bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3229: Prediagnostic biomarkers of metabolic dysregulation and cancer mortality
Authors: Akinyemiju Tomi 
Published: August 2018

Abstract
INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality.
METHODS: Prospective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), and adjusted for baseline covariates, including age, gender, income, education, physical activity, BMI, smoking status, alcohol use, and comorbidity score.
RESULTS: Among 1764 participants with available biomarker data, each SD higher log-leptin was associated with a 54% reduced risk of total cancer mortality (HR: 0.46, 95% CI: 0.23 – 0.92) and obesity-related cancer mortality (HR: 0.55, 95% CI: 0.39-0.79). Among Blacks only, each SD higher log-resistin was associated with a nearly 7-fold increased risk of cancer mortality (adjusted HR: 6.68, 95% CI: 2.10 – 21.21). There were no significant associations of adiponectin or Lp(a) and cancer mortality.
CONCLUSIONS: Leptin is involved in long-term regulation of energy balance, while resistin is involved in chronic inflammation and LDL production. These findings highlight the biological mechanisms linking metabolic dysregulation with cancer mortality, and the influence of resistin on cancer mortality only among Blacks suggests that this hormone may be a useful biomarker of racial differences in cancer mortality that deserves further study.
Citation Format: Tomi Akinyemiju. Prediagnostic biomarkers of metabolic dysregulation and cancer mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3229.
Abstract 3244: Enrichment of Helicobacter pylori mutant strains after eradication therapy analyzed by gastric wash-based quantitative pyrosequencing
Authors: Watanabe Yoshiyuki , Oikawa Ritsuko , Yamamoto Hiroyuki , Itoh Fumio 
Published: August 2018

Abstract
The eradication of Helicobacter pylori reduces the risk of gastric cancer. A clear understanding of the factors underlying mixed infection with multiple clarithromycin susceptible and clarithromycin resistant H. pylori strains is necessary to design more effective therapies against H. pylori. We aimed to assess how the abundance and prevalence of H. pylori strains vary after clarithromycin based eradication therapy. Using gastric wash samples, which represent the entire stomach, we sequentially analyzed the abundance and prevalence of H. pylori DNA by 23S ribosomal RNA pyrosequencing before and 1, 2, and 3 years after eradication therapy. Low levels of H. pylori DNA were still detectable at the first year follow up in all samples with negative post treatment urea breath test results. The abundance of H. pylori DNA decreased significantly until the 2 year follow up, but it switched to an increase at the 3 year follow up. Importantly, the ratio of the prevalence of mutant strains to the prevalence of wild type strains had already increased at the first year follow up and continued to increase, suggesting the selection and growth of clarithromycin resistant strains during the follow up periods. Being sensitive and representative, our assay will be useful in effectively addressing gastric cancer development by enhancing the long-term success of intervention strategies and consecutive surveillance for H. pylori eradication.
Citation Format: Yoshiyuki Watanabe, Ritsuko Oikawa, Hiroyuki Yamamoto, Fumio Itoh. Enrichment of Helicobacter pylori mutant strains after eradication therapy analyzed by gastric wash-based quantitative pyrosequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3244.
Abstract 3246: Association between colorectal cancer and red or processed meat among Korean diet: A molecular approach
Authors: Yang Mihi , Kim Jeongseon , Park Jong Y. 
Published: August 2018

Abstract
To study whether red or processed meat cause colorectal cancer in non- western population, we performed a pilot study in Korean people (N=30, case, 15 vs. control 15, mean of age=59.7 yrs) with biological monitoring of exposure and response biomarkers, i.e. metabolites of polycyclic aromatic hydrocarbons and heterocyclic amine (1-OHP, PhIP, and MeIQx), their DNA-adducts (dG-C8-MeIQx), and homocysteine, malondialdehyde (MDA), C-reactive protein and epigenetic alteration (5mC). The subjects also filled out daily consumption of food before diagnoses. As results, they averagely consumed 59.89 g/day and 2.47 g/day of red and processed meat, respectively. There were positive associations among consumption of Kimch(g), folate (ug) and fruits(g). The consumption of red meat was not associated with the cancer and the control even showed higher processed meat (g). From biomonitoring, the average levels of urinary 1-OHP, PhIP, and MeIQx, blood-dG-C8-MeIQx and 5mC were 0.13 ppb, 9.9 ppt, 14.63 ppt, 5.23 ppt/1.8 ug of DNA, and 5.3%, respectively. We found younger people more consumed processed meat or beverage and showed higher urinary levels of MeIQx than elderly people. The urinary levels of PhIP were negatively associated with folate consumption. The cases showed higher levels of LDL-cholesterol, homocysteine, urinary 1-OHP and dG-C8-MeIQx than controls. There were positive associations among levels of MeIQx, MDA, and 1-OHP. In addition, levels of dG-C8-MeIQx were positively associated with those of 1-OHP and total cholesterol. The levels of global methylation of 5mC (%) were higher in well done meat consumers than others. In conclusion, the Korean subjects might consume less volume of red or processed meat than western people. From questionnaire (FFQ), we could not find association between red or processed meat and colorectal cancer. However, biological monitoring showed the Korean colorectal cancer could be affected by red or processed meat, due to association with exposure or response biomarkers, particularly long term exposure biomarkers, such as dG-C8-MeIQx. This molecular epidemiological approach provides more reliable evidences to overcome limitation of case-control studies.
Citation Format: Mihi Yang, Jeongseon Kim, Jong Y. Park. Association between colorectal cancer and red or processed meat among Korean diet: A molecular approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3246.
Abstract 325: A functional homologous recombination assay predicts primary chemotherapy response and long-term survival in ovarian cancer patients
Authors: Tumiati Manuela , Hietanen Sakari , Hynninen Johanna , Pietilä Elina , Färkkilä Anniina , Kaipio Katja , Alkodsi Amjad , Tuominen Minna , Hautaniemi Sampsa , Carpén Olli , Kauppi Liisa 
Published: August 2018

Abstract
Background:
High-grade serous ovarian cancer (HGSOC) is the most common and aggressive type of ovarian cancer (OC) and the fifth most common malignancy occurring in women, meaning that 1 in 70 will develop OC during her lifetime. The current first-line treatment for HGSOC patients consists of cytoreductive surgery and platinum/taxanes-based chemotherapy. Homologous recombination deficiency (HRD) correlates with platinum sensitivity in OC patients, which clinically is the most useful predictor of sensitivity to PARPi. To date, there are no reliable diagnostic tools to anticipate response to platinum-based chemotherapy, thus we aimed to develop an ex vivo functional HRD detection test that could predict both platinum-sensitivity and patient eligibility to targeted drug treatments.
Methods:
We obtained a functional HR score by quantifying homologous recombination (HR) repair after ionizing radiation-induced DNA damage in primary ovarian cancer samples (n=24). Samples spontaneously clustered in 3 categories: HR-deficient, HR-low and HR-proficient. We analysed the HR score association with platinum sensitivity and treatment response, platinum-free interval (PFI) and overall survival (OS), and compared it with other clinical parameters (treatment strategy, FIGO stage, age). In parallel, we performed DNA sequencing of HR genes to assess if functional HRD can be predicted by currently offered genetic screening.
Results:
Low HR scores predicted primary platinum sensitivity with high statistical significance (p=0.001) and associated with longer PFI (HR-deficient vs HR-proficient: 531 vs 113 days). The HR score was the only factor that significantly correlated with improved OS (HR score &lt;35 vs ≥35, hazard ratio=0.12, 95% CI=0.02 to 0.79, p=0.026). At the genomic level, we identified a few mutations of unclear significance in HR genes but, overall, DNA sequencing failed to predict functional HRD.
Conclusions:
We developed an ex vivo assay that detects tumor functional HRD and an HR score able to predict platinum sensitivity, which holds the clinically relevant potential to become the routine companion diagnostic in the management of ovarian cancer patients.
Citation Format: Manuela Tumiati, Sakari Hietanen, Johanna Hynninen, Elina Pietilä, Anniina Färkkilä, Katja Kaipio, Amjad Alkodsi, Minna Tuominen, Sampsa Hautaniemi, Olli Carpén, Liisa Kauppi. A functional homologous recombination assay predicts primary chemotherapy response and long-term survival in ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 325.
Abstract 3270: Pan-cancer analysis of 1,962 whole-genomes reveals significantly mutated CTCF/cohesin insulators
Authors: Liu Eric Minwei , Martinez-Fundichely Alexander , Cuykendall Tawny , Dumelie Jason G. , MacKay Matthew , Dhingra Priyanka , Jaffrey Samie R. , Khurana Ekta 
Published: August 2018

Abstract
Recent studies have shown that mutations at non-coding elements, such as the TERT promoter and ESR1 enhancer, can act as cancer drivers. However, an important class of non-coding elements, namely CTCF/cohesin insulators, has been overlooked in the previous driver analyses. It is known that promoter and enhancer interactions are facilitated by partitioning of the human genome into DNA loops. These loops act as insulated neighborhoods preventing the interactions of enhancers and promoters across loops. They are held together by the binding of two CCCTCF binding factors (CTCF) and the cohesin complex, which consists of four core transcription factor subunits (SMC1, SMC3, RAD21 and either STAG2 or STAG1) at the loop ends. Disruption of the loop anchor regions, called CTCF/cohesin insulators, can lead to de novo enhancer-promoter interactions and subsequent dysregulation of associated genes. We used insulator annotations from cohesin ChIA-PET assays and analyzed somatic mutations in 1,962 whole-genomes from 21 cancer types. We find that the mutations predicted to disrupt DNA binding motifs of CTCF, RAD21 and SMC3 are enriched in many cancer types due to the sequence contexts of neutral mutational processes. Using a novel computational approach, CNCDriver (Cornell Non-Coding Driver), that balances the interplay between neutral mutational rate covariates of CTCF/RAD21/SMC3 motif loss and the stronger functional impact of motif-disrupting mutations, we identify the insulators that show signals of positive selection during tumor evolution. We find that the mutations in significantly mutated insulators are associated with differential expression of genes involved in multiple cancer pathways: TGF-β, Hedgehog and Wnt signaling. In particular, we find 16% of melanoma samples show mutations in an insulator that are associated with up-regulation of TGFB1, which is known to promote angiogenesis and tumor cell migration in melanoma. Thus, our study reveals insulators as a novel class of non-coding cancer drivers. Identification of significantly mutated insulators can complement the identification of other types of non-coding cancer drivers (promoters, enhancers and ncRNAs) to fully understand the role of non-coding alterations in tumorigenesis.
Citation Format: Eric Minwei Liu, Alexander Martinez-Fundichely, Tawny Cuykendall, Jason G. Dumelie, Matthew MacKay, Priyanka Dhingra, Samie R. Jaffrey, Ekta Khurana. Pan-cancer analysis of 1,962 whole-genomes reveals significantly mutated CTCF/cohesin insulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3270.
Abstract 3281: PDX Finder: An open and global catalogue of patient tumor-derived xenograft models
Authors: Conte Nathalie A. , Meehan Terrence F. , Begley Dale A. , Krupke Debbie M. , Halmagyi Csaba , Mason Jeremy C. , Mosaku Abayomi , Neuhauser Steven B. , Parkinson Helen , Bult Carol J. 
Published: August 2018

Abstract
Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, drug response and for tailoring chemotherapeutic approaches to individual patients. PDX models are produced and made available in repositories managed by small academic labs, large research consortia and contract research organizations. Because of the distributed and heterogeneous nature of PDX repositories, finding relevant models of interest to investigators is a challenge. To address this issue, The Jackson Laboratory and EMBL-EBI have co-developed the PDX Finder, a comprehensive open global catalogue of PDX models and their associated data across resources. In support this initiative, we coordinated the community initiative to develop the PDX models Minimal Information standard (PDX-MI) that defines the minimal information necessary for describing key elements of a PDX model including the clinical attributes of a patient's tumor, methods of implantation, host strain, and quality assurance methods used for model validation†. PDX-MI serves as the basis for PDX Finder's comprehensive search and attribute filtering options (e.g., tumor histology, molecular variant, drug response). Within PDX Finder, model attributes are harmonized and integrated into a cohesive ontological data model that supports consistent searching across the originating resources. From PDX Finder, direct links to these resources are provided to allow users to contact the relevant institution for model acquisition and further collaboration. PDX Finder is formally collaborating with several worldwide consortia including PDXnet and EurOPDX to increase “findability” of PDX models and to advance cancer research and drug discovery. PDX Finder is currently displaying over 1200 PDX models for a wide variety of cancers and is actively recruiting more models. The community is invited to explore and provide feedback on our portal as we build this rich resource at : www.pdxfinder.org.
† Meehan et al, 2017. PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models. Cancer Res. 2017 Nov 1;77(21):e62-e66.
Citation Format: Nathalie A. Conte, Terrence F. Meehan, Dale A. Begley, Debbie M. Krupke, Csaba Halmagyi, Jeremy C. Mason, Abayomi Mosaku, Steven B. Neuhauser, Helen Parkinson, Carol J. Bult. PDX Finder: An open and global catalogue of patient tumor-derived xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3281.
Abstract 3288: The landscape of circular RNA in cancer
Authors: Vo Josh N. , Zhang Yajia , Shukla Sudhanshu , Xiao Lanbo , Robinson Dan , Wu Yi-Mi , Gao Sisi , Engelke Carl , Cao Xuhong , Nesvizhskii Alexey , Chinnaiyan Arul 
Published: August 2018

Abstract
Circular RNAs (circRNAs) are an intriguing class of RNA due to their covalently closed structure, relatively high stability, and implicated roles in gene regulation. Here we used exome capture RNA-Seq, a non-poly(A) high-throughput RNA-sequencing protocol, to detect and characterize circRNAs across &gt;800 cancer samples. When compared against the two gold-standard methods (Ribo-Zero and RNase-R), capture sequencing significantly enhanced the enrichment of circRNAs and preserved accurate circular-to-linear ratios. We compiled the detected circRNAs from capture sequencing into the public OncoCirc database, the most comprehensive catalogue of circRNA species to-date. With this database, we identified the best circRNAs to serve as biomarkers for prostate cancer and were able to detect a novel class of circRNAs involved two genes. OncoCirc will serve as a valuable resource for the development of circRNA for diagnostic or therapeutic purposes for other cancers, as well as the study of circularization as an intriguing RNA splicing process.
Citation Format: Josh N. Vo, Yajia Zhang, Sudhanshu Shukla, Lanbo Xiao, Dan Robinson, Yi-Mi Wu, Sisi Gao, Carl Engelke, Xuhong Cao, Alexey Nesvizhskii, Arul Chinnaiyan. The landscape of circular RNA in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3288.
Abstract 3298: High-content phenotyping of somatic cancer mutations by functional variomics
Authors: Sahni Nidhi , Ng Patrick Kwok-Shing , Jeong Kang Jin , Mills Gordon B. 
Published: August 2018

Abstract
Cancer genomes are highly complex with numerous somatic mutations identified across patient populations. Previous studies on genomic mutations have shed light on new means for cancer therapeutic interventions. With rapid advances in next-generation sequencing, accumulating genotypic information in the absence of efficient and systematic functional analyses of genomic aberrations will create a bottleneck in understanding genotype-phenotype relationships in cancer. To address these challenges, here we report a systems-level functional variomics approach integrating high-throughput phenotyping with robust computational analyses to investigate mutation-specific effects. This systematic functional platform consists of massively parallel mutagenesis, sensitive survival assays using growth factor-dependent cell models, and functional network perturbation profiling of mutations on signaling effects. We profile several thousands of genomic aberrations, including point mutations, gene fusions and indels, and significantly expand the repertoire of characterized actionable mutations. This study represents a valuable resource and provides insights in prioritizing cancer-causing mutations, and uncovering patient-specific disease mechanisms at a high resolution, a critical step towards personalized precision medicine.
Citation Format: Nidhi Sahni, Patrick Kwok-Shing Ng, Kang Jin Jeong, Gordon B. Mills. High-content phenotyping of somatic cancer mutations by functional variomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3298.
Abstract 3312: Identification of tissue-of-origin in cancer of unknown primary site (CUPS) using methylation-specific targeted resequencing: A pilot study
Authors: Bae Jeong Mo , Kim Kwangsoo , Chae Hee Jun , Wen Xianyu , Kim Kang Yeol , Gwon Hwang Kwan , Cho Nam-Yun , Kang Gyeong Hoon 
Published: August 2018

Abstract
Purpose: Cancer of unknown primary site (CUPS) is a group of cancers for which the anatomic site of origin remains occult after detailed investigation. Until now, immunohistochemistry and tissue-specific RNA expression pattern have been used to predict tissue-of-origin in CUPS. However, these techniques do not fulfill the sensitivity and specificity for clinical practice. Recently, several studies found the tissue-specific methylation patterns in the genome. In this context, we tried to discover the tissue-specific methylation markers by analyzing genome-wide methylation data in The Cancer Genome Atlas (TCGA). Then, we aimed to develop the methylation-specific next-generation sequencing panel that predicts the tissue-of-origin in CUPS by validating panels in clinical samples.
Experimental Design: We selected every 17 mostly hypermethylated CpG sites in 31 cancer types by analyzing 8,350 cases of Infinium 450K methylation data in TCGA. With the selected 527 CpG sites as input variables, we constructed 465 decision tree models for all pairwise classification of 31 cancer types by using C50 package in R. Based on the two class classification models, we implemented an ensemble voting classifier for tissue-of-origin prediction test in fresh frozen tissue of 50 primary cancers of 8 tissue types using methylation-specific next-generation sequencing, which targeted 527 tissue-specific CpG sites by post-bisulfite method.
Results: In in silico analysis, we randomly selected 80% of the TCGA data for training decision tree models and used the remaining 20% of the data for testing those models. The sensitivity and specificity for the tissue-of-origin in 31 cancer types of testing data were 0.91 and 0.99 in decision tree models, respectively. In methylation-specific next-generation sequencing, our model predicted 40 cases (80%) of total 50 clinical samples, successfully.
Conclusions: Prediction of tissue-of-origin using methylation-specific next-generation sequencing might be promising. For clinical application, further study using more comprehensive targeted resequencing panel using formalin-fixed, paraffin-embedded tissues will be followed.
Citation Format: Jeong Mo Bae, Kwangsoo Kim, Hee Jun Chae, Xianyu Wen, Kang Yeol Kim, Hwang Kwan Gwon, Nam-Yun Cho, Gyeong Hoon Kang. Identification of tissue-of-origin in cancer of unknown primary site (CUPS) using methylation-specific targeted resequencing: A pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3312.