Relaxin as a potential diagnostic biomarker for ovarian cancer- A prospective study

Gkrozou, Fani; Pappa, Christina; Tsonis, Orestis; Dimitriou, Eleni; Paschopoulos, Minas

doi:10.1016/j.ejogrb.2021.03.008

Cited by 5 publications

(9 citation statements)

References 12 publications

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“…REL2 protein is predominantly expressed by the corpus luteum , and was extensively studied as a pregnancy hormone, with the levels exclusively measured by immunoassays. REL2 played a crucial role in preparing the birth canal for parturition , and was elevated in the first trimester , reaching its peak concentrations of 2.2 ng/mL. , Similar to alpha-fetoprotein, levels of REL2 in the subsequent second trimester decreased to 1–1.3 ng/mL. ,, Low levels of REL2 during pregnancy have been associated with recurrent miscarriage, toxemia of pregnancy, spontaneous abortion, ectopic pregnancy, and premature labor. − Those observations suggested that serum REL2 levels could serve as a potential marker of pregnancy complications, such as preeclampsia . In addition, REL2 has been suggested as a marker of ovarian cancer and a therapeutic target of ovarian cancer, fibrosis, and cardiovascular diseases. ,, Patients with serous adenocarcinoma had a median level of 78.1 pg/mL, a concentration well above the LOD of our IA-SRM assay (9.4 pg/mL).…”

Section: Discussionmentioning

confidence: 99%

“…18,19,27,42 REL2 protein is predominantly expressed by the corpus luteum 32,43 and was extensively studied as a pregnancy hormone, 9 with the levels exclusively measured by immunoassays. REL2 played a crucial role in preparing the birth canal for parturition 32,44 and was elevated in the first trimester 31,45 reaching its peak concentrations of 2.2 ng/mL. 31,43 Similar to alpha-fetoprotein, levels of REL2 in the subsequent second trimester decreased to 1−1.3 ng/mL.…”

Section: ■ Discussionmentioning

confidence: 99%

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Identification and Quantification of Human Relaxin Proteins by Immunoaffinity-Mass Spectrometry

Rais,

Drabovich

2024

J. Proteome Res.

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The human relaxins belong to the Insulin/IGF/Relaxin superfamily of peptide hormones, and their physiological function is primarily associated with reproduction. In this study, we focused on a prostate tissue-specific relaxin RLN1 (REL1_HUMAN protein) and a broader tissue specificity RLN2 (REL2_HUMAN protein). Due to their structural similarity, REL1 and REL2 proteins were collectively named a ‘human relaxin protein’ in previous studies and were exclusively measured by immunoassays. We hypothesized that the highly selective and sensitive immunoaffinity-selected reaction monitoring (IA-SRM) assays would reveal the identity and abundance of the endogenous REL1 and REL2 in biological samples and facilitate the evaluation of these proteins for diagnostic applications. High levels of RLN1 and RLN2 transcripts were found in prostate and breast cancer cell lines by RT-PCR. However, no endogenous prorelaxin-1 or mature REL1 were detected by IA-SRM in cell lines, seminal plasma, or blood serum. The IA-SRM assay of REL2 demonstrated its undetectable levels (<9.4 pg/mL) in healthy control female and male sera and relatively high levels of REL2 in maternal sera across different gestational weeks (median 331 pg/mL; N = 120). IA-SRM assays uncovered potential cross-reactivity and nonspecific binding for relaxin immunoassays. The developed IA-SRM assays will facilitate the investigation of the physiological and pathological roles of REL1 and REL2 proteins.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

Identification and Quantification of Human Relaxin Proteins by Immunoaffinity-Mass Spectrometry

Rais,

Drabovich

2024

J. Proteome Res.

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“…Relaxin has previously been suggested as a potential marker of ovarian cancer 43 and therapeutic target of ovarian cancer 95,96 and cardiovascular diseases 24,34,97 . Patients with serous adenocarcinoma exhibited a mean relaxin level of 78.1 pg/mL 43 , and such levels could be verified with our IA-SRM assay. Our findings may establish a baseline for future investigation of REL2 levels in disease and provide a robust assay for diagnostic applications.…”

Section: Due To Immunoassay Cross-reactivity and Uncertainty About Ex...mentioning

confidence: 99%

Identification and quantification of human relaxin proteins by immunoaffinity-mass spectrometry

Rais,

Drabovich

2024

Preprint

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The human relaxins belong to the Insulin/IGF/Relaxin superfamily of peptide hormones, and their physiological function is primarily associated with reproduction. In this study, we focused on a prostate tissue-specific relaxin RLN1 (REL1_HUMAN protein), and a broader tissue specificity RLN2 (REL2_HUMAN). Due to their structural similarity, REL1 and REL2 proteins were collectively named a "human relaxin protein" in previous studies and were exclusively measured by immunoassays. We hypothesized that the highly selective and sensitive immunoaffinity-selected reaction monitoring (IA-SRM) assays could reveal the identity and concentration of REL1 and REL2 in biological samples and facilitate the evaluation of these proteins for diagnostic applications. RT-PCR revealed the high levels of RLN1 and RLN2 transcripts in prostate and breast cancer cell lines. However, no endogenous prorelaxin-1 or mature REL1 were detected by IA-SRM in numerous biological samples. IA-SRM assay of REL2 revealed its undetectable levels (<9 pg/mL) in control female and male sera, relatively high levels of REL2 in maternal sera (median 331 pg/mL, 120 patients), and a biphasic expression of REL2 across the gestational weeks. IA-SRM assays discovered potential cross-reactivity and false-positive measurements for relaxin immunoassays. The developed IA-SRM assays will facilitate the investigation of the physiological and pathological roles of REL1 and REL2 peptide hormones.

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“…As we have mentioned above, relaxin-2 levels could be potentially employed as a circulant gynaecological and obstetrical physiopathological biomarker owing to its traditional role in reproduction [ 53 , 54 , 55 , 56 , 57 , 58 , 59 ] and also in premenstrual disorders such as premenstrual dysphoria [ 78 ]. Notwithstanding its documented role in the reproductive system, relaxin-2 is also synthesized in different organs and tissues of the human anatomy such as the brain, lungs, heart, blood vessels, liver, pancreas, small intestine, kidney, and bladder, and it is released into the circulation [ 12 , 79 ]; it is hypothesized that changes in the circulatory levels of relaxin-2 could be related to different pathological settings like diabetes [ 80 ], cancer [ 81 , 82 ], orthopaedical disarrangements [ 83 , 84 , 85 ], systemic and multiple sclerosis [ 71 , 86 ], end-stage kidney disease [ 87 ], and of course, CVDs, as we are going to explain in the following section.…”

Section: Endogenous Levels Of Relaxin-2 In Physiological Conditionsmentioning

confidence: 99%

“…Owing to its remarkable role during reproduction and pregnancy, relaxin-2 has been suggested as a biomarker in different gynaecological and obstetrical settings such as preterm delivery, preeclampsia, ectopic pregnancies, and even ovarian cancer [ 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. Apart from pregnancy, serum and plasma relaxin-2 levels could be associated with CVDs, a fact that in parallel with the role of relaxin-2 during renal and systemic haemodynamic adaptations in pregnancy, and its clear beneficial effect on cardiac function, has prompted the interest in relaxin-2 as an endogenous biomarker of several CVDs [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Relaxin-2 as a Potential Biomarker in Cardiovascular Diseases

Aragón-Herrera

Feijóo‐Bandín

Anido-Varela

et al. 2022

JPM

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The pleiotropic hormone relaxin-2 plays a pivotal role in the physiology and pathology of the cardiovascular system. Relaxin-2 exerts relevant regulatory functions in cardiovascular tissues through the specific receptor relaxin family peptide receptor 1 (RXFP1) in the regulation of cardiac metabolism; the induction of vasodilatation; the reversion of fibrosis and hypertrophy; the reduction of inflammation, oxidative stress, and apoptosis; and the stimulation of angiogenesis, with inotropic and chronotropic effects as well. Recent preclinical and clinical outcomes have encouraged the potential use of relaxin-2 (or its recombinant form, known as serelaxin) as a therapeutic strategy during cardiac injury and/or in patients suffering from different cardiovascular disarrangements, especially heart failure. Furthermore, relaxin-2 has been proposed as a promising biomarker of cardiovascular health and disease. In this review, we emphasize the relevance of the endogenous hormone relaxin-2 as a useful diagnostic biomarker in different backgrounds of cardiovascular pathology, such as heart failure, atrial fibrillation, myocardial infarction, ischemic heart disease, aortic valve disease, hypertension, and atherosclerosis, which could be relevant in daily clinical practice and could contribute to comprehending the specific role of relaxin-2 in cardiovascular diseases.

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Relaxin as a potential diagnostic biomarker for ovarian cancer- A prospective study

Cited by 5 publications

References 12 publications

Identification and Quantification of Human Relaxin Proteins by Immunoaffinity-Mass Spectrometry

Identification and Quantification of Human Relaxin Proteins by Immunoaffinity-Mass Spectrometry

Identification and quantification of human relaxin proteins by immunoaffinity-mass spectrometry

Relaxin-2 as a Potential Biomarker in Cardiovascular Diseases

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