16α-hydroxyestrone and its receptor complex: high affinity antigen for antibodies from prostate cancer patients

Wahid Ali Khan; Mohd. Wajid Ali Khan

doi:10.31083/jomh.2021.103

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IMR Press / JOMH / Volume 17 / Issue 4 / DOI: 10.31083/jomh.2021.103

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-hydroxyestrone and its receptor complex: high affinity antigen for antibodies from prostate cancer patients

Wahid Ali Khan^1,*, Mohd. Wajid Ali Khan^2,3

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¹ Department of Clinical Biochemistry, College of Medicine, King Khalid University, 960 Abha, Kingdom of Saudi Arabia

² Department of Chemistry, College of Science, University of Hail, 2440 Hail, Kingdom of Saudi Arabia

³ Molecular Diagnostic and Personalised Therapeutics Unit, University of Hail, 2440 Hail, Kingdom of Saudi Arabia

^*Correspondence: wahidalikhan@rediffmail.com (Wahid Ali Khan)

J. Mens. Health 2021, 17(4), 117–127; https://doi.org/10.31083/jomh.2021.103

Submitted: 12 April 2021 | Accepted: 7 June 2021 | Published: 30 September 2021

(This article belongs to the Special Issue Biomarkers for Prostate Cancer)

This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Abstract

Background and objectives: Elevated levels of 16 $\alpha$ -hydroxyestrone (16 $\alpha$ -OHE ${}_{1}$ ) have been linked to increased risk of prostate cancer (PC) and estrogen receptor (ER) had been expressed in prostate tissue but the combined effect of 16 $\alpha$ -OHE ${}_{1}$ and ER ( $\alpha$ ) is lacking. We investigated the binding specificity of antibodies from PC with 16 $\alpha$ -OHE ${}_{1}$ -ER complex in the sera from PC patients.

Materials and methods: The antibodies in the serum from 60 PC patients and 40 control subjects were evaluated from ELISA (direct binding and competition) and quantitative precipitin titration. Competition ELISA was also used to estimates 16 $\alpha$ -OHE ${}_{1}$ concentration and 2-hydroxyestrone (2-OHE ${}_{1}$ )/16 $\alpha$ -OHE ${}_{1}$ ratio in PC patients.

Results: Antibodies from PC patients demonstrate high binding to 16 $\alpha$ -OHE ${}_{1}$ -ER in comparison to ER (p $<$ 0.05) or 16 $\alpha$ -OHE ${}_{1}$ (p $<$ 0.001). The relative affinity of PC IgG was found to be high for 16 $\alpha$ -OHE ${}_{1}$ -ER (1.19 $\times$ 10 ${}^{-7}$ M) as compared to ER (1.45 $\times$ 10 ${}^{-6}$ M) or 16 $\alpha$ -OHE ${}_{1}$ (1.13 $\times$ 10 ${}^{-6}$ M).

Conclusion: High affinity of PC IgG with 16 $\alpha$ -OHE ${}_{1}$ -ER might explain the possible antigenic role and 16 $\alpha$ -OHE ${}_{1}$ -ER acted as high affinity antigen for antibodies from PC. The interaction between 16 $\alpha$ -OHE ${}_{1}$ and ER makes a complex in the prostate tissues and this may generate antibodies against this complex in the cancer patients.

Keywords

Prostate cancer

16α-hydroxyestrone

Estrogen receptor

ELISA

Antibodies

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Fig. 1.

Direct binding ELISA of controls and prostate cancer (PC) patients. Direct binding enzyme-linked immunosorbent assay of control (n = 40) and PC antibodies (n = 60) to 16 $\alpha$ -OHE ${}_{1}$ -ER ( $\blacksquare$ ), ER (░) and 16 $\alpha$ -OHE ${}_{1}$ ( $\square$ ). Microtitre plates were coated with 100 $\mu{}$ L of respective antigen (2.5 $\mu{}$ g/mL). The reaction was developed with p-nitrophenyl phosphate as the substrate and the absorbance was recorded at 410 nmas described in “Materials and Methods”. Each histogram represents the mean $\pm{}$ SD. ${}^{\#}$ p $<$ 0.001, p $<$ 0.001, significantly higher binding than normal sera and 16 $\alpha$ -OHE ${}_{1}$ in PC; p $<$ 0.05 significantly higher binding than ER in PC.

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J. Mens. Health Print ISSN 1875-6867 Electronic ISSN 1875-6859