical & Experimental Immunology, 193(2), 178-182.
  • Otsuka, T., Hashii, Y., Murayama, S., Ishizuka, Y., Kojitani, Y., Nishio, M., & Kudo, T. (2023). Checkpoint inhibitor-induced gastritis followed by delayed severe hepatitis in a patient with lung metastases of head and neck squamous cell carcinoma: a case report. Frontiers in Oncology, 13, 1164236
  • Sexauer, D., Gray, E., & Zaenker, P. (2022). Tumour-associated autoantibodies as prognostic cancer biomarkers-a review. Autoimmunity reviews, 21(4), 103041.
  • Shiel Jr, W. C., & Jason, M. (1989). The diagnostic associations of patients with antinuclear antibodies referred to a community rheumatologist. The Journal of Rheumatology, 16(6), 782-785.
  • Tan, H. T., Low, J., Lim, S. G., & Chung, M. C. (2009). Serum autoantibodies as biomarkers for early cancer detection. The FEBS journal, 276(23), 6880-6904.
  • Turgutalp, K., Oğuz Gök, E., Akça, M., & Kıyım, A. A. (2013). Anti-dsDNA positivity in a patient with prostate cancer and acute kidney ınjury: a case report. Türk Nefroloji Diyaliz ve Transplantasyon Dergisi, 22(2), 221-223.
There are 18 citations in total.

Details

Primary Language English
Subjects Genetic Immunology, Genetics (Other)
Journal Section Moleküler Biyoloji ve Genetik / Moleculer Biology and Genetic
Authors

Elif Aslan 0000-0002-3081-9004

Asmaa Abuaisha 0000-0003-2869-6620

Selman Emiroğlu 0000-0001-9333-6926

Mehmet Ali Dogan 0000-0003-3324-3028

Early Pub Date May 28, 2024
Publication Date June 1, 2024
Submission Date March 7, 2024
Acceptance Date April 17, 2024
Published in Issue Year 2024 Volume: 14 Issue: 2

Cite

APA Aslan, E., Abuaisha, A., Emiroğlu, S., Dogan, M. A. (2024). Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients. Journal of the Institute of Science and Technology, 14(2), 888-893. https://doi.org/10.21597/jist.1447517
AMA Aslan E, Abuaisha A, Emiroğlu S, Dogan MA. Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients. J. Inst. Sci. and Tech. June 2024;14(2):888-893. doi:10.21597/jist.1447517
Chicago Aslan, Elif, Asmaa Abuaisha, Selman Emiroğlu, and Mehmet Ali Dogan. “Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients”. Journal of the Institute of Science and Technology 14, no. 2 (June 2024): 888-93. https://doi.org/10.21597/jist.1447517.
EndNote Aslan E, Abuaisha A, Emiroğlu S, Dogan MA (June 1, 2024) Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients. Journal of the Institute of Science and Technology 14 2 888–893.
IEEE E. Aslan, A. Abuaisha, S. Emiroğlu, and M. A. Dogan, “Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients”, J. Inst. Sci. and Tech., vol. 14, no. 2, pp. 888–893, 2024, doi: 10.21597/jist.1447517.
ISNAD Aslan, Elif et al. “Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients”. Journal of the Institute of Science and Technology 14/2 (June 2024), 888-893. https://doi.org/10.21597/jist.1447517.
JAMA Aslan E, Abuaisha A, Emiroğlu S, Dogan MA. Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients. J. Inst. Sci. and Tech. 2024;14:888–893.
MLA Aslan, Elif et al. “Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients”. Journal of the Institute of Science and Technology, vol. 14, no. 2, 2024, pp. 888-93, doi:10.21597/jist.1447517.
Vancouver Aslan E, Abuaisha A, Emiroğlu S, Dogan MA. Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients. J. Inst. Sci. and Tech. 2024;14(2):888-93.