bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3283: NDEx, the Network Data Exchange: Collaboration, publication and data sharing for cancer pathways
Authors: Pratt Dexter R. 
Published: August 2018

Abstract
Computable network models of pathway mechanisms, molecular interactions, and cellular function are widely developed and used in cancer genome analysis. Dissemination and reuse of networks, however, needs common data standards, facile access by visualization and analysis applications, mechanisms for pre-publication collaboration, and integration with the publishing process. We present NDEx, the Network Data Exchange, an online resource (www.ndexbio.org) that addresses these needs by providing a framework in which users can store, share, access, and disseminate networks. These networks can range from small pathways to large interaction data or to hierarchical cell models. NDEx is user-driven, where every researcher can be an author, easily creating publicly available network resources with full control of the data content and organization. Networks can range from standard resources disseminated by organizations to novel, up-to-date content from individual scientists. Collaborators can privately share their networks for review and reference or for integration in analysis workflows across multiple scripts and applications. Access to NDEx by an extensive API and client libraries supports network-enabled application development. Published networks can go beyond diagrams and static supplemental data, becoming immediately accessible and interactive. Integration with academic publishing is underway, facilitated by features such as anonymous access by reviewers and minting of DOIs for networks. NDEx breaks down barriers to scientific discourse involving networks, fostering collaboration within and between communities.
Citation Format: Dexter R. Pratt. NDEx, the Network Data Exchange: Collaboration, publication and data sharing for cancer pathways [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 3283.
Abstract 3292: Revisiting TCGA data identifies key genes in lung adenocarcinoma
Authors: Shi Jianxiang , Xing Mengtao , Luo Chenglin , Wang Xiao , Dai Liping , Zhang Jianying 
Published: August 2018

Abstract
Although the incidence rate of lung cancer has declined over the past few years, it remains the leading cause of cancer death worldwide. The Cancer Genome Atlas has provided invaluable resources for cancer research. The development of next generation sequencing technology and evolution of data analysis tools make it possible to interpret the underlying mechanism of oncogenesis. In current study, normalized FPKM data from 572 samples derived from patients with lung adenocarcinoma (LUAD) from TCGA was used to do weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with lung adenocarcinoma. Raw counts data was used to identify differentially expressed genes in LUAD by using DESeq2 in R (version 3.4.2). WGCNA results shows that magenta (r = 0.47, p &lt;0.001)), black (r = 0.40, p &lt;0.001)) and yellow (r = -0.88, p &lt;0.001) modules are top 3 modules that associated with LUAD and cancer stage. Gene Ontology over-representation analysis shows that genes in magenta modules are involved with transcript elongation; genes in black modules are enriched in cell meiosis related biological processes, including chromosome segregation, nuclear division, DNA replication and mitotic nuclear division et al; genes in yellow module are enriched in angiogenesis, leukocyte migration and hemostasis. It is noteworthy that genes in magenta and black modules are upregulated and in yellow modules are downregulated. GOLM1 and MUC4 in magenta module play certain roles in cancer development. Several genes in MEGA family, including MAGEA3, MAGEA6, MEGEA16 and MEGEA1, and IGF2BP1 in black module have been reported to be overexpressed in various kinds of tumors. However, whether these in silicon discovered genes can be used to distinguish LUAD from controls still needs to be further evaluated.
Keywords: lung adenocarcinoma; TCGA; gene expression analysis; bioinformatics; cancer biomarker
Citation Format: Jianxiang Shi, Mengtao Xing, Chenglin Luo, Xiao Wang, Liping Dai, Jianying Zhang. Revisiting TCGA data identifies key genes in lung adenocarcinoma [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 3292.
Abstract 330: BRCA1 and BLM helicase compensate for replication fork defects in the absence of 53BP1 protein
Authors: Sybouts Erin H. , Tonapi Sonal S. , Bishop Alexander J. 
Published: August 2018

Abstract
53BP1 is well-known for its involvement in DNA double strand break (DSB) repair, binding DNA and influencing choice of DSB repair. In S/G2 phases of the cell cycle, 53BP1 accumulates at DSBs, but can be removed by BRCA1, allowing end-resection and homology-directed repair (HDR) to occur. Without BRCA1, HDR is defective unless 53BP1 is also lost, in which case HDR can proceed. Such secondary mutation is relevant as a mechanism of acquired chemoresistance in BRCA1 deficient tumors. BRCA1 is also important for maintaining replication fork stability, particular for blocking end resection by MRE11a at a collapsed fork. We therefore set out to ask whether 53BP1 also plays a role in maintenance of fork stability and how this role relates to the role of BRCA1 at a collapsed fork. 53BP1 has been indicated to co-localize with collapsed forks and indeed we find that in its absence fork stability is compromised in a DNA2, but not MRE11a, dependent manner. With decreased fork stability in the absence of 53BP1 we observe increased HDR, indicating a role for BRCA1 to compensate for the lack of 53BP1 by promoting HDR. However, if both 53BP1 and BRCA1 are both necessary for fork stability, then there must be additional compensating mechanisms providing fork stability when both are absent. In fact, absence of both 53BP1 and BRCA1 results in better replication progression than when either 53BP1 or BRCA1 alone are absent. A third mechanism of fork stabilization was identified involving BLM; a RecQ helicase involved in dissolving homologous recombination intermediates, can facilitate fork restart and reverse fork regression. Additionally, BLM has been shown to interact with both 53BP1 and BRCA1, is found at stalled replication forks, and promotes BRCA1 recruitment to sites of DNA damage. Targeting BLM in cells with impaired 53BP1 and BRCA1 increases chemosensitivity to DNA damaging agents, supporting the redundant nature of these three proteins at stalled replication forks. Our findings indicate that targeting BLM may be an effective treatment for HDR defective cancers that have developed chemoresistance; with applicability to BRCA1 and homologous recombination deficient cancers, such as breast, ovarian, and Ewing sarcoma.
Citation Format: Erin H. Sybouts, Sonal S. Tonapi, Alexander J. Bishop. BRCA1 and BLM helicase compensate for replication fork defects in the absence of 53BP1 protein [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 330.
Abstract 3300: Network analysis of the human protein-protein interactome: Tumorigenic signaling mechanisms
Authors: Murray Diana , Begum Kamrun N. , Califano Andrea , Honig Barry 
Published: August 2018

Abstract
The dysregulated signaling responsible for tumor cell state implementation and maintenance has been shown to be mediated by the concerted action of master regulator (MR) proteins. Highly connected MR protein modules serve as “tumor checkpoints” by translating upstream genetic alterations into aberrant protein activity that drives pathophysiological cellular phenotypes. Direct pathways for information flow among MR proteins, and between individual MR proteins and their upstream modulators and downstream effectors, are largely unknown. The Prediction of Protein-Protein Interactions (PrePPI) database contains 1.4M predictions for ~85% of the human proteome; of these, ~300K are predicted to be physical, i.e. direct one-to-one, interactions.We apply network analysis concepts, as implemented in the R package igraph, to the PrePPI interactome to predict structural mechanisms underlying tumorigenic signal transduction. Shortest path and random walk with restart algorithms elucidate 1) physical interactions between MR proteins, 2) physical interactions that connect MR proteins that do not directly bind to each other, 3) upstream signaling proteins with recurrent and patient-specific mutations that physically interact with MR proteins, and 4) downstream cofactors and transcription factors that may be involved in effecting a dysregulated phenotype.Our analysis predicts that physical interactions fully connect BACH2, BCL6, IRF8, and SPIB, established germinal center MR proteins. 1) BACH2 and BCL6 are predicted to interact directly through their BTB/POZ domains; BTB domains are known to mediate heterodimeric protein-protein interactions. 2) Additional proteins, including IBTK, ANFY1, PAX7, ZEB1, GABPB1/B2, connect SPIB to BACH2 and to BCL6, in some cases through ankyrin repeats, which are structural protein-protein interaction motifs. Several of the PrePPI-predicted proteins, e.g. IBTK, ZEB1, GABP, have previously been implicated in B-cell biology. The possible implications of our analyses for a wide range of MR proteins modules will be presented.The computational prediction of physical protein-protein interactions within the regulatory architecture of a tumor cell is a powerful approach to discovering novel tumorigenic signaling mechanisms, formulating specific experimentally testable hypotheses of function, including compound mechanisms of action, and prioritizing novel drug targets.
Citation Format: Diana Murray, Kamrun N. Begum, Andrea Califano, Barry Honig. Network analysis of the human protein-protein interactome: Tumorigenic signaling mechanisms [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 3300.
Abstract 331: Therapeutic co-targeting of WEE1 and ATM has synergistic effects and contributes to downregulation of PD-L1 expression in pancreatic cancer
Authors: Jin Meihua , Nam Ah-Rong , Park Ji Eun , Bang Ju Hee , Bang Yung-Jue , Oh Do-Youn 
Published: August 2018

Abstract
Background: Currently, targeting DNA damage response (DDR) is one of strategies for new cancer drug development. DDR pathway involves DNA damage repair, cell cycle progression, apoptosis, and regulate the immune system. In pancreatic cancer (PC), one of the most fatal disease, TP53 mutation was found in approximately 78% of cases and BRCA pathway alteration including BRCA1, BRCA2, the ataxia telangiectasia mutated (ATM) and PALB2 was observed in 5% (germline) and 12% (somatic) of patients. The purpose of this study is to evaluate the DDR-targeting strategy using Wee1 inhibitor and ATM inhibitor in PC.
Methods: Using a total of 11 kinds of PC cell lines (AsPC-1, Capan-1, Capan-2, MIA PaCa-2, PANC-1, SNU213, SNU324, SNU410, SNU2822, SNU2913, and SNU2918), AZD1775 (Wee1 inhibitor) and AZD0156 (ATM inhibitor) were tested.
Results: AZD1775 significantly inhibited cell proliferation in all of the PC cell lines. AZD1775 monotherapy induced apoptosis and S phase arrest, and decreased Wee1/ p-wee1/ p-CDC2 expression. An increase of rH2AX and caspase-7 cleavage were occurred by AZD1775. When the cells were treated with AZD1775, upregulation of p-ATM was observed.
The combination of AZD1775 and AZD0156, the synergism was found. P-wee1 and p-CDC2 were downregulated more obviously in co-treated cells compared with monotherapy.
In some cells, PD-L1 was increased after AZD1775 treatment. Interestingly the combination of AZD1775 and AZD0156 synergistically reduced PD-L1 protein level in the cancer cells, especially in SNU213 and SNU2913 cells.
Conclusion: Therapeutic WEE1 and ATM co-targeting strategy demonstrated promising anti-cancer effect in pancreatic cancer cells. Moreover, this co-treatment blocked PD-L1 expression. Taken together, this supports further clinical development of DDR targeting strategy in pancreatic cancer.
Citation Format: Meihua Jin, Ah-Rong Nam, Ji Eun Park, Ju Hee Bang, Yung-Jue Bang, Do-Youn Oh. Therapeutic co-targeting of WEE1 and ATM has synergistic effects and contributes to downregulation of PD-L1 expression in pancreatic 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 331.
Abstract 3317: Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: A site-specific analysis
Authors: Mochizuki Daiki , Misawa Kiyoshi , Imai Atsushi , Kanazawa Takeharu , Mineta Hiroyuki 
Published: August 2018

Abstract
Staging and pathological grading systems are useful but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to determine the methylation status of eight GPCR-encoding genes in HNSCCs and its relationship to recurrence, survival, and clinical characteristics (e.g., tumor location and lymph node metastasis). All eight genes (NPFFR1, NPFFR2, HCRTR1, HCRTR2, NPY1R, NPY2R, NPY4R, and NPY5R) encode neuropeptide receptors and are in the Class A β subgroup. This study is the first to implicate neuropeptide receptors in the genesis of HNSCC. To identify potential prognostic markers, we examined the methylation status of eight neuropeptide receptor gene promoters in 231 head and neck squamous cell carcinomas. The NPFFR1, NPFFR2, HCRTR1, HCRTR2, NPY1R, NPY2R, NPY4R, and NPY5R promoters were methylated in 80.5%, 79.2%, 67.1%, 73.2%, 35.1%, 36.4%, 38.5%, and 35.9% of the samples, respectively. In a multivariate Cox proportional hazards analysis, the odds ratio for recurrence was 2.044 (95% confidence interval [CI], 1.323-3.156; P = 0.001) when the NPY2R promoter was methylated. In patients without lymph node metastasis (n = 100), methylation of NPY2R (compared with methylation of the other seven genes) best correlated with poor disease-free survival (DFS) (odds ratio, 2.492; 95% CI, 1.190-5.215; P = 0.015). In patients with oral cancer (n = 69), methylated NPY1R and NPY2R were independent prognostic factors for poor DFS, both individually and, even more so, in combination (odds ratio, 3.90; 95% CI, 1.523-9.991; P = 0.005). Similar findings were observed for NPY2R and NPY4R in patients with oropharyngeal cancer (n = 162) (odds ratio, 5.663; 95% CI, 1.507- 21.28; P = 0.010). The present study suggests that the methylation status of the NPY1R, NPY2R, and NPY4R genes is an independent indicator of DFS in patients with oral and/or oropharyngeal cancers. Our findings support the use of methylation markers in patient selection for adjuvant therapy after initial surgical treatment and may aid oropharyngeal cancer screening and surveillance programs. However, they are preliminary and hence need to be validated in larger and more homogeneous HNSCC patient cohorts.
Citation Format: Daiki Mochizuki, Kiyoshi Misawa, Atsushi Imai, Takeharu Kanazawa, Hiroyuki Mineta. Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: A site-specific analysis [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 3317.
Abstract 3327: Correlating blood-based DNA methylation markers and prostate cancer risk factors in African-American men
Authors: Kwabi-Addo Bernard , Moses-Fynn Emmauel , Tang Wei , Beyene Desta , Apprey Victor , Kanaan Yasmine 
Published: August 2018

Abstract
Background: Detection of prostate cancer at an early stage is key for successful treatment and improvement of outcome. However, the limitations of PSA screening are well recognized and therefore novel approaches to prostate cancer screening are necessary. We have investigated the clinical significance of DNA methylation in the blood serum of African-American men with prostate cancer.
Method: We used pyrosequencing to examine the promoter methylation for a panel of 8 genes in blood samples extracted from 91 prostate cancer cases and 91 noncancerous control cases.
Results: Seven of the 8-gene panel–RARβ2, TIMP3, SPARC, CDH13, LINE1, CYB5R2 and DRD2–tested achieved significant difference between the cancer cases when compared to control cases. The RARβ2 and TIMP3 demonstrated significant association of DNA methylation with age for all cases analyzed. Associations of methylation status and various clinicopathologic features and patient survival were evaluated: we observed significant inverse association of serum vitamin D levels in the cancer cases and DNA methylation of CDH13 and also an inverse correlation between TIMP3 and DRD2 methylation with supplementary vitamin D in the cancer cases. On the other hand, we observed a direct correlation between HIN1 methylation and serum vitamin D level. In addition, we observed a direct correlation between RARβ2 and Sparc methylation with PSA level in the control but not the cancer cases.
Conclusion: Promoter methylation occurred more frequently in the serum of patients with prostate cancer than noncancerous cases, suggesting that epigenetic markers in serum have potential for diagnosis of prostate cancer in AA men.
Citation Format: Bernard Kwabi-Addo, Emmauel Moses-Fynn, Wei Tang, Desta Beyene, Victor Apprey, Yasmine Kanaan. Correlating blood-based DNA methylation markers and prostate cancer risk factors in African-American men [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 3327.
Abstract 3329: A newly developed Septin9 gene methylation assay dectecting double DNA strands for screening of colorectal cancer
Authors: Liang Qiuju , Huang Zhengbin , Xu Qingwen , Xu Feipeng , Huang Wenwei , Xie Wenfang , Zeng Lei , Liu Jiasu , Yu De-Hua 
Published: August 2018

Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors and places an enormous burden on society. The US FDA approved the application of Epi proColon on 12 April 2016, and permitted the application of the Septin9 gene methylation assay as a CRC screening test for average-risk population over 50 years old. The effectiveness of methylated Septin9 for CRC detection has been reviewed in the newly published recommendation statement by US Preventive Services Task Force (USPSTF). The Septin9 gene methylation assay is more cost efficient with higher compliance than the stool DNA test, and has been proven to be an accurate, reliable, fast, and convenient molecular test. However, the currently FDA approved Epi proColon assay needs to perform triplicated PCR reactions for each sample which leads to high cost. In order to improve the sensitivity and specificity, simplify the operational procesure, and reduce cost, we have developed an new Septin9 gene methylation assay in which the specific sequences of both methylated DNA strands and control gene could be amplificated and detected in one reaction. We evaluated sensitivity, specificity, and clinical performance using plasma samples from colonoscopy negative individuals and CRC patients. The preliminary data showed that the sensitivity and specificity for CRC detection was 77.4%(41/53) ,97.8%(90/92) respectively. A large scale clinical study with more than 1000 subjects is currently in progress. In conclusion, we have developed a new Septin9 gene methylation assay detecting double DNA strands, which demonstrated improved performance for early detection of CRC in clinical setting.
Citation Format: Qiuju Liang, Zhengbin Huang, Qingwen Xu, Feipeng Xu, Wenwei Huang, Wenfang Xie, Lei Zeng, Jiasu Liu, De-Hua Yu. A newly developed Septin9 gene methylation assay dectecting double DNA strands for screening of colorectal 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 3329.
Abstract 3374: CRISPR/Cas9 mediated genome editing induces exon skipping by alternative splicing or exon deletion
Authors: Mou Haiwei , Smith Jordan , Peng Lingtao , Yin Hao , Moore Jill , Zhang Xiao-Ou , Song Chunqing , Sheel Ankur , Wu Qiongqiong , Ozata Deniz , Li Yingxiang , Anderson Daniel , Emerson Charles , Moore Melissa , Weng Zhiping , Xue Wen 
Published: August 2018

Abstract
CRISPR is widely used to disrupt gene function by inducing small insertions and deletions. Here, we show that some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions that delete exons. For example, CRISPR-mediated editing of β-catenin exon 3, which encodes an autoinhibitory domain, induces partial skipping of the in-frame exon and nuclear accumulation of β-catenin. A single sgRNA can induce small insertions or deletions that partially alter splicing or unexpected larger deletions that remove exons. Exon skipping adds to the unexpected outcomes that must be accounted for, and perhaps taken advantage of, in CRISPR experiments.
Citation Format: Haiwei Mou, Jordan Smith, Lingtao Peng, Hao Yin, Jill Moore, Xiao-Ou Zhang, Chunqing Song, Ankur Sheel, Qiongqiong Wu, Deniz Ozata, Yingxiang Li, Daniel Anderson, Charles Emerson, Melissa Moore, Zhiping Weng, Wen Xue. CRISPR/Cas9 mediated genome editing induces exon skipping by alternative splicing or exon deletion [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 3374.
Abstract 3386: The oncogenic role of CD133 in hepatocellular carcinoma
Authors: Ching Yick Pang , Chan Wing Lim 
Published: August 2018

Abstract
Liver cancer (hepatocellular carcinoma, HCC) is one of the most prevalent malignancies worldwide. Because of the late diagnosis of the disease, the prognosis of HCC patient is often undesirable. Cancer Stem Cell (CSC), which represents a subpopulation of cancer cells with stem-like properties, plays a critical role in tumorigenesis and contributes significantly to the relapse and chemo-drug resistance of cancers. The cell surface marker, CD133/Prominin-1, has been identified as a biomarker for CSC in various cancers, including HCC. To understand the role of CD133 in hepatocarcinogenesis, we expressed CD133 in HCC cells and showed that CD133 significantly promoted cell growth. Interestingly, our data also indicated that expression of CD133 led to chromosomal instability indicated by elevation of aneuploidy population and centrosome numbers in CD133 expressing cells. To understand the molecular mechanism, we observed that a putative tumour suppressor in HCC, called TAX1-binding protein 2 (TAX1BP2), which functions as a centrosome over-duplication suppresser, was downregulated by CD133. Taken together, these data suggest that CD133 plays an oncogenic role in HCC and may downregulate TAX1BP2 to promote chromosome instability, centrosome duplication and hepatocarcinogenesis.
Citation Format: Yick Pang Ching, Wing Lim Chan. The oncogenic role of CD133 in hepatocellular carcinoma [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 3386.