scholarly journals Integrating Circulating Tumor DNA Features and Plasma Protein Markers to Detected Early Lymphoid Neoplasm

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4489-4489
Author(s):  
Xinhua Wang ◽  
Yu Chang ◽  
Dandan Zhu ◽  
Shiyong Li ◽  
Shuaipeng Geng ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Risk Score ◽  
Peripheral Blood ◽  
Fragment Size ◽  
Stage I ◽  
Protein Markers ◽  
Lymphoid Neoplasm ◽  
Clinical Laboratories ◽  
Crs Model ◽  
Privately Held

Abstract Introduction The disease burden of lymphoid neoplasm has been rising in China over the last decade. But most patients manifest with advanced stage disease at initial diagnosis, and the prognosis is poor with a 5-year survival rate of 38.3%. Here we reported a novel multivariate cancer risk score (CRS) model which is used to detect early lymphoid neoplasm from the peripheral blood. It incorporates three cancer hallmarks, copy number aberrations (CNA) and fragment size (FS) via shallow whole genome sequencing (sWGS) from cell-free DNA (cfDNA), and a panel of seven tumor protein markers in a single blood draw (10ml). Methods 44 newly diagnosed and untreated stage I-IV lymphoid neoplasm patients and 247 healthy individuals with no cancer diagnosis were enrolled in this study. 10ml peripheral blood was collected from each participant after enrollment. cfDNA was extracted and subjected to sWGS whereas plasma was subjected to measure the levels of 7 PTMs. The cancer risk score (CRS) of a subject was calculated via an established CRS model [1]. Results Firstly, genomic and epigenetic features were explored from cfDNA sWGS results. CNA is a ubiquitous genomic hallmark in a wide spectrum of cancers. In this study, 26 of the 44 (59.1%) lymphoid neoplasm patients had CNA in at least one genomic segment (>5Mb). FS feature of cfDNA bears the correspondence of the epigenetic landscapes of cells that give rise to those cfDNA fragments. When CNA was combined with FS, 29 (65.9%) patients were able to be detected by the CNA+FS classifier. On the other hand, 13 (29.5%) patients were tested positive by PTMs alone, indicating non-DNA molecular surrogates can also serve as cancer biomarkers with acceptable performance. When CNA, FS and PTM were incorporated into a multidimensional and multivariate CRS model, it achieved the best performance allowing 31 (70.0%) lymphoid neoplasm cases to be identified with a positive predictive value (PPV) of 86.1% at 98.0% specificity. The sensitivity of CRS model increases with the advances of disease with a sensitivity of 50.0% in early stage (stage I -Ⅱ) and 90.0% in late stage (stage Ⅲ-Ⅳ). Conclusion In summary, this study provides an efficient and non-invasive method to detect lymphoid neoplasm. Instead of relying only on one dimension of cancer markers, the multidimensional approach which incorporating CNA, fragment size and protein markers is plausible in early detection of lymphoid neoplasm with sufficient accuracy and robustness. Disclosures Zhu: Clinical Laboratories, Shenyou Bio: Current Employment. Li: SeekIn Inc.: Current Employment, Current holder of individual stocks in a privately-held company. Geng: Clinical Laboratories, Shenyou Bio: Current Employment. Chang: Clinical Laboratories, Shenyou Bio: Current Employment. Chen: SeekIn Inc: Current Employment, Current holder of individual stocks in a privately-held company. Mao: SeekIn Inc: Current Employment, Current holder of individual stocks in a privately-held company.

scholarly journals Development of a blood-based cancer screening assay with a novel multivariate cancer risk score (MCRS) model by integrating shallow WGS data and plasma protein markers.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 45-45 ◽  
Author(s):  
Mao Mao ◽  
Shiyong Li ◽  
Qingqi Ren ◽  
Guolin Zhong ◽  
Ruizhen Li ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Pregnant Women ◽  
Cancer Patients ◽  
Risk Score ◽  
Cancer Mortality ◽  
Wide Spectrum ◽  
Prospective Clinical Study ◽  
Protein Markers ◽  
Blood Draw ◽  
Risk Of Cancer

45 Background: Despite the increase of our knowledge about carcinogenesis and recent successful development of innovative cancer drugs, cancer mortality has only slightly decreased in the past decades. Cancer early detection is probably the most cost-effective means to reduce cancer mortality as prognosis is much better when cancer is detected and treated at the early stage. Recently studies have demonstrated that blood-based mutation detection approaches may be effective to identify asymptomatic cancer patients from general population. Methods: Here we reported a novel multivariate cancer risk score (MCRS) model that interrogates shallow whole genome sequencing (WGS) data from cell-free DNA (cfDNA) and protein markers results in a single blood draw. Results: In a prospective clinical study consisting of 76 stage I-IV cancer patients and 152 normal individuals, the MCRS model demonstrated 60% sensitivity at 98.5% specificity. In order to validate clinical utility of the MCRS model in detection of cancer patients, we collated the data from a previous study of occult maternal malignancies from 1.93 million pregnant women undergoing NIPT test between 2016 and 2017. 466 out of the 639 pregnant women who tested positive for multiple chromosomal aneuploidies (MCAs) in the initial NIPTs (i.e. 0.06 - 0.1x WGS), have also underwent the protein markers test. Out of the 466 subjects, 39 maternal malignant cancer cases were diagnosed with a median follow-up of 399 days (IR, 303 - 487 days) by imaging and histology. The cancer patients presented a wide spectrum of cancer types, the most frequent being breast cancer (10 cases), liver cancer (8) and lymphoma (8), at stage II to IV. This subgroup of 466 subjects was selected as an independent validation cohort for our study. Through our new method, we analyzed shallow WGS and proteins data. The MCRS model allowed 28 of the 39 (71.8%) cancer cases to be identified with a positive predictive value of 73.7% and specificity of 97.7%. Conclusions: Taken together, these data demonstrate the MCRS model holds promise for detecting cancer in asymptomatic individuals, particularly in the populations at high risk of cancer.

Abstract 881: Benchmarking genome-wide polygenic risk score development techniques in colorectal cancer risk prediction

2021 ◽  
Author(s):  
Minta Thomas ◽  
Lori C Sakoda ◽  
Jeffrey K Lee ◽  
Mark A Jenkins ◽  
Andrea Burnett-Hartman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Risk Score ◽  
Colorectal Cancer Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide

scholarly journals A streamlined model for use in clinical breast cancer risk assessment maintains predictive power and is further improved with inclusion of a polygenic risk score

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245375
Author(s):  
Richard Allman ◽  
Erika Spaeth ◽  
John Lai ◽  
Susan J. Gross ◽  
John L. Hopper
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
African American ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Risk Score ◽  
Clinical Risk Factors ◽  
Polygenic Risk Score ◽  
Gail Model ◽  
Clinical Risk

Five-year absolute breast cancer risk prediction models are required to comply with national guidelines regarding risk reduction regimens. Models including the Gail model are under-utilized in the general population for various reasons, including difficulty in accurately completing some clinical fields. The purpose of this study was to determine if a streamlined risk model could be designed without substantial loss in performance. Only the clinical risk factors that were easily answered by women will be retained and combined with an objective validated polygenic risk score (PRS) to ultimately improve overall compliance with professional recommendations. We first undertook a review of a series of 2,339 Caucasian, African American and Hispanic women from the USA who underwent clinical testing. We first used deidentified test request forms to identify the clinical risk factors that were best answered by women in a clinical setting and then compared the 5-year risks for the full model and the streamlined model in this clinical series. We used OPERA analysis on previously published case-control data from 11,924 Gail model samples to determine clinical risk factors to include in a streamlined model: first degree family history and age that could then be combined with the PRS. Next, to ensure that the addition of PRS to the streamlined model was indeed beneficial, we compared risk stratification using the Streamlined model with and without PRS for the existing case-control datasets comprising 1,313 cases and 10,611 controls of African-American (n = 7421), Caucasian (n = 1155) and Hispanic (n = 3348) women, using the area under the curve to determine model performance. The improvement in risk discrimination from adding the PRS risk score to the Streamlined model was 52%, 46% and 62% for African-American, Caucasian and Hispanic women, respectively, based on changes in log OPERA. There was no statistically significant difference in mean risk scores between the Gail model plus risk PRS compared to the Streamlined model plus PRS. This study demonstrates that validated PRS can be used to streamline a clinical test for primary care practice without diminishing test performance. Importantly, by eliminating risk factors that women find hard to recall or that require obtaining medical records, this model may facilitate increased clinical adoption of 5-year risk breast cancer risk prediction test in keeping with national standards and guidelines for breast cancer risk reduction.

scholarly journals Ovarian cancer risk score predicts chemo-response and outcome in epithelial ovarian carcinoma patients

2021 ◽  
Vol 32 ◽  
Author(s):  
Hsiao-Yun Lu ◽  
Yi-Jou Tai ◽  
Yu-Li Chen ◽  
Ying-Cheng Chiang ◽  
Heng-Cheng Hsu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Ovarian Carcinoma ◽  
Risk Score ◽  
Epithelial Ovarian Carcinoma ◽  
Ovarian Cancer Risk

scholarly journals Translocation (14;18)-positive cells are present in the circulation of the majority of patients with localized (stage I and II) follicular non- Hodgkin's lymphoma

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2510-2516 ◽  
Author(s):  
AC Lambrechts ◽  
PE Hupkes ◽  
LC Dorssers ◽  
MB van't Veer
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Peripheral Blood ◽  
Hodgkin’S Lymphoma ◽  
Lymph Node Biopsy ◽  
Stage I ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Sensitive Polymerase Chain Reaction

Abstract Stage I and II follicular non-Hodgkin's lymphoma (NHL) is clinically defined as a localized disease. To study the possibility that this disease is in fact disseminated, we used the sensitive polymerase chain reaction (PCR) method using translocation (14;18) as marker. Samples from 21 patients who were clinically diagnosed with stage I or II follicular NHL were analyzed for the presence of t(14;18)-positive cells using PCR. We analyzed (1) the diagnostic lymph node biopsy and (2) the peripheral blood or bone marrow samples from these patients. Translocation (14;18) cells were detected in the diagnostic lymph node biopsies of 12 patients. In 9 of these patients, t(14;18)-positive cells were detected in peripheral blood and/or bone marrow samples at diagnosis and/or after therapy. Thus, in 75% of the follicular NHL patients carrying the t(14;18) as a marker for lymphoma cells, t(14;18)- positive cells were detected in peripheral blood and bone marrow at diagnosis and after therapy. Our results show that t(14;18)-positive cells can be detected in the circulation of patients with stage I and II follicular NHL, indicating that, although diagnosed as localized, the disease is disseminated.

scholarly journals Strongly enhanced colorectal cancer risk stratification by combining family history and genetic risk score

2018 ◽  
Vol Volume 10 ◽  
pp. 143-152 ◽  
Author(s):  
Korbinian Weigl ◽  
Jenny Chang-Claude ◽  
Phillip Knebel ◽  
Li Hsu ◽  
Michael Hoffmeister ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Risk Stratification ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Colorectal Cancer Risk
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