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431 role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer
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442 reliable serum biomarker for discriminating high-risk endometrial cancer. Tumour Biol.
445 prognostic values of preoperative serum levels of YKL-40, HE-4 and DKK-3 in endometrial
448 Preoperative serum YKL-40 is a marker for detection and prognosis of endometrial cancer.
451 antigen 9 is a promising marker for early diagnosis of endometrial cancer. Asian Pac J Cancer
454 associated antigen 9 in patients with endometrial carcinoma. Int J Gynecol Cancer.
456 25.Konno R, Takano T, Sato S, Yajima A. Serum soluble fas level as a prognostic factor in
463 preoperative CA 125 level in the management of uterine cancer and prediction of clinical
467 Table 1. Demographic Characteristics of Endometrial Cancer Cases and Matched Controls
Age (at randomization)b
Body Mass Index (kg/m2)
Number of Live Births
Highest Education Level Attained
Menopausal Hormone Use
469 a P values based on c2 statistics 470 b Matching factors. Other matching factors not included in the table are study center, year of randomization, and 471 year of blood draw; there was no statistical difference in distribution between cases and controls 472 473
474 475 476 Table 2. Significantly Altered Proteins among Cases versus Controls ≤ 2 Years to Diagnosis
478 *10 proteins significantly different between cases and controls ≤ 2 years of diagnosis and also showing same rate of 479 change in concentration of protein over three time categories
480 **Paired Limma adjusted by serum albumin protein abundance
482 Figure Legends
483 484 Figure 1. Study selection process. 485 486 Figure 2. Prioritization of protein alterations with high diagnostic potential. Among cases where
487 blood draw occurred ≤ 2 years of endometrial cancer diagnosis, there are 47 proteins
488 significantly altered between cases and controls (P<0.05). Comparative analyses of these
489 abundance trends for cases diagnosed > 2 years to ≤ 5 years with matched controls and > 5 years
490 with matched controls resulted in the prioritization of ten protein candidates reflecting identical
491 abundance trends as observed in cases diagnosed within 2 years from blood draw. Six high-
492 confidence candidates were selected from the ten by LASSO regression analysis; figure depicts
493 case versus control abundance trends for these six candidates in patients diagnosed with
495 496 Figure 3. A serum-based, integrated risk score to predict endometrial cancer. Protein alterations
497 with high diagnostic potential were selected by LASSO regression analysis and assembled into
498 an aggregate score calculated for each case to predict the relative risk of having endometrial
499 cancer. A: Integrated risk scores are directly related to disease incidence in patients with blood
501 Integrated risk scores exhibit a linear relationship from time of blood draw to receiving a
502 diagnosis of endometrial cancer.
504 Figure 4. Evaluation of a serum-based, integrated risk score to predict endometrial cancer.
505 Receiver operator curve evaluating integrated score for 6 high-confidence proteins (complement
506 factor B, serotransferrin, catalase, proteasome subunit beta type-6, beta-2-microglobulin, and