Molecular profiling of human endometrium and endometriosis

Kaisa Huhtinen
2010 · W158456447
dissertation OA: green CC0 ⤵ 1 in-corpus citation
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This study utilized genome-wide expression analysis of endometriosis to identify subgroups, altered peritoneal tissue, a role for androgens and enzyme HSD17B6, and a new diagnostic biomarker, HE4.

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This paper aimed to identify novel diagnostic and treatment tools for endometriosis by performing genome-wide expression profiling of human endometriosis specimens and comparing them with healthy endometrium and peritoneum. Using expression-based analysis, the authors report a classification that identifies endometriosis lesion subgroups that partially align with clinical appearance but also reflect additional unknown factors, and they find altered peritoneum in women with endometriosis versus healthy controls. They also evaluate sex hormone action and metabolism and report a novel role for androgens, including high up-regulation of hydroxysteroid (17beta) dehydrogenase 6 in endometriosis tissue, which they propose could relate to pathogenesis or pain generation. Finally, they report the diagnostic biomarker HE4 as distinguishing patients with ovarian endometriotic cysts from those with malignant ovarian cancer, with the main limitation implied by the study being exploratory expression profiling rather than validated clinical performance. This paper is centrally about endometriosis — it presents molecular profiling of endometrium and endometriosis, identifies hormone- and gene-expression changes (including HSD17B6), and proposes HE4 as a diagnostic biomarker for ovarian endometriotic cysts.

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Abstract

Endometriosis is a common hormone-dependent gynecological disease leading to severe menstrual and/or chronic pelvic pain with or without subfertility. The disease is defined by the presence of endometrium-like tissue outside the uterine cavity, primarily on the pelvic peritoneum, ovaries and infiltrating organs of the peritoneal cavity. The current tools for diagnosis and treatment of endometriosis need to be improved to ensure reliable diagnosis and effective treatment. In addition, endometriosis is associated with increased risk of ovarian cancer and, therefore, the differential diagnosis between the benign and malignant ovarian cysts is of importance. \n \nThe long-term objective of the present study was to support the discovery of novel tools for diagnosis and treatment of endometriosis. This was approached by exploiting genome-wide expression analysis of endometriosis specimens. A novel expression profiling -based classification of endometriosis indicated specific subgroups of lesions partially consistent with the clinical appearance, but partially according to unknown factors. The peritoneum of women with endometriosis appeared to be altered in comparison to that of healthy control subjects, suggesting a novel aspect on the pathogenesis of the disease. The evaluation of action and metabolism of sex hormones in endometrium and endometriosis tissue indicated a novel role of androgens in regulation of the tissues. In addition, an enzyme involved in androgen and neurosteroid metabolism, hydroxysteroid (17beta) dehydrogenase 6, was found to be highly up-regulated in endometriosis tissue as compared to healthy endometrium. The enzyme may have a role in the pathogenesis of endometriosis or in the endometriosis associated pain generation. Finally, a new diagnostic biomarker, HE4, was discovered distinguishing patients with ovarian endometriotic cysts from those with malignant ovarian cancer. \n \nThe information acquired in this study enables deeper understanding of endometriosis and facilitates the development of improved diagnostic tools and more specific treatments of the disease
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Molecular profiling of human endometrium and endometriosis Pysyvä osoite Verkkojulkaisu DOI Tiivistelmä Endometriosis is a common hormone-dependent gynecological disease leading to severe menstrual and/or chronic pelvic pain with or without subfertility. The disease is defined by the presence of endometrium-like tissue outside the uterine cavity, primarily on the pelvic peritoneum, ovaries and infiltrating organs of the peritoneal cavity. The current tools for diagnosis and treatment of endometriosis need to be improved to ensure reliable diagnosis and effective treatment. In addition, endometriosis is associated with increased risk of ovarian cancer and, therefore, the differential diagnosis between the benign and malignant ovarian cysts is of importance. The long-term objective of the present study was to support the discovery of novel tools for diagnosis and treatment of endometriosis. This was approached by exploiting genome-wide expression analysis of endometriosis specimens. A novel expression profiling -based classification of endometriosis indicated specific subgroups of lesions partially consistent with the clinical appearance, but partially according to unknown factors. The peritoneum of women with endometriosis appeared to be altered in comparison to that of healthy control subjects, suggesting a novel aspect on the pathogenesis of the disease. The evaluation of action and metabolism of sex hormones in endometrium and endometriosis tissue indicated a novel role of androgens in regulation of the tissues. In addition, an enzyme involved in androgen and neurosteroid metabolism, hydroxysteroid (17beta) dehydrogenase 6, was found to be highly up-regulated in endometriosis tissue as compared to healthy endometrium. The enzyme may have a role in the pathogenesis of endometriosis or in the endometriosis associated pain generation. Finally, a new diagnostic biomarker, HE4, was discovered distinguishing patients with ovarian endometriotic cysts from those with malignant ovarian cancer. The information acquired in this study enables deeper understanding of endometriosis and facilitates the development of improved diagnostic tools and more specific treatments of the disease Kuvaus Siirretty Doriasta Sarja Turun yliopiston julkaisuja. Sarja D, Medica – Odontologica|895 Saavutettavuusominaisuudet Ei tietoa saavutettavuudesta

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endometriosischronic_pelvic_pain

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