br A Despite being the most common gynecologic malignancy th
52 A. Despite being the most common gynecologic malignancy, there are currently no early 53 detection screening tests available among asymptomatic women who are at average risk 54 for endometrial cancer. Using prediagnostic serum from both endometrial cancer cases 55 and controls, we sought to investigate for early detection serum biomarkers. 56 B. A serum biomarker panel containing six 3X FLAG Peptide (complement factor B, serotransferrin, 57 catalase, proteasome subunit beta type -6, beta-2-microglobulin, and protocadherin-18) 58 was able differentiate endometrial cancers from controls within two years of cancer 59 diagnosis using serum from patients enrolled in the Prostate, Lung, Colorectal, and 60 Ovarian Cancer Screening Trial. 61 C. The results of this study are preliminary and require further validation to determine 62 whether these biomarkers can be used clinically to predict or detect endometrial cancer 63 among postmenopausal women. 64
70 Background: Endometrial cancer is the most common gynecologic cancer in the United States.
71 However, no early detection test exists for asymptomatic women at average risk for endometrial
73 Objective: We sought to identify early detection biomarkers for endometrial cancer using
74 prediagnostic serum.
75 Study Design: We performed a nested case-control study of postmenopausal women in the
76 Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (n=78,216), including
77 112 incident endometrial cancer cases and 112 controls. Prediagnostic serum was
78 immunodepleted of high-abundance proteins and digested with sequencing grade porcine trypsin
79 via pressure cycling technology. Quantitative proteomics and phosphoproteomics was performed
80 using high-resolution liquid chromatography-tandem mass spectrometry and highly multiplexed
81 isobaric mass-tag combined with basic reversed -phase liquid chromatography. A set of proteins
82 able to predict cancer status was identified with an integrated score assessed by receiver operator
83 curve analysis.
84 Results: Mean time from blood draw to endometrial cancer diagnosis was 3.5 years (standard
85 deviation 1.9 years). There were 47 differentially abundant proteins between cases and controls
86 (P<0.05). Protein alterations with high predictive potential were selected by regression analysis
87 and compiled into an aggregate score to determine the ability to predict endometrial cancer. An
88 integrated risk score of six proteins was directly related to disease incidence in cases with blood
90 distinguished cases from controls with an area under the curve of 0.80 [95% Confidence Interval
92 Conclusions: An integrated score of six proteins using prediagnostic serum from the PLCO
93 Cancer Screening Trial distinguishes postmenopausal endometrial cancer cases from controls.
94 Validation is needed to evaluate whether this test can improve prediction or detection of
95 endometrial cancer among postmenopausal women.
97 Keywords: endometrial cancer, prediagnostic serum, early detection, biomarkers
116 The American Cancer Society estimates 63,230 new endometrial cancer cases will be
118 projected to become the third most common cancer among women in the United States by 2030
119 (2). Despite being the most common gynecologic malignancy, there are currently no early
120 detection screening tests available among asymptomatic women at average risk for endometrial
123 Although 90% of patients diagnosed with endometrial cancer report abnormal uterine
124 bleeding, only 10% of patients with postmenopausal uterine bleeding have cancer making it a
125 non-specific predictor of disease. In a report of 219 endometrial cancer patients, investigators
126 found that the interval from the onset of bleeding symptoms to diagnosis of endometrial cancer
127 was 9.7 weeks and was not associated with stage, histology or race (4). Other meta-analyses of
128 endometrial cancer patients with bleeding have not provided evidence that symptomatic patients
129 present with early stage disease earlier than those with advanced stage disease or with more
130 aggressive histologic (5). Approximately 25% of women who develop endometrial cancer are
131 diagnosed with endometrial hyperplasia, which can be present one to twenty years prior to
132 cancer diagnosis (6-8). This lengthy interval from the development of precursor lesions to the