bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4157: Autosome instability and loss of chromosome Y in blood lymphocytes predict lung cancer risk
Authors: Sun Bing , Wang Ying , Kota Krishna , Shi Yaru , Makambi Kepher H. , Loffredo Christopher A. , Shields Peter G. , Harris Curtis C. , Zheng Yun-Ling 
Published: May 2015

Abstract
Background: Cancer cells are characterized by frequent chromosome aberrations (CA), which reflect defects of the underlying mechanisms that maintain genomic stability. Chromosome aberrations in peripheral blood lymphocytes has been shown to be associated with overall cancer risk in previous small studies. However, the relationship between types of chromosome aberrations in blood lymphocytes and lung cancer risk has not been well defined. In a case-control study of non-small cell lung cancer, we evaluated if CA in autosomes and sex chromosomes were predictive of lung cancer risk. Method: Chromosome aberrations were determined by G-banding analysis of metaphase chromosomes from short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between CAs and lung cancer risk. Results: Autosome instability (defined as CA in any of the 22 pairs of autosomes in &gt; 5% of the cells) was significantly associated with lung cancer risk among individuals who were &lt;= 67 years of age; adjusted odds ratio (OR) of 5.0 [95% confidence interval (CI) = 1.6 - 15.3]. There was no significant association between autosome instability and lung cancer risk in individuals who were older than 67 years of age. Loss of chromosome Y was significantly associated with an elevated risk of lung cancer among males; adjusted OR of 3.2 (95% CI = 1.2 - 8.8). This association appeared to be stronger in older males (&gt; 67 years of age) and in African American males. We observed no significant association between loss of chromosome X and lung cancer risk in both males and females. Conclusion: Autosome instability and loss of chromosome Y in blood lymphocytes were significantly associated with lung cancer risk. Analysis of chromosome aberrations in blood lymphocytes may be a promising tool for the identification of sub-population who are at high risk of developing lung cancer.
Citation Format: Bing Sun, Ying Wang, Krishna Kota, Yaru Shi, Kepher H. Makambi, Christopher A. Loffredo, Peter G. Shields, Curtis C. Harris, Yun-Ling Zheng. Autosome instability and loss of chromosome Y in blood lymphocytes predict lung cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4157. doi:10.1158/1538-7445.AM2014-4157
Abstract 4158: Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma from never smokers
Authors: Kim Han Sang , Ahn Jin Woo , Yoon Jung-Ki , Han Soo Min , Jang Hoon , Eun Sungho , Shim Hyo Sup , Kim Hyun Jung , Kim Dae Joon , Lee Jin G. , Lee Chang Young , Bae Mi Kyung , Chung Kyung Young , Kim Eun Young , Jung Ji Y. , Kim Se Kyu , Chang Joon , Kim Hye Ryun , Kim Joo Hang , Lee Ji Hyun , Bang Duhee , Cho Byoung Chul 
Published: May 2015

Abstract
Background: Lung adenocarcinoma is a highly heterogeneous disease with various etiologies, prognoses, and responses to therapy. Although genome-scale characterization of lung adenocarcinoma has been performed, somatic mutation analysis of never-smoker EGFR/KRAS/ALK-negative lung adenocarcinoma has not been comprehensively conducted.
Methods: Patients with lung adenocarcinoma were eligible if they were never smoker without EGFR/KRAS mutation and ALK rearrangement. Whole exome sequencing was performed using the Illumina HiSeq 2,000 platform. Candidate loci identified in whole exome sequencing were validated using hybridization capture method and Sanger sequencing.
Results: We present an analysis of whole exome sequencing data from 16 EGFR/KRAS/ALK-negative lung adenocarcinomas with additional 54 tumors in two independent cohort sets. We identified 27 genes potentially implicated in the pathogenesis of lung adenocarcinoma. In addition to targetable PI3K/mTOR signaling (TSC1, PIK3CA, AKT2) and receptor tyrosine kinase (RTK) signaling (ERBB4) genes, some of the genes including SETD2 and PBRM1 (chromatin remodeling), CHEK2 and CDC27 (cell cycle), CUL3 and SOD2 (oxidative stress), and CSMD3 and TFG (immune response) have not been previously highlighted in lung adenocarcinomas. In total (N=70), TP53 is the most frequently altered gene (11%), followed by SETD2 (6%), CSMD3 (6%), ERBB2 (6%), and CDH10 (4%). In pathway analysis, majority of altered genes were involved in cell cycle/DNA repair (P&lt;0.001), and cAMP-mediated protein kinase A signaling (P&lt;0.001).
Conclusions: Genomic makeup of EGFR/KRAS/ALK-negative adenocarcinomas in never-smokers was remarkably diverse. Impairment in cell cycle/DNA repair may be involved in tumorigenesis and therapeutic targets in lung adenocarcinoma.
Note: This abstract was not presented at the meeting.
Citation Format: Han Sang Kim, Jin Woo Ahn, Jung-Ki Yoon, Soo Min Han, Hoon Jang, Sungho Eun, Hyo Sup Shim, Hyun Jung Kim, Dae Joon Kim, Jin Gu Lee, Chang Young Lee, Mi Kyung Bae, Kyung Young Chung, Eun Young Kim, Ji Ye Jung, Se Kyu Kim, Joon Chang, Hye Ryun Kim, Joo Hang Kim, Ji Hyun Lee, Duhee Bang, Byoung Chul Cho. Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma from never smokers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4158. doi:10.1158/1538-7445.AM2014-4158
Abstract 4162: Circulating C-reactive protein and lung cancer risk: A nested case-control study in the Southern Community Cohort Study
Authors: Wu Jie , Zheng Wei , Wen Wanqing , Hargreaves Margaret K. , Blot William J. , Cai Qiuyin 
Published: May 2015

Abstract
Lung cancer is the leading cause of cancer deaths in the United States and many other countries. Cumulative evidence suggests that chronic inflammation may play an etiologic role in lung carcinogenesis. C-reactive protein (CRP), a circulating biomarker of systemic inflammation, has been associated with increased lung cancer risk in several retrospective and a few prospective studies. However, prior studies included only a small number of African Americans with lung cancer, a group with higher lung cancer incidence rates than other ethnic or racial groups. We conducted a nested case-control study to evaluate the association of pre-diagnostic circulating levels of CRP with subsequent risk of lung cancer using data and biological samples collected in the Southern Community Cohort Study (SCCS), a prospective cohort study, in which approximately 86,000 men and women aged 40-79 years, two-thirds of whom are African American, were recruited from 2002 to 2009. Plasma CRP levels in 396 incident lung cancer cases (258 African Americans and 130 Whites) were compared with 784 matched controls. Overall, baseline plasma CRP levels were 29.4% higher among participants who subsequently developed lung cancer than among those who remained free of the disease (geometric mean: 4.4 µg/ml vs. 3.4 µg/ml; P = 0.0015). This difference was seen primarily among African Americans (geometric mean: 4.1 µg/ml vs. 3.0 µg/ml; P=0.0026) and not among Whites (geometric mean: 5.0 µg/ml vs. 4.5 µg/ml; P=0.3613). In both African Americans and Whites, elevated risk of lung cancer was associated with high circulating levels of CRP. However, the association was only statistically significant among African Americans; adjusted odds ratios (ORs) for developing lung cancer increased from 1.0 to 1.46 (95%CI: 0.89-2.40); 1.52 (95%CI: 0.88-2.61), and 2.95 (95%CI: 1.77-4.93) with increasing quartiles of plasma CRP (P-trend = 0.0018). The findings from this study suggest that circulating CRP level is positively associated with prospective lung cancer risk among African Americans.
Citation Format: Jie Wu, Wei Zheng, Wanqing Wen, Margaret K. Hargreaves, William J. Blot, Qiuyin Cai. Circulating C-reactive protein and lung cancer risk: A nested case-control study in the Southern Community Cohort Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4162. doi:10.1158/1538-7445.AM2014-4162
Abstract 4170: Oncogenic activation of LMO2 by EGFR signaling regulates STAT3 phosphorylation and transcriptional activity in human glioma
Authors: Fu Jun , Koul Dimpy , Wu Shaofang , Zheng Siyuan , Verhaak Roel G. , Yung W.K 
Published: May 2015

Abstract
Glioblastoma multiforme (GBM) is a highly heterogeneous disease characterized by multiple genetic abnormalities. Amplification and mutation of the epidermal growth factor receptor (EGFR) gene represent signature genetic abnormalities occurred in over 60% of GBM. The successful application of EGFR-targeted therapy for the treatment of GBM is thus dependent on a thorough understanding of the intricate signal pathways cross-linkage that underlies the pathobiology of this disease. The LIM-domain only factor 2 (LMO2) gene is a crucial oncogene involved in hematopoietic development and leukemogenesis. Herein, we showed, from the TCGA GBM data, that LMO2 is highly expressed in EGFR-aberrant GBM samples and might serve as a downstream effector of EGFR signaling in GBM. Depletion of LMO2 expression impairs the maintenance of glioma cell proliferation in vitro and in vivo. In addition, EGFR signaling induces LMO2 nuclear translocation and enables LMO2 to form a triplex with EGFR and Signal transducer and activator of transcription 3 (STAT3). More importantly, LMO2 serves as a bridging molecule to promote the formation of EGFR/STAT3 complex and to enhance EGFR-mediated STAT3 Y705 phosphorylation upon EGF stimulation, which in turn up-regulates the expression of STAT3-responsive genes involved in the regulation of cell proliferation and tumor development. In conclusion, these findings reveal that LMO2 might serve as a critical effector of EGFR signaling in human glioma and highlight the essential function of LMO2 in EGF-stimulated STAT3 activation and tumorigenesis.
Citation Format: Jun Fu, Dimpy Koul, Shaofang Wu, Siyuan Zheng, Roel G. Verhaak, W.K Yung. Oncogenic activation of LMO2 by EGFR signaling regulates STAT3 phosphorylation and transcriptional activity in human glioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4170. doi:10.1158/1538-7445.AM2014-4170
Abstract 4176: Identifying analytes associated with poor prognosis in CRC
Authors: French Christi Lynn , Weaver Alissa 
Published: May 2015

Abstract
Cancer patients with undetectable micrometastases at the time of diagnosis are in danger of subsequent metastatic growth that worsens their outcome. Therefore, identification of these patients with latent metastases could reduce morbidity and mortality by helping physicians to choose whether to treat with an adjuvant therapy. In colorectal carcinoma (CRC), 20-30% of stage II patients will have a recurrence at a distant site after removal of the primary tumor. In order for cancer cells to metastasize, they must switch to an “invasive phenotype”. To identify molecular changes in cancer that drive invasion, our laboratory previously built a molecular network model of invasive subcellular structures termed invadopodia. Centrality and random walk analyses identified candidate signaling hubs that may control invadopodia formation or activity. To identify which of these hubs control invasion in specific cancers, we are mining reverse phase protein array (RPPA) data from publicly available human tumor datasets. In this study, we focused on analysis of RPPA data from TCGA in CRC patients, segregated by poor prognosis and good prognosis. We tested three different definitions of poor prognosis: recurrence, survival, and TNM status at diagnosis. We found several promising analytes that were significantly associated with each poor prognosis definition, and recurrence provided the best separation of good vs. poor prognosis. Interestingly, many of the analytes significantly associated with survival are involved in apoptosis. Additionally, we refined the analysis by using a subset of patients (stage I-II), which resulted in even better separation of good vs. poor prognosis. We identified several analytes that are already significantly associated with the invadopodia network (src kinase and PI 3-kinase). We also identified some potential new invadopodia regulators, such as Cox2. This method has potential both to improve CRC survival by identifying patients that need adjuvant therapy as well as identify novel drivers of invadopodia.
Citation Format: Christi Lynn French, Alissa Weaver. Identifying analytes associated with poor prognosis in CRC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4176. doi:10.1158/1538-7445.AM2014-4176
Abstract 4181: Accurate and fast detection and comparison of larger clinically relevant insertions and deletions
Authors: Hein Anne-Mette K. , Dekker Patrick , Joecker Anika , Boysen Cecilie , Thomson Naomi , Oester Bodil , Arens Anne , Knudsen Bjarne , Knudsen Thomas , Forsberg Roald 
Published: May 2015

Abstract
Larger somatic insertions and deletions in tumor samples are often of significant clinical impact. Many of them are cancer driver mutations and play an important role in drug treatment1.
Detecting the accurate breakpoints of larger insertions and deletions is often problematic and inaccurate. Furthermore, due to ambiguous positioning of them in the human genome, they are hard to compare with known deletions and insertions in publicly available databases.
Here we present a complete analysis workflow to accurate identify, filter and annotate larger insertions and deletions with information from publicly available databases such as COSMIC. We apply our pipeline on publicly available tumor/normal matched pair data from a patient with Massive Acinic Cell Carcinoma (A. Nichols et al. (2013) Case Reports in Oncological Medicine, Article ID 270362), which has not been investigated for larger insertions and deletions before. We show that we can identify insertions and deletions, which should be reported as part of the list of somatic variants, the authors have presented. Moreover, we will point out potential challenges and how to solve them while comparing own results to data in databases.
Citation Format: Anne-Mette K. Hein, Patrick Dekker, Anika Joecker, Cecilie Boysen, Naomi Thomson, Bodil Oester, Anne Arens, Bjarne Knudsen, Thomas Knudsen, Roald Forsberg. Accurate and fast detection and comparison of larger clinically relevant insertions and deletions. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4181. doi:10.1158/1538-7445.AM2014-4181
Abstract 4187: Splicing factors ESRP1/ESRP2 as regulators of endocrine resistance in breast cancer
Authors: Gokmen-Polar Yesim , Nellamraju Yaseswini , Gu Xiaoping , Janga Sarath C. , Badve Sunil S. 
Published: May 2015

Abstract
Deregulation of alternative splicing (AS) has been implicated in the development of drug resistance, tumor progression and metastasis. RNA-binding proteins (RBPs) as controllers of AS may act as master regulators of cellular behavior. Among the RBPs, we previously have shown that the expression of epithelial splicing regulatory proteins 1 and 2 (ESRP1 & ESRP2) have significantly elevated in cases with high Oncotype DX scores and in ERα-positive cells with acquired tamoxifen resistance (MCF-7/ LCC2) (SABCS 2013). This study seeks to identify genes and their splice variants that are regulated by ESRP1 & ESRP2 and could cause development of endocrine resistance. To identify alternatively spliced genes by ESRP1 & ESRP2 in endocrine resistance, we have performed a four step bioinformatics approach as follows: 1) Motif analysis to identify genes targeted by ESRP1 & ESRP2, 2) Comparison of differentially expressed genes in tamoxifen treated samples (GSE17700 and GSE17705) with genes targeted by ESRP1 & ESRP2 identified above, 3) Protein-protein interaction from BIOGRID and 4) survival data using publically available datasets (KM Plotter). Motif analysis identified 15,450 genes targeted both by ESRP1 (P&lt;3.39e-05) and ESRP2 (P&lt; 5.53e-05). 2212 of these genes were differentially expressed in tamoxifen treated cases. This set of genes was further categorized based on the ESRP1 & ESRP2 enhancer/ suppressor motifs ratio resulting in 1260 genes. Further collective analysis of survival data from KM plotter (P&lt;0.001) and number of protein-protein interactions (&gt;50) narrowed down 79 candidate genes that are associated with tamoxifen resistance. Some of the genes (AURKA, ERRB3, ESR2, EGFR, and MDM2) have been previously implicated in the de novo or acquired resistance to tamoxifen. Validation of splicing variants of these genes in human tumors is ongoing. Elevated expression of ESRP1 & ESRP2 and its target genes play an important role in the development of tamoxifen resistance and recurrence of ER+ breast cancer. ESRP1 & ESRP2 by affecting splicing have the potential to induce tamoxifen resistance via multiple genes and pathways. Targeting ESRP1 & ESRP2 may offer novel avenues for combating endocrine-resistance in breast cancer.
Citation Format: Yesim Gokmen-Polar, Yaseswini Nellamraju, Xiaoping Gu, Sarath C. Janga, Sunil S. Badve. Splicing factors ESRP1/ESRP2 as regulators of endocrine resistance in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4187. doi:10.1158/1538-7445.AM2014-4187
Abstract 4189: Discovery of a novel carcinoma-associated EF hand containing protein by mining the dark matter of the human proteome
Authors: Delgado Ana Paula , Brandao Pamela , Hamid Sheilin , Ven Wim Van de , Narayanan Ramaswamy 
Published: May 2015

Abstract
The human genome contains thousands of novel and uncharacterized proteins. These unknown genes are difficult to mine due to lack of adequate information. Hence, they remain largely untapped. Reasoning that new druggable targets for cancer can be discovered from these uncharacterized proteins, we have developed a protocol to mine these proteins for cancer relevance. Using various cancer-related databases, we have developed a database of uncharacterized ORF proteins. Numerous ORFs from this database offer druggable targets. To develop a proof of concept for mining these targets, we have chosen one target, C1ORF87 for detailed characterization. The C1ORF87 was analyzed using bioinformatics approaches for mRNA and protein expression, SNPs, LOH, protein motifs and domains and for gene network interactions. We have identified the C1ORF87 gene as a calcium binding protein with an EF-Hand motif. The EF-hand motifs are present in numerous calcium binding proteins, which exert a complex function in tumor growth and suppression. We show that the C1ORF87 gene is down-regulated in the lung and breast carcinomas and up-regulated in the liver carcinomas. Hematopoietic and neuronal tumors were largely negative. Its expression in select normal tissues suggests that the C1ORF87 may be a putative druggable gene. Our results suggest that the C1ORF 87 gene may play a significant role in specific carcinomas. We further demonstrate that the dark matter of the human proteome can be readily mined to predict putative cancer targets. Detailed characterization of the C1ORF87 gene will be presented.
Citation Format: Ana Paula Delgado, Pamela Brandao, Sheilin Hamid, Wim Van de Ven, Ramaswamy Narayanan. Discovery of a novel carcinoma-associated EF hand containing protein by mining the dark matter of the human proteome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4189. doi:10.1158/1538-7445.AM2014-4189
Abstract 4195: Peroxisome proliferator-activated receptor α is regulated by E2F1-induced miR-19a in a feedback loop in glioma progression
Authors: Zhang Junxia , Shi Yan , Wang Yingyi , Luan Wenkang , You Yongping 
Published: May 2015

Abstract
The peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor, which belongs to the super-family of steroid hormone receptor. To date, the biologic function of PPARα in human cancers is still controversial and needs further investigation. In our study, we explored the clinical feature, biological function and potential mechanism of PPARα in glioma. PPARα expression was significant lower in high grade tissues than low grade tissues in whole genome gene profiling of 158 glioma tissues. PPARα activation using fenofibrate inhibited glioma cells proliferation, invasion and aerobic glycolysis. Further, PPARα was a direct target of miR-19a and miR-19a was modulated by E2F1 at transcriptional level. Moreover, PPARα activation repressed E2F1 activation by modulating transcriptional complexes formed with E2F1 and pRB proteins. Finally, we confirmed PPARα/E2F1/ miR-19a feedback loop in vivo using nude mouse glioma xenograft and human glioma tissues. To our knowledge, it is first time to demonstrate that PPARα regulates glioma development by E2F1-induced miR-19a in a feedback loop and provide important clues for understanding the key roles of PPARα functional network in glioma.
Note: This abstract was not presented at the meeting.
Citation Format: Junxia Zhang, Yan Shi, Yingyi Wang, Wenkang Luan, Yongping You. Peroxisome proliferator-activated receptor α is regulated by E2F1-induced miR-19a in a feedback loop in glioma progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4195. doi:10.1158/1538-7445.AM2014-4195