bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6493: Ethnic disparities in breast cancer survival in Guam
Authors: Badowski Grazyna , Teria Rodney , Dulana Louis , Aguon Cabrini , Wilkens Lynne , Shvetsov Yurii , Novotny Rachel , Guerrero Rachael T. Leon 
Published: April 2023

Abstract
Background: Breast cancer is the second leading cause of cancer-related death among women in Guam. The breast cancer mortality rate is higher in Guam than in the U.S. (27.3 vs 20.3 per 100,000 women, age-adjusted, 2013-2017 data); even though the incidence rate remains lower (86.6 vs 126.8 respectively). Guam has major ethnic disparities in breast cancer survival with CHamoru (indigenous people) and Micronesian (immigrants from other Micronesian Islands) faring much worse than other ethnic groups. The purpose of this study was to determine the survival rates of breast cancer patients in Guam and examine the effects of demographic and other mortality risk factors on breast cancer survival.
Methods: This study included 1105 women diagnosed with primary invasive breast cancer and reported to the Guam Cancer Registry from 1998-2020. Five-year and 10-year survival rates were calculated using the Kaplan-Meier method and were compared using the log-rank test across different ethnic groups: CHamoru (N = 528), Filipino (N = 336), Asian (N = 66), Micronesian (N = 51), and Caucasian (N = 71). The Cox proportional hazards regression was used to investigate the effects of age, year of diagnosis, ethnicity, breast cancer staging, and cancer treatment status on the risk of all-cause mortality.
Results: Mean age at diagnosis was 58.2 years. Significant differences in the 5-year and 10-year survival rates were found across ethnic groups. Micronesians had the lowest 5-year and 10-year survival rates (55.9% and 48.5%) followed by CHamorus (81.1% and 68.1%, respectively). All-cause mortality was higher among CHamoru (HR = 2.28, 95% CI: 1.65, 3.16) and Micronesian women (HR=5.33, 95% CI: 3.30, 8.61) compared with Filipino women after adjusting for age, year of diagnosis, staging, and cancer treatment status. All-cause mortality among White and Asian women was not statistically significantly different from that among Filipino women. Cancer staging also indicated significantly higher hazard rate for late-stage patients when compared to early-stage patients (HR = 3.62, 95% CI: 2.70, 4.85).
Conclusion: The analysis suggests significant differences in breast cancer 5-year and 10-year survival rates across different ethnic groups, with Micronesian women exhibiting the highest hazard rate among women in Guam.
Acknowledgement: This study was supported by the PIPCHE/U54 Grant (U54CA143728), a partnership between the University of Hawai'i Cancer Center and the University of Guam.
Citation Format: Grazyna Badowski, Rodney Teria, Louis Dulana, Cabrini Aguon, Lynne Wilkens, Yurii Shvetsov, Rachel Novotny, Rachael T. Leon Guerrero. Ethnic disparities in breast cancer survival in Guam. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6493.
Abstract 6508: Eclipse, an automated CRISPR platform for the large-scale generation of cell models
Authors: Deng Peter , Rowe Matthew , King Anna , Sailor Dana , Chair Antinea , Morell Montse , Sommer Andreia G. , Holden Kevin 
Published: April 2023

Abstract
Major advances in gene editing using CRISPR have improved accessibility for the creation of disease relevant in vitro models, allowing researchers to readily interrogate oncogenic driver mutations and elucidate novel targets to overcome challenges within cancer research such as drug resistance. Despite this, the rapid generation of disease relevant cell lines at the scale needed for successful and efficient therapeutic development remains challenging in part due to the sheer number of potential oncogenic driver mutations and cancer targets along with using traditional manual approaches. Specific challenges include: the efficient generation of gene knockouts and corresponding loss of protein; efficient knock-in of gene tags and single nucleotide variants; and controlling the zygosity of these genetic outcomes. To address these limitations, we describe the use of our automated, high throughput CRISPR editing platform, ECLIPSE, for the rapid generation of cell models such as immortalized cells and induced pluripotent stem cells. We leveraged our chemically modified synthetic sgRNAs, optimized nucleofection methods, and automated pipelines for the generation of CRISPR-edited cells at various scales to address the needs of researchers. This scale ranges from individual edited cell clones for drug target validation to the generation of hundreds of knockout cell pools in a ready-to-assay arrayed format for gene target identification in drug screening. The utilization of automated systems such as the ECLIPSE platform are critical catalysts for the rapid generation of engineered cell lines at relevant scales to address the challenges of cancer research.
Citation Format: Peter Deng, Matthew Rowe, Anna King, Dana Sailor, Antinea Chair, Montse Morell, Andreia G. Sommer, Kevin Holden. Eclipse, an automated CRISPR platform for the large-scale generation of cell models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6508.
Abstract 6514: Liquid biopsy for lung cancer based on extracellular vesicles
Authors: Hinestrosa Juan P. , Dhani Harmeet , Lewis Jean M. , Schroeder Gregor K. , Balcer Heath I. , Kurzrock Razelle , Billings Paul 
Published: April 2023

Abstract
Background Liquid biopsy approaches for lung cancer are becoming increasingly common for diagnosis, prognosis, and management of the disease. Of the Approximately 236K new lung cancer cases that will be diagnosed in 2023, over 70% of those will be regional or distant with diminished chances of curative resection. Therefore, highly sensitive and specific approaches for early detection are key for mortality reduction. Extracellular vesicles (EVs), a new class of blood-based cell-free biomarker, can be informative for the diagnosis of lung cancer at its earliest stages.
Methods A case-control cohort of blood plasma samples from 146 pathologically confirmed lung cancer cases (stage I = 90, II = 42, III = 14; median age = 63 yrs.) and 491 controls (median age = 58 yrs) was used in this study. EVs were isolated using a proprietary technology and the EV protein cargo was analyzed via immunoassay. A machine learning engine was employed to determine the most informative biomarkers and algorithm for differentiation between cases and controls in a detection setting.
Results Using a stratified cross-validation approach, we found a biomarker signature that yielded an AUC of 0.966 (95% CI: 0.949 - 0.979) with an overall sensitivity of 91.1% (CI: 85.4% - 94.7%) at a specificity of 91.0% (CI: 88.2% - 93.3%). By stage, the following sensitivities were obtained: stage I: 92.2%, stage II: 88.1%, stage III: 92.8%. The algorithm developed includes 13 EV-protein biomarkers using the adaptive boosted tree methodology.
Conclusions Our pilot study demonstrates utility of a blood-based approach that can detect lung cancer at early stages, when treatment can be more effective. By combining multiple EV protein signatures, it is possible to achieve high sensitivity and specificity. Independently collected cohorts including confounding conditions, such as benign lung nodules and COPD, are being evaluated for validation purposes to improve performance in clinical settings.
Citation Format: Juan P. Hinestrosa, Harmeet Dhani, Jean M. Lewis, Gregor K. Schroeder, Heath I. Balcer, Razelle Kurzrock, Paul Billings. Liquid biopsy for lung cancer based on extracellular vesicles. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6514.
Abstract 6526: Investigation levels of trace elements in breast cancer types using laser spectroscopic techniques
Authors: Ahmed Ola Sayed , imam hisham 
Published: April 2023

Abstract
Breast cancer (BC) is the 2nd leading cause of death from cancer in women. Women have a lifetime risk of breast cancer of around 31%, which makes it the first most common malignancy in women. Diagnosing cancer and classifying its types is a complex process that relies heavily on sample analysis. Early detection of cancer diseases is one of the important and main factors in determining treatment and saving many patients before the disease worsens and reaches dangerous stages. Alterations in the levels of trace elements have been observed in breast cancer (BC) patients. However, the relationships between these alterations and the metabolic and clinical consequences of BC are unknown. The aim of the present work is to study in vitro possibilities and the effectiveness of introducing an efficient optical spectroscopic technique such as LIBS for the identification types of breast cancer, as well as determining the disease grade and severity. The ultimate goal of this work is to investigate the concentrations of several trace elements in BC patients, and their relationships with the molecular subtypes of tumors. The atomic transition of the neutral element lines of Fe, Al, Na, Ca, K, V, Co and Pb was chosen to determine the trace element levels of four breast cancer types. We found that the measured average level of trace elements can differentiate between different types of breast cancer.
Citation Format: Ola Sayed Ahmed, hisham imam. Investigation levels of trace elements in breast cancer types using laser spectroscopic techniques [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6526.
Abstract 6527: Fusion genes as novel putative biomarkers for head and neck squamous cell carcinomas
Authors: Valerio Yabdiel A. Ramos , Van Wyk Hannah C. , Peguero Esther Peterson , Santiago Josué Pérez 
Published: April 2023

Abstract
Head and neck squamous cell carcinomas (HNSCC) are highly aggressive types of cancers with a complex molecular etiology of disease and consequently result in delayed clinical detection, poor prognosis, and limited treatment strategies. Fusion genes, a hallmark of cancer, may be targeted for early identification and treatment of HNSCC; however, studies characterizing fusion genes in HNSCC remain limited. Oral Human Papillomavirus (HPV) infection is a major cause of HNSCC and can also promote the acquisition of fusion genes due to the genomic instability induced by its integration. Here, we retrieved RNA-sequencing data from 36 HNSCC tumors (18 HPV+ and 18 HPV-, GEO Accession: GSE74956) to identify fusion genes using the STAR fusion algorithm in each sample. Statistical analyses were performed in R statistical software. A total of 10 fusion genes were identified in at least 4 of the samples regardless of HPV status. We identified 3 fusion genes that were present in at least 4 of the HPV+ tumors: PMS2P9-CCDC146, MACC1-AC005062.1, AC096711.2-RPL7AP28, and one solely present in HPV- tumors: CTSC-RAB38. The remaining 6 fusion genes were present in both HPV+ and HPV- tumors: TVP23C-CDRT4, AC009271.1-LINC01905, MIR205HG-AOPEP, SEPTIN7P2-PSPH, KRT5-KRT84, KANSL1-ARL17A. While 4 of the identified fusion genes had been previously associated with cancer, there were 6 novel identified fusion genes, in which one or both partner genes have been associated with different cancers. Additionally, the identified fusion genes may be a product of transcription read-through of neighbor genes. The fusion genes associated with HPV infection might explain biological disparities in HPV+ versus HPV- HNSCC and may be targets for the prevention and diagnosis of HNSCC. Future studies need to determine the functional impact of the identified fusion genes in HPV+ tumors.
Citation Format: Yabdiel A. Ramos Valerio, Hannah C. Van Wyk, Esther Peterson Peguero, Josué Pérez Santiago. Fusion genes as novel putative biomarkers for head and neck squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6527.
Abstract 6553: The development of homologous recombination repair deficiency (HRD) score methodology using WES data and its application in patient-derived xenograft models
Authors: Wang Jixin , Kinneer Krista , Zhong Wenyan , Lai Zhongwu 
Published: April 2023

Abstract
Homologous recombination repair deficiency (HRD) and mutations in genes involved with homologous recombination repair (HRR) are associated with sensitivity to platinum-based chemotherapy, topoisomerase 1 inhibitors and inhibitors targeting DNA repair pathway. Use of the Myriad HRD test for HRD determination in preclinical models is not feasible globally. To address this challenge, we developed an approach to generate HRD scores from whole exome sequencing (WES) data and applied it to assess HRD status in patient-derived xenograft (PDX) models.
We used python package CNVkit for segmentation and gene-level/allele-specific copy number calling with customized settings according to CNVkit documentation. The reference was constructed using the WES BED file and hg38 reference genome when there are no paired control samples available. Next R package scarHRD was used to determine the HRD score that is the sum of loss of heterozygosity (LOH), telomere allele imbalances (TAI), and large fragment migrations (LST). The method was applied to the WES of 25 Xentech triple negative breast cancer (TNBC) PDX models to derive HRD scores. The samples were also separately profiled using Myriad’s MyChoice CDx assay. The two scores showed moderate correlation with Pearson r = 0.56. However, when n = 6 PDX models with low coverages (average depth &lt;100x) were excluded, the Pearson r improved to r = 0.76. We also found that the absolute value of HRD score calculated by CNVkit/scarHRD is lower than that of Myriad HRD score.
Furthermore, we evaluated the genomic landscape in this cohort of TNBC PDX models for the selected genes of HRR pathway (BRCA1, BRCA2, ATM, BRIP1, PALB2, RAD51C, BARD1, CDK12, CHEK1/2, FANCL, RAD51B, RAD51D, RAD54L). Sixteen models found to carry HRR mutations, with ATM and BRCA1 mutations being the most common ones, being found in 9 and 5 of 25 models, respectively. Although HRRm positive (HRRm+) models have higher HRD score for both Myriad HRD score and HRD score generated with CNVkit/scarHRD approach, the association between HRR (HRRm+/HRRm-) and Myriad HRD (HRD+/HRD- defined by HRD threshold of 42) is not statistically significant (Fisher’s exact test p value = 0.1998, odds ratio=3.5), likely due to small cohort sizes.
These results suggest that combination of CNVkit and scarHRD for HRD score calculation may be an alternative approach for HRD identification in preclinical PDX models.
Citation Format: Jixin Wang, Krista Kinneer, Wenyan Zhong, Zhongwu Lai. The development of homologous recombination repair deficiency (HRD) score methodology using WES data and its application in patient-derived xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6553.
Abstract 6560: Identification of distinct patterns in diffuse large B-cell lymphoma through alternative splicing analysis
Authors: An Sanyeowool , Koh Youngil , Yoon Sung-Soo 
Published: April 2023

Abstract
Background Aberrant splicing in cancer cells contributes to cellular proliferation, escape from cell death, growth inhibition, invasion and metastasis, and immune escape. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, but the effect of AS on its pathogenesis has not been fully elucidated, so it is essential to find out DLBCL-specific splicing patterns and their potential as treatment targets.
Material and Method RNA-Seq dataset from DLBCL patients was retrieved from The Cancer Genome Atlas (TCGA) DLBCL (N=48) and Pan-cancer Analysis of Whole Genomes (PCAWG) DLBC (N=7) were used as the cancer group. In order to identify spliced genes that are significantly different from normal tissue, RNA-Seq data of normal lymphoid tissue produced in two studies of E-MTAB-513 (N=1) and E-MTAB-1733 (N=13) from the BioStudies were downloaded. Sequence reads were aligned to the GRCh38 reference genome using STAR aligner.
Results 5,470 genes identified as differentially spliced compared to normal in both rMATS and MAJIQ tools were studied. After sorting the AS events of these genes in order of highest average PSI value, events with an average PSI value of 0.7 or more in the top 2/3 samples and events with an average PSI value of 0.3 or less in the bottom 2/3 samples are selected. 8 exons of 7 genes were involved in Exon skipping (ES) events, 6 exons of 5 genes were involved in mutually exclusive exon (MXE) events, and an exon of a gene was involved in alternative 5' splice site (A5SS) Among these genes, exons 6 and 7 in CD53 showed high PSI values between exons 4 and 9. The average PSI values for exons 6 and 7 of CD53 in DLBCL were 0.923855 and 0.89096, respectively, which were significantly higher than the Normal group (p&lt;0.05). CD53 mediates IL-7R signaling and plays a role in the regulation of normal B-cell development. As a gene coding for cell surface protein, it is involved in various immune systems in T-cell and B-cell surfaces. In healthy tissue, transcripts that skip exon 5 and have a junction between exon 4 and exon 6 or 7 are not yet known and should be further studied. In addition, SLAMF8, which has an exon with a PSI value specific to DLBCL, is also involved lymphocyte activation and regulates B-cell receptor signaling.
Conclusion These DLBCL-specific patterns of selective exon usage are expected to be potential targets for cancer immunotherapy.
Citation Format: Sanyeowool An, Youngil Koh, Sung-Soo Yoon. Identification of distinct patterns in diffuse large B-cell lymphoma through alternative splicing analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6560.
Abstract 6561: Specific binding mode of RNA binding protetin FAM120A to lncRNA
Authors: Kawai Kenichiro 
Published: April 2023

Abstract
Long noncoding RNAs (lncRNAs) are defined as transcripts &gt;200 nucleotides in length with no protein-coding potential. LncRNAs play diverse roles in regulating gene transcription, post-transcription, translation, and epigenetic modification through interaction with RNA binding proteins (RBPs). Here, we analyzed binding motif of a RBP, family with sequence similarity 120A (FAM120A), which is highly expressed in multiple cancer types and associated with poor prognosis. To investigate FAM120A interacting RNAs genome-wide, we conducted cross-linking immunoprecipitation combined with deep sequencing (CLIP-seq) using an anti-FAM120A antibody in osteosarcoma cell line, U2OS. We identified 37,151 FAM120A-binding clusters by a peak detection algorithm. Up to 92% of these clusters were found within about 5,700 mRNAs, with the highest enrichment at 3'-UTRs. Interestingly, other clusters located within 959 lncRNAs, with peaks at 5’ and 3’ end. Fold enrichment analysis of CLIP reads in comparison with input reads revealed that FAM120A binds more preferentially to lncRNA than mRNA (median fold enrichments, 4.81 (lncRNA) versus 4.41 (mRNA), P&lt;0.001, Mann-Whitney U test). Motif analysis using the HOMER algorithm showed that FAM120A enriched sequence motifs in 3’ of mRNAs, 5’ and 3’ of lncRNAs were completely distinct. These results suggest that FAM120A may exhibit a motif-dependent selective binding to lncRNA in cancer cells. Given that RBPs bind to RNA molecules immediately after their transcription on chromatin, FAM120A may also selectively recognize RNA species and classify lncRNA and mRNA at the transcriptional stage. Since lncRNAs play pivotal roles in cancers FAM120A may exert oncogenic effects by the post-transcriptional regulation of a certain set of lncRNAs.
Citation Format: Kenichiro Kawai. Specific binding mode of RNA binding protetin FAM120A to lncRNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6561.
Abstract 6564: Biomarker discovery in triple negative breast cancer using RNA-sequencing analysis
Authors: Poulsen Jenna B. , Dobbs Mauri E. , Rapier-Sharman Naomi , Pickett Brett E. 
Published: April 2023

Abstract
Breast cancer is the most common form of cancer, and afflicted over 2.2 million people in 2020. The sheer volume of patients who suffer from breast cancer warrants continued research and discovery efforts to improve treatment options. Triple negative breast cancer (TNBC) affects 10-15% of breast cancer patients. Unlike other forms of breast cancer, TNBC does not have estrogen or progesterone receptors and makes little to none of the HER2 protein. Due to the lack of these biomarkers that are typical treatment targets for other kinds of breast cancers, the hormone therapies and drugs that target other breast cancers are often ineffective against TNBC. This leaves chemotherapy and radiation therapy as the main treatment options. Although chemotherapy and radiation have treatment benefits, the recurrence rate after treatment is around 40%. Furthermore, these treatment options are very detrimental to the body, resulting in a weaker patient and a necessary recovery time between treatments. In this study, we analyzed publicly available RNA-sequencing (RNA-seq) data to identify the upregulated and downregulated transcriptional mechanism(s) that play a role in TNBC compared to healthy breast tissue. The analysis of the RNA-seq data was completed with the Automated Reproducible Modular Workflow for Preprocessing and Differential Analysis of RNA-seq Data (ARMOR), which trims, maps, and quantifies the mRNA sequencing reads to the human transcriptome for each read. The ARMOR program identified more than 12,000 differentially expressed genes between TNBC and healthy breast tissue samples. We then applied an artificial intelligence-based classification method, a random forest algorithm, to identify new biomarkers that best differentiate TNBC cells from healthy cells. These specific transcriptional biomarkers for TNBC could potentially be used as diagnostic biomarkers or as therapeutic targets. We anticipate that this data may expand the treatment options for TNBC.
Citation Format: Jenna B. Poulsen, Mauri E. Dobbs, Naomi Rapier-Sharman, Brett E. Pickett. Biomarker discovery in triple negative breast cancer using RNA-sequencing analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6564.