bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 59: Optimization of high-throughput, high-depth, targeted single-cell DNA sequencing to pancreatic ductal adenocarcinoma
Authors: Zhang Haochen , Karnoub Elias-Ramzey , Chaligné Ronan , Masilionis Ignas , Makohon-Moore Alvin , Hong Jungeui , Iacobuzio-Donahue Christine 
Published: June 2022

Abstract
Purpose of study: Despite insights gained by bulk DNA sequencing of cancer it remains challenging to resolve “mixed signals”, i.e. the admixture of normal and tumor cells, and/or of distinct tumor subclones. Bulk sequencing of pancreatic ductal adenocarcinoma (PDAC) has been particularly problematic due to the high stromal content and resulting low tumor cellularity. Strategies to account for this have included laser capture microdissection yet this is a laborious process not amenable to high-throughput pipelines. We sought to develop and apply a high-throughput, high-depth, targeted single-cell DNA sequencing (scDNA-seq) method to account for these issues, including the ability to extract high quality genomic information from low purity and archival samples.
Experimental procedures: Bulk whole exome sequencing (WES) was performed on 29 biologically distinct samples. For single cell sequencing, we developed a custom panel containing 186 amplicons covering 93 genes that represent the most common germline and somatic targets reported in PDAC. Based on a commercially available system that enables automatic enzymatic and mechanical tissue disruption with integrated fluidic processes, we optimized a nuclei extraction workflow from frozen tissues that is highly compatible with downstream microdroplet-based single-cell encapsulation and library preparation. With it we generated scDNA-seq data from archival tissues of 15 PDAC patients at varying stages of the disease. Results were compared to that found in matched bulk sequencing data.
Summary of new, unpublished data and conclusions: 42 samples were analyzed by single cell sequencing. Our nuclei extraction workflow generated on average 2867 single cell libraries per sample at &gt;80X read depth. The single-cell results aligned well with matched bulk data in terms of the detection of key genetic variants and their variant allele frequency (VAF). We also identified additional driver variants not seen by WES, some with direct clinical evidence. Benefits of this workflow over preexisting methods are its speed of sample preparation, efficiency of sample use (particularly for small samples), flexibility by allowing for storage of excess extracted nuclei, and economy of scale. Together, these features support preparation of large numbers of cancer samples in a relatively short period of time.
Citation Format: Haochen Zhang, Elias-Ramzey Karnoub, Ronan Chaligné, Ignas Masilionis, Alvin Makohon-Moore, Jungeui Hong, Christine Iacobuzio-Donahue. Optimization of high-throughput, high-depth, targeted single-cell DNA sequencing to pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 59.
Abstract 5903: Polygenic risk scores for prediction of breast cancer in Korean women
Authors: Jee Yon Ho , Ho Weang-Kee , Park Sohee , Easton Douglas , Teo Soo-Hwang , Jung Keum Ji , Kraft Peter 
Published: June 2022

Abstract
Background: Polygenic risk scores (PRS) developed in large European GWAS have been shown to perform well in Asian women relative to PRS developed in smaller Asian studies. However, prospective validation of absolute risk prediction models combining lifestyle and PRS in Asian women is limited. We evaluate the calibration of four PRS developed using Asian or European training samples; two PRS were restricted to genome-wide significant SNPs (GRS-11ASN, GRS-136EUR) and two included sub-genome-wide significant SNPs (PRS-42ASN, PRS-209EUR).
Methods: For each PRS, we compared discrimination (area under the curve [AUC]) and calibration (expected-to-observed ratio [E/O]) of three absolute risk models among 41,031 women from the Korean Cancer Prevention Study-II Biobank: (i) a model using incidence, mortality, and risk factor distributions (reference inputs) among U.S. women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS.
Results: All Asian and European PRS improved risk prediction for breast cancer in Korean women (Qx: AUC=0.65, Qx+PRS-42ASN: AUC=0.68, Qx+PRS-209EUR: AUC=0.69 in Korean-based model for age less than 50). We found that the U.S.-based absolute risk models overestimated the risks for women age ≥50 years (PRS-42ASN: E/O=1.93, 95% CI=1.69, 2.19, PRS-209EUR: E/O = 1.92, 95% CI=1.69, 2.19). Our absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS.
Conclusions: Incorporation of PRS previously developed in Asian and European-ancestry populations can improve discrimination in Korean women. Our finding suggests that PRS may be useful for prioritizing individuals for targeted intervention on their lifestyle such as alcohol intake and obesity. Larger Asian training samples should improve PRS discrimination among Korean women. Further studies are needed to evaluate the value of incorporating additional information on factors into a model in ancestrally diverse populations.
Citation Format: Yon Ho Jee, Weang-Kee Ho, Sohee Park, Douglas Easton, Soo-Hwang Teo, Keum Ji Jung, Peter Kraft. Polygenic risk scores for prediction of breast cancer in Korean women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5903.
Abstract 5910: Exploration of genetic ancestry and socioeconomic status in the incidence of neuroblastoma: An ecological study
Authors: Jung Eun Mi , Johnson Rebecca A. , Hubbard Aubrey , Spector Logan G. 
Published: June 2022

Abstract
Although global differences in the incidence of neuroblastoma have been examined, the underlying mechanism has yet to be elucidated. Previous studies have suggested genetic ancestry and human development index (HDI) as contributing factors, but few studies have been conducted at the international level. Here, we aimed to examine whether the frequency of common genomic variation associated with neuroblastoma can affect its risk at the ecological level with consideration of the socioeconomic status of a population. Minor allele frequencies (MAFs) for 22 single nucleotide polymorphisms (SNPs) were abstracted from the Geography of Genetic Variants Browser. The number of incident neuroblastomas for each population was obtained from the Cancer Incidence in Five Continents series. Further, population pseudo-polygenic risk scores (pp-PRSs) were calculated as a sum of MAFs at the population level, each of which was weighted by effect sizes from prior studies. Negative binomial regression was used to estimate the incidence rate ratios (IRRs) and the 95% confidence intervals (CIs) to examine whether differences in MAFs across the population influence the risk of neuroblastoma, with and without adjustment for HDI and whether pp-PRSs can be a predictor of the risk of neuroblastoma. Overall, our results indicated that the neuroblastoma risk associated with variation in SNP frequency could not be differentiated from that of HDI at the ecological level. Additionally, pp-PRSs were not significantly associated with the risk of neuroblastoma (IRR: 0.99, 95% CI: 0.62—1.60). Further study using individual-level data is warranted to minimize the ecological fallacy in this study.
Citation Format: Eun Mi Jung, Rebecca A. Johnson, Aubrey Hubbard, Logan G. Spector. Exploration of genetic ancestry and socioeconomic status in the incidence of neuroblastoma: An ecological study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5910.
Abstract 5943: Association between the consumption of meat and carbonated drinks and early onset gastric cancer in Chilean patients
Authors: Parra Carol , Molina Graciela , Coo Carla , López Jessica , Martín María San , Siche Javiera , Carvajal-Carmona Luis 
Published: June 2022

Abstract
Gastric cancer (GC) is the 5th most frequent neoplasm and the 3rd cancer with the highest mortality according to GLOBOCAN. GC is often diagnosed in middle aged and elderly people, with a peak in incidence between 60 and 70 years old. In contrast, early-onset GC is the GC had a strong hereditary component. Associations of sporadic late onset-GC and dietary factors have been published but the role of nutritional factors in early onset GC is unknown. The aim of this study is to investigate the association between the intake of red meat, pork, processed meats and carbonated drinks in a group of early-onset GC. Our study was carried out in 19 Chilean early-onset GC patients, aged between 32 and 60 years, and 32 healthy age matched individuals from the same population. Through a survey of nutritional habits carried out retrospectively considering the stage prior to the diagnosis of GC, we determined the amount, type and frequency of ingestion of red meat, pork, processed meat and carbonated beverages. To measure the association an odds ratio and non-parametric association statistic tests were used. For the association of meat intake, we used the WHO recommendation (less than 70 g of meat per day) to classify the meat consumption levels in both groups. An odds ratio of 25.5 (4.8-135.4, p=8.3x105) was determined between the consumption of more than 70 g of meat per day in the early onset GC group vs the control group. Even though there are no international recommendations for carbonated drinks consumption levels, we found a higher carbonated drink consumption among cases (cases: Ave.= 180,7, SD= ±108,5 vs controls: Ave.=43,3, SD=±38,3. P=0033). In conclusion, our results shows significant associations between the consumption of red meat, pork, processed meats, and carbonated drinks in the risk of early-onset GC patients compared with the control group. Our findings, suggest that nutritional factors could play a role in the early GC presentation, acting in conjunction with low penetrance gene mutations. We will incorporate more early onset patients to the study group and do a sex matching for the control group to evaluate this possible confounding factor. We will also incorporate a late onset GC group. We think that nutritional factors could be an important factor to modulate genetic risk, even in early-onset patients. Beca Chile Postdoctorado 74190063 to GM.
Citation Format: Carol Parra, Graciela Molina, Carla Coo, Jessica López, María San Martín, Javiera Siche, Luis Carvajal-Carmona. Association between the consumption of meat and carbonated drinks and early onset gastric cancer in Chilean patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5943.
Abstract 5960: Blood-based extracellular vesicle biomarker test for detection of early-stage pancreatic cancer
Authors: Hinestrosa Juan P. , Lewis Jean M. , Balcer Heath I. , Kurzrock Razelle , Lippman Scott , Krishnan Rajaram 
Published: June 2022

Abstract
Pancreatic cancer is an almost uniformly lethal malignancy, in large part because is it rarely detected in its early, curable stages. We recently conducted a study to evaluate the use of proteins associated with extracellular vesicles (EVs) isolated using an alternating current electrokinetic (ACE) system for the early detection of pancreatic ductal adenocarcinoma. Because earlier detection of pancreatic cancer greatly improves outcomes, we sought to devise a blood-based test with high specificity for detecting early-stage PDAC based on identification of EV-bound biomarkers. EVs were purified from control or stage I-II pancreatic ductal adenocarcinoma (PDAC) patient plasma using an ACE microelectrode array. Following collection of EVs onto the electrodes, contaminating plasma elements were washed away, and the electric field was turned off to release EVs into buffer. The isolated EV/exosome samples were then tested using bead-based multiplex immunoassay kits to determine relative concentrations of biomarkers of interest. Sample cohorts were divided into a training set (controls, N=146; PDAC cases, N=33) to develop a logistic regression-based classification model, and a validation set (controls, N=139; PDAC cases, N=35) to generate a probability-based score for predicting the presence of PDAC. For the training set, the algorithm identified six protein biomarkers associated with the presence of stages I-II cancer in PDAC patient plasma, with a receiver-operating characteristic (AUC) of 0.997 (95% CI: 0.978-1.000) compared to control plasma samples. For the validation set, the algorithm had a sensitivity of 82.9% (95% CI: 67.3% - 91.9%) at a specificity of 99.3% (95% CI: 96.0% - 99.9%), generating an AUC = 0.978 (95% CI=0.954-0.995). The exosomal PDAC assay shows feasibility for developing minimally invasive liquid biopsies that allow low-risk, routine screening of high-risk patients. Those patients identified by the test would be able to undergo additional testing to determine if there is PDAC present. The additional screening and testing of these patients may increase the likelihood of curative treatment. Further work in large datasets is warranted.
Citation Format: Juan P. Hinestrosa, Jean M. Lewis, Heath I. Balcer, Razelle Kurzrock, Scott Lippman, Rajaram Krishnan. Blood-based extracellular vesicle biomarker test for detection of early-stage pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5960.
Abstract 5981: Single cell RNA sequencing uncovers high-plasticity cell state during tumor metastasis
Authors: Zhang Yu , Wong Ching Ngar , Gong Lanqi , Guan Xin-yuan , Ru Beibei , Liu Beilei 
Published: June 2022

Abstract
Cancer metastasis remains the key barrier for patient’s cure. Tumor metastasis initiating from a single disseminated cell into the invasive nodule in the foreign microenvironment is poorly understand. In this study, we established the intravenous injection pulmonary metastatic model followed by single-cell RNA sequencing of disseminating cells from mice lungs at different timepoints, we identified a cluster of SLPI-high esophageal squamous cell carcinoma (ESCC) cells that mediates the lung metastasis evolution and predicts worse overall survival of ESCC patients. GSEA analysis reveals that the SLPI-high subset is functionally associated with epithelial-to-mesenchymal transition and neutrophil activation during lung metastasis. Immune infiltration prediction from TIMER also confirmed that high SLPI is tightly correlated with more abundance of neutrophils in the ESCC tumor microenvironment. SLPI is reported to drive the metastasis progression through regulating the vascular mimicry. In the next step, further in-vitro and in-vivo studies is required to explore the role of SLPI in ESCC cells in promoting lung metastasis evolution. We identified a SLPI+ ESCC cells with high pluripotency that particularly initiates the metastasis process.
Citation Format: Yu Zhang, Ching Ngar Wong, Lanqi Gong, Xin-yuan Guan, Beibei Ru, Beilei Liu. Single cell RNA sequencing uncovers high-plasticity cell state during tumor metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5981.
Abstract 5984: MT1-MMP cooperates with TGF-beta receptor-mediated signaling to trigger SNAIL and induce epithelial-to-mesenchymal-like transition in U87 glioblastoma cells
Authors: Djediai Souad , Suarez Narjara Gonzalez , Joly-Lopez Zoé , Annabi Borhane 
Published: June 2022

Abstract
Transforming growth factor (TGF)-β triggers metastasis through epithelial-to-mesenchymal transition (EMT) to which a role for a membrane type-1 matrix metalloproteinase (MT1-MMP) has been associated. While EMT cooperates with MMP activity in glioblastoma multiforme, the molecular crosstalk between TGF-β signaling and MT1-MMP however remains poorly understood. Here, the existence of common EMT biomarkers, induced through TGF-β and MT1-MMP inducer Concanavalin A (ConA), was explored using RNA-seq analysis and differential gene arrays in human U87 glioblastoma cells. TGF-β and ConA triggered SNAIL and Fibronectin expressions in a dose-dependent manner. Those inductions were antagonized by the TGF-β receptor kinase inhibitor Galunisertib, the JAK/STAT inhibitors AG490 and Tofacitinib, and by the diet-derived epigallocatechin gallate (EGCG). Transient gene silencing of MT1-MMP prevented the induction of SNAIL by ConA and abrogated TGF-β-induced cell chemotaxis. Moreover, ConA induced STAT3 and Src phosphorylation suggesting these pathways to be involved in the MT1-MMP-mediated signaling axis that led to SNAIL induction. Our findings highlight a new signaling axis linking MT1-MMP to TGF-β-mediated EMT-like induction in glioblastoma cells, which process can be prevented by the diet-derived EGCG
Citation Format: Souad Djediai, Narjara Gonzalez Suarez, Zoé Joly-Lopez, Borhane Annabi. MT1-MMP cooperates with TGF-beta receptor-mediated signaling to trigger SNAIL and induce epithelial-to-mesenchymal-like transition in U87 glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5984.
Abstract 599: Identification of lymphocyte activation gene 3 binding peptides using phage displayed peptide libraries for cancer immunotherapy
Authors: Lee Seok-Min , Lee Byungheon 
Published: June 2022

Abstract
Treatment with immune checkpoint blockades against cytotoxic T lymphocyte associated protein-4, programmed cell death-1, and programmed death-ligand 1 is currently giving improved results to many cancer patients. Nevertheless, a significant proportion of cancer patients treated with immune checkpoint blockades are still largely unsatisfied with the benefits of these drugs. One of the reasons is that cancer cells also use other immune checkpoints such as lymphocyte activation gene-3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains, and T-cell immunoglobulin and mucin-domain containing-3. LAG-3 negatively regulates activated T cells. In this study, we screened phage displayed-peptide libraries for peptides that selectively bind to LAG-3. After five rounds of screening, we selected a candidate peptide and named it LAG3Pep. LAG3Pep preferentially bound to human LAG-3-transfected HEK 293T cells over mock-transfected cells and phorbol myristate acetate/ionomycin/chloroquine-stimulated Jurkat T cells over unstimulated cells. LAG3Pep also bound to splenocytes isolated from tumor-bearing mice, suggesting the reactivity across human and mouse LAG-3. Pull-down of Jurkat T cell lysates using biotin-labeled LAG3Pep yielded a protein band of LAG-3. A competition by the pre-treatment of Jurkat T cells with a LAG-3-blocking antibody inhibited the cell binding of LAG3Pep. In addition, LAG3Pep inhibited the binding of LAG-3 protein to THP-1 cells expressing HLA-DR, a well-known LAG-3 ligand. Moreover, LAG3Pep recovered IL2 production by stimulated Jurkat T cells, which were suppressed by fibrinogen-like protein 1, another ligand of LAG-3, in the culture medium of HepG2 tumor cells. These results show that LAG3Pep selectively binds to LAG-3 and has a potential as a LAG-3 blocker for cancer immunotherapy.
Citation Format: Seok-Min Lee, Byungheon Lee. Identification of lymphocyte activation gene 3 binding peptides using phage displayed peptide libraries for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 599.
Abstract 5998: Peroxiredoxin IV promotes progression of colorectal cancer
Authors: Thapa Pratik , Jiang Hong , Hao Yanning , Ding Na , Alshahrani Aziza , Zaytseva Yekaterina , Wei Qiou 
Published: June 2022

Abstract
Peroxiredoxin IV (Prx4) is a multifunction enzyme with a primary antioxidant role of reducing free radicals such as hydrogen peroxide and peroxynitrite. Literature review suggests that Prx4 upregulation in colorectal cancer is associated with higher tumor metastasis and shorter survival of patients. However, the function and mechanisms of Prx4 in cancer development are not well understood. The goal of this study is to validate the oncogenic role of Prx4 and to identify potential mechanisms of invasion and metastasis. Western Blot was performed to compare the expression of Prx4 protein in a normal colon cell line and seven colorectal cancer cell lines. shRNA mediated knockdown of Prx4 was performed in cancer cell lines with higher expression of Prx4. Stable vector control and Prx4 knockdown cells were used to perform Scratch Wound healing assay to compare the rate of migration. Transwell Matrigel invasion assay was performed using the same cell lines with 10% FBS containing-medium as chemoattractant. Vector control and Prx4 knockdown HCT116 cells were orthotopically implanted into the cecum wall of immunodeficient mice and humanely euthanized four weeks later. Prx4 expression is upregulated in colorectal cancer cell lines compared to normal colon cell line NCM356. Stable knockdown of Prx4 in HCT116 and RKO cell lines resulted in a significant decrease in migration and invasion rates of cancer cell lines in vitro compared to vector control. Orthotopic implantation of HCT116 vector control and Prx4 knockdown cells into cecum wall resulted in a lower metastasis rate to the liver and the lungs. We are currently conducting mechanistic studies to determine how the loss of Prx4 leads to a decrease in malignancy of colorectal cancer cell lines. Prx4 promotes colorectal cancer cell invasion and metastasis. Our study suggests Prx4 is a critical oncogenic protein that can be used as a therapeutic target for patients. This work was partially supported by the National Institutes of Health R01CA222596, Molecular Mechanisms of Toxicity Training Grant in Toxicology (T32ES07266), and American Cancer Society RSG-16-213-01-TBE.
Citation Format: Pratik Thapa, Hong Jiang, Yanning Hao, Na Ding, Aziza Alshahrani, Yekaterina Zaytseva, Qiou Wei. Peroxiredoxin IV promotes progression of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5998.