Dataset Information

Development and validation of circulating CA125 prediction models in postmenopausal women.

ABSTRACT:

Background

Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker.

Methods

We developed and validated linear and dichotomous (?35?U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n?=?26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n?=?861), the Nurses' Health Studies (NHS/NHSII, n?=?81), and the New England Case Control Study (NEC, n?=?923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC.

Result

The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r?=?0.18) and external validation datasets (r?=?0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset.

Conclusions

The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.

SUBMITTER: Sasamoto N

PROVIDER: S-EPMC6878636 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Development and validation of circulating CA125 prediction models in postmenopausal women.

Sasamoto Naoko N Babic Ana A Rosner Bernard A BA Fortner Renée T RT Vitonis Allison F AF Yamamoto Hidemi H Fichorova Raina N RN Titus Linda J LJ Tjønneland Anne A Hansen Louise L Kvaskoff Marina M Fournier Agnès A Mancini Francesca Romana FR Boeing Heiner H Trichopoulou Antonia A Peppa Eleni E Karakatsani Anna A Palli Domenico D Grioni Sara S Mattiello Amalia A Tumino Rosario R Fiano Valentina V Onland-Moret N Charlotte NC Weiderpass Elisabete E Gram Inger T IT Quirós J Ramón JR Lujan-Barroso Leila L Sánchez Maria-Jose MJ Colorado-Yohar Sandra S Barricarte Aurelio A Amiano Pilar P Idahl Annika A Lundin Eva E Sartor Hanna H Khaw Kay-Tee KT Key Timothy J TJ Muller David D Riboli Elio E Gunter Marc M Dossus Laure L Trabert Britton B Wentzensen Nicolas N Kaaks Rudolf R Cramer Daniel W DW Tworoger Shelley S SS Terry Kathryn L KL

Journal of ovarian research 20191126 1

<h4>Background</h4>Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker.<h4>Methods</h4>We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian can ...[more]

PMID: 31771659

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Project description:Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA. In an observational, open, non-randomized, controlled study uterine tissues were collected in order to generate endometrial gene expression profiles. healthy postmenopausal women were enrolled into the following treatment groups: Control-group; Tibolone-group, 2,5 mg of tibolone (administered orally) every day, starting 21 days prior to surgery; Estradiol-group, 2 mg of estradiol (administered orally) every day, starting 21 days prior to surgery; Estradiol+progestagen-group, 2 mg of estradiol (administered orally) and 5 mg of MPA (Medroxy Progesteroneacetate, administered orally) every day, starting 21 days prior to surgery. Pure (100%) endometrium was isolated from the snap-frozen uterine tissues and used for RNA isolation. RNA was labeled and hybridized to whole genome Affymetrix U133plus2 GeneChips containing 54,614 probe sets, representing approximately 47,000 transcripts. Relative to the control group, 940 genes are regulated in the endometrium of E2 treated patients, whereas only 198 genes are significantly regulated in endometria from tibolone or E2+MPA treated patients. Furthermore, only 9% of E2 regulated genes are also regulated by tibolone (85 out of 940), only 5% are also regulated by E2+MPA treatment and the overlap between tibolone and E2+MPA treatment is about 10%. This indicated that tibolone-treatment results in a weak endometrial profile similarity to E2 treatment and no profile similarity to E2+MPA treatment. A more detailed analysis showed that down stream processes, such as regulation of the cell cycle, angiogenesis and cell proliferation are almost not affected by tibolone treatment but, in contrast, are significantly affected by E2. For example, upon staining with Ki67, a marker for mitotic activity, significantly increased stromal as well as glandular cell proliferation was observed in the endometria from the E2-only treated group, while tibolone treatment resulted only in a slight increase in stromal cell proliferation (and no increase in glandular cell proliferation). These results indicate that in contrast to long-term tibolone use, short-term (21-days) use results in some estrogenic stimulation of the endometrium, which is clearly far less and rather different from what is observed during E2 treatment. References: Klaassens et al., 2006 Hanifi-Moghaddam et al., 2007 Verheul et al., 2007

Dataset Information

Development and validation of circulating CA125 prediction models in postmenopausal women.

Background

Methods

Result

Conclusions

Publications

Development and validation of circulating CA125 prediction models in postmenopausal women.

Similar Datasets

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