bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4375: Complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas
Authors: Peng Dunfa , Guo Yan , Chen Heidi , Zhao Shilin , Washington Kay , Hu Tianling , Shyr Yu , El-Rafai Wael 
Published: July 2017

Abstract
Background: The incidence of Barrett’s-related esophageal adenocarcinoma (EAC) is rapidly rising in the USA and the Western countries. However, the interaction between genomic and epigenomic alterations in regulating gene expression networks in EAC is poorly understood.
Results and Discussion: We carried out an integrative analytical approach to identify DNA copy number, promoter DNA methylation and gene expression in a panel of esophageal adenocarcinomas, using chip-based technologies. Our analysis displayed significant differences between EAC and normal samples in DNA copy numbers, gene expression, and DNA methylation profiles. Our results identified remarkable incidence of DNA copy number (CN) alterations showing that 90% of probes had a copy number aberration (gain or loss) in at least one tumor, suggesting a vast chromosomal instability in EAC. Integrative analysis indicated that altered expression of 1755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes (56 overexpressed and 28 down regulated) were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, we detected a prominent K-RAS signature in EAC. Network analysis predicted activation of several important transcription factor networks in EAC, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. 56 genes were overexpressed in EAC with simultaneous promoter hypomethylation and gene amplification, including CDH17 and GATA6. Notably, several genes associated with inflammation such as COX2, IL8 and IL23R were overexpressed and hypomethylated in EAC, a reaffirmation of the underlying inflammatory process in Barrett’s tumorigenesis and a suggestion of an epigenetic regulation of these genes.
Conclusions: In summary, our integrative analysis of genetic and epigenetic alterations in EAC demonstrates a complex interaction between molecular mechanisms in EAC and provides several novel insights for future studies.
Citation Format: Dunfa Peng, Yan Guo, Heidi Chen, Shilin Zhao, Kay Washington, Tianling Hu, Yu Shyr, Wael El-Rafai. Complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4375. doi:10.1158/1538-7445.AM2017-4375
Abstract 4377: EBV associated gastric cancer in Korean
Authors: Lee Woochan 
Published: July 2017

Abstract
Gastric cancer was the third leading cause of death worldwide and most prevalent malignant cancer in Korea, comprising 20.8% of all cancers. The Cancer Genome Atlas (TCGA) divided gastric cancer to four subgroups; EBV (Epstein-Barr Virus infected, 9%), MSI (Microsatellite instability, 22%), GS (Genomically stable, 20%), CIN (Chromosomal instability, 50%). We sequenced transcriptomes of 11 gastric cancers associated with EBV infection (EBVaGC) tissues, 11 gastric cancers not associated with EBV infection (EBVnGC) tissues and 22 matched normal gastric mucosa for find unique features of Korean EBVaGC. We compared RNA expression, EBV gene expression, germline mutations, and somatic mutation between EBVaGC and EBVnGC. We found IKBKE gene, which is taking an essential role in regulating antiviral signaling pathways, expressed higher on EBVaGC tumor than EBVnGC tumor (p-value=1.73 x 10-4). While most EBV genes appeared to be similar, BMRF1,2 genes made distinctive patterns compared to previous TCGA report in expression of EBV which integrated into human cells. The BMRF-2 gene is associated with cell-to-cell spread of EBV, which is major infection mechanism of EBV. We found novel germline mutations on PABPC3, PGA3, and C4A,B in almost every samples, which are candidate for Korean specific mutations.
Citation Format: Woochan Lee. EBV associated gastric cancer in Korean [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4377. doi:10.1158/1538-7445.AM2017-4377
Abstract 4392: Genetic diagnosis of multiple hepatocellular carcinoma
Authors: Midorikawa Yutaka , Yamamoto Shogo , Tatsuno Kenji , Ueda Hiroki , Tsuji Shingo , Nagae Genta , Takayama Tadatoshi , Aburatani Hiroyuki 
Published: July 2017

Abstract
Multiple hepatocellular carcinoma (HCC) is categorized into two types; multicentric hepatocarcinogenesis (MC) and intrahepatic metastasis (IM). Although discrimination of the types of multiple HCC is of clinical importance, it is quite difficult to determine it correctly even after histological diagnosis. In order to determine multiple HCC as MC or IM, we compared pairs of multiple HCC samples from 40 patients with multiple HCC and 2 patients with pairs of primary HCC and extrahepatic metastasis such as adrenal grand and lung metastasis with regard to molecular aberrations. Exome sequence showed that more than 70% of somatic mutations were common in the pairs of IM, which were consistent with the result of a pair of primary HCC and extrahepatic metastasis, while no common somatic mutations was detected in genomic-MC (gMC) pairs. Notably, more than 60% of clinically metachronous-MC cases were diagnosed as genomic-IM (gIM) due to the concordance of mutation and shows significantly frequent tumor thrombus, suggesting that gIM pairs developed from the common ancestor. In addition, cell-free DNA was analyzed using exome sequence in five patients with recurrent HCC, and found that somatic mutations of cell free DNA were similar to the primary HCC only in gIM but not in gMC cases. Taken together, comparison of mutations in a pair of HCCs makes it possible to classify multiple HCCs into MC and IM, which is difficult to be correctly determined in clinical practice. Furthermore liquid biopsy for mutation analysis is available to make treatment plans for multiple HCC patients.
Citation Format: Yutaka Midorikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shingo Tsuji, Genta Nagae, Tadatoshi Takayama, Hiroyuki Aburatani. Genetic diagnosis of multiple hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4392. doi:10.1158/1538-7445.AM2017-4392
Abstract 4415: Fatty acid synthase-mediated palmitate production impacts epidermal growth factor receptor signaling to regulate specificity protein 1 in breast cancer cells
Authors: Barlow Lincoln J. , Zhang Jian-Ting 
Published: July 2017

Abstract
Fatty acid synthase (FASN), the sole cytosolic enzyme responsible for de novo palmitate synthesis, is critical for cancer cell survival and is a marker of poor prognosis. FASN overexpression has been shown to confer resistance to both drug and radiation resistance by inhibiting drug-induced ceramide production and by increasing DNA repair activities. Recently, it was found that FASN upregulation of non-homologous end joining (NHEJ) repair of double strand DNA breaks was due to FASN up-regulation of Poly (ADP-ribose) polymerase 1 (PARP1) by increasing expression of specificity protein 1 (SP1). However, how FASN regulates the expression of SP1 remains unknown. In this study, we tested the hypothesis that, palmitate, the end product of FASN catalysis, plays an important role in regulating SP1 expression by posttranslationally modifying epidermal growth factor receptor (EGFR) and affecting its activity. Using paired isogenic cell lines with FASN overexpression and FASN knockdown as well as exogenous supplementation of palmitate, we found that depleting palmitate in culture reduced SP1 expression while supplementing palmitate rescues this effect. Furthermore, FASN overexpression and knockdown increased and decreased, respectively, phosphorylation and activation of EGFR. Treatment with EGFR inhibitor, Erlotinib, reduced SP1 expression. These findings suggest that FASN regulation of SP1 and NHEJ repair may be via regulating EGFR activity. We are in the process of determining the potential effect of palmitoylation of EGFR on its activation and regulation of SP1 expression.
Citation Format: Lincoln J. Barlow, Jian-Ting Zhang. Fatty acid synthase-mediated palmitate production impacts epidermal growth factor receptor signaling to regulate specificity protein 1 in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4415. doi:10.1158/1538-7445.AM2017-4415
Abstract 4422: Capsaicin suppresses pancreatic tumor growth by inhibiting tumor cell metabolism
Authors: Ramachandran Sharavan , Srivastava Sanjay K. 
Published: July 2017

Abstract
Tumor cell metabolism is considered to be a hallmark of tumorigenic progression. Pancreatic cancer cells are shown to develop addiction towards the metabolic pathways like glycolysis and mitochondrial respiration to meet energy demands. Pancreatic tumor cells predominantly utilize cytosolic aerobic glycolysis for energy production. In our previous studies, we have reported that capsaicin treatment inhibits the survival of AsPC-1 and BxPC-3 pancreatic cancer cell lines. In this study, we evaluated the effect of capsaicin on glycolysis and mitochondrial respiration in pancreatic cancer cells. Our results showed that capsaicin treatment reduced the extra-cellular acidification rate (glycolysis) and oxygen consumption rate (mitochondrial respiration) in AsPC-1 and BxPC-3 cells in a concentration-dependent manner after 24h of treatment. Capsaicin treatment caused 86% and 55% down-regulation of glycolysis process in AsPC-1and BxPC-3 cells respectively. Our results also indicate the inhibition of glycolytic capacity and glycolytic reserve by capsaicin treatment indicating the potential of capsaicin to inhibit glycolysis. In addition, capsaicin treatment reduced 98% of basal oxygen consumption rate and ATP production in AsPC-1 cells. Furthermore, capsaicin treatment inhibited spare respiratory capacity & proton leak in a concentration dependent manner in AsPC-1 cells. Treatment of AsPC-1 and BxPC-3 with capsaicin for 48h also inhibited the expression of LDH-A and its upstream regulators such as HIF-1α, pSTAT3 (Y705) and EGFR as evaluated by Western blot. Our study thus indicate that capsaicin suppresses pancreatic tumor growth by down-regulating glycolysis and mitochondrial respiration. Further mechanistic studies are in progress. [Supported in part by R01 grant CA129038, awarded to (S.K.S.) by the National Cancer Institute].
Citation Format: Sharavan Ramachandran, Sanjay K. Srivastava. Capsaicin suppresses pancreatic tumor growth by inhibiting tumor cell metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4422. doi:10.1158/1538-7445.AM2017-4422
Abstract 4436: Novel microRNA signature score to predict bone metastasis and prognosis of breast cancer
Authors: Kawaguchi Tstutomu , Yan Li , Qi Qianya , Liu Song , Takabe Kazuaki 
Published: July 2017

Abstract
Backgrounds: 40,000 US women still die with breast cancer every year. Vast majority of death occur after they develop metastasis, where bone is the most frequent site for breast cancer. New measures to identify the patients who develop metastasis allow us to intervene early, which is expected to prolong survival. The aim of this study is to establish a microRNA (miRNA) signature scoring system that can predict bone metastasis and survival utilizing integrated transcriptomics analyses in breast cancer.
Materials and Methods: Both clinical and RNA expression data, including microRNA and mRNA, of 1051 patients were retrieved from The Cancer Genome Atlas (TCGA). 1) Multivariate Cox proportional hazard model and Kaplan-Meier for overall survival were performed to construct and identify novel models of miRNAs signature for predicting patient survival. 2) Competing risk analysis using the miRNAs signature was conducted to clarify its association with metastatic distributions. 3) Gene Set Enrichment Analysis (GSEA) was performed to identify the genome-epigenome significance of the miRNAs signature.
Results: 1) Utilizing Cox model on TCGA cohort, we established a novel risk scoring system with three miRNAs signatures (miR-19a, miR-93, and miR-106a) that identified the patients population with extremely poor overall survival (p = 0.0004; 5-y survival rate, 49.2%). This result was reproduced in two other completely independent cohorts with microarray datasets (GSE19536, p = 0.0009; GSE22220, p = 0.0003, respectively). 2) Utilizing competing risk analysis for each metastatic sites of breast cancer, we found that the patients with bone metastasis demonstrated significantly high scores (p = 0.0052). The evaluation also showed a statistical tendency of association with lung metastasis (p = 0.0854). 3) We found that high score is associated with several critical gene sets such as angiogenesis (p &lt; 0.0001) or epithelial mesenchymal transition (p = 0.0155) by GSEA that suggests that high signature score is associated with enhanced metastasis in breast cancer patients.
Conclusions: We established a miRNAs signature scoring system to predict bone metastasis and poor overall survival in breast cancer using novel integrated transcriptomics concept.
Citation Format: Tstutomu Kawaguchi, Li Yan, Qianya Qi, Song Liu, Kazuaki Takabe. Novel microRNA signature score to predict bone metastasis and prognosis of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4436. doi:10.1158/1538-7445.AM2017-4436
Abstract 4439: The urine miRNA transcriptome of prostate cancer is temporally stable and predicts disease aggressivity
Authors: Jeon Jouhyun 
Published: July 2017

Abstract
The clinical management of prostate cancer is the most common non-skin male malignancy in the world is hindered by the limitations of current diagnostic and prognostic tests, such as the low specificity of prostate-specific antigen (PSA) testing, low sensitivity of digital rectal examination (DRE) and complications of biopsies. To try to resolve these issues, we evaluated miRNA abundance in the urine of prostate cancer patients. Alterations in miRNA abundance levels have been reported as playing essential roles in the pathogenesis of cancer and is occurred in a tumor phenotype-specific manner (e.g. aggressive and non-aggressive). miRNAs are stable under diverse analytical conditions and can be detected in various types of body fluids including urine. These characteristics make them as promising non-invasive biomarkers. Here, we examined the intra- and inter-individual variance of urine miRNA abundance by investigating longitudinal changes over months to years in a cohort of patients with localized prostate cancer. We observed a large dynamic range of intra-individual variance in miRNA abundances and identified a set of miRNAs that is stable within individuals, and is biased toward specific biological functions including regulation of transmembrane channel activity. We combined this observation with machine-learning techniques to create a predictive model that can identify aggressive prostate cancer. This four miRNAs predictive model was validated in an independent prostate cancer cohort to non-invasively predict high-risk disease. Remarkably it showed comparable performance to the best existing tissue-based prognostic markers. These results demonstrated that non-invasive biomarkers can be developed to precede or supplement tissue-based tests by understanding the intra- and inter-tumoural heterogeneity of the urine miRNA transcriptome.
Citation Format: Jouhyun Jeon. The urine miRNA transcriptome of prostate cancer is temporally stable and predicts disease aggressivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4439. doi:10.1158/1538-7445.AM2017-4439
Abstract 4440: New predictive and preventive biomarkers for preclinical hepatocellular carcinoma in Egyptian population by detection of serum miRNAs
Authors: Ghazy Sara Salama , Fyala Amira S. , Sultan Ahmed S. 
Published: July 2017

Abstract
The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and carries a poor survival rate. Prognosis, survival and management of patients at risk for developing HCC remain challenging in Egypt and worldwide. Furthermore, poor prognosis of patients with symptomatic (HCC) diagnosed clinically at advanced stages suggests an urgent need for new biomarkers detection that can be used for pre-clinical screening for early detection of premalignant lesions and tumors in high risk to hepatitis C infection.
In the present study we used novel formulated anticancer compound(s), combined with or without Sorafenib treatment to exert their antiproliferative effects by eliciting concomitant expression of known or novel biomarkers, including different serum miRNAs, which can be quantitatively analyzed for differences in the levels of metabolites and proteins in the blood and liver tissues of treated HCC xenografts and liver cirrhosis animal models. In addition, circulating miRNAs levels were measured as promising markers in 12 month interval-serum samples that were collected from normal, chronic hepatitis C virus infected patient cohorts at the pre-malignant or pre-clinical stages and liver cirrhotic patients that did not develop cancer. Different serum miRNAs, including miR-21, miR-142, let-7a, let-7b, miR-429 and miR-34a were detected in pre-clinical HCC patients and have the potential to screen for hepatitis C virus infected patients at high risk to develop HCC 12 months after miRNAs detection. Our data of detected serum miRNAs from animal models and patient samples can be used to confirm and correlate histological and histochemical results at various time points with serum or imaging biomarkers, which may have a great promise for the prediction and prevention of HCC in high risk Egyptian populations.
Citation Format: Sara Salama Ghazy, Amira S. Fyala, Ahmed S. Sultan. New predictive and preventive biomarkers for preclinical hepatocellular carcinoma in Egyptian population by detection of serum miRNAs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4440. doi:10.1158/1538-7445.AM2017-4440
Abstract 4443: SPARC overexpression alters microRNA expression profiles involved in tumor progression
Authors: Ahir Bhavesh K. , Lakka Sajani 
Published: July 2017

Abstract
Medulloblastoma is the most common of malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo and alters chemo sensitivity. MicroRNAs are a class of post-transcriptional gene regulators with critical functions in tumor progression. In addition, they also play role in regulation of vital genes that control mechanisms of chemo-resistance. Herein, we assessed microRNA (miRNA) profiling to identify the functional network and biological pathways altered in SPARC-overexpressed medulloblastoma cells. A total of 27 differentially expressed miRNAs were identified between the control and SPARC-overexpressed samples. Potential messenger RNA (mRNA) targets of the differentially expressed miRNA were identified using Ingenuity Pathway Analysis (IPA). Network-based functional analyses were performed on the available human protein interaction and miRNA-gene association data to highlight versatile miRNAs among the significantly deregulated miRNAs using the IPA, and the biological pathway analysis using the PANTHER web-based tool. We identified six miRNAs (miR-125b1*, miR-146a-5p, miR-181a-5p, miR-204-5p, miR-219-5p and miR-509-3p) which are differentially regulated with SPARC expression in medulloblastoma cells. Furthermore, pathway enrichment analysis outline that these six microRNAs mainly belong to biological processes related to cancer related signaling pathways. Collectively, these results suggest that a perturbed expression for these six miRNAs and their complex regulatory loops contribute to tumor suppressive effects in SPARC overexpressed medulloblastoma cells.
Citation Format: Bhavesh K. Ahir, Sajani Lakka. SPARC overexpression alters microRNA expression profiles involved in tumor progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4443. doi:10.1158/1538-7445.AM2017-4443
Abstract 4448: Elevated levels of circulating miR-34a-5p and miR-181c-3p during cancer initiation by aflatoxin B1
Authors: Livingstone Merricka C. , Roebuck Bill D. , Johnson Natalie M. , Kensler Thomas W. , Groopman John D. 
Published: July 2017

Abstract
MicroRNAs are small non-coding RNAs that affect gene expression. They are essential in normal physiological processes and have been implicated in carcinogenesis. Hepatocellular carcinoma (HCC) is the second leading cause of cancer death globally, with the risk factor aflatoxin (AFB1) estimated to play a causal role in up to 28% of all HCC cases. In this study, we analyzed circulating miRNAs in a quantitative rat cancer model that were previously found to be associated with AFB1 exposure in liver. Sera were examined from 3 groups of animals: rats dosed with AFB1 (200 µg) for 28 consecutive days receiving vehicle only or AFB1 plus the chemopreventive agent CDDO-Im (30 µmol), and controls (Johnson et al., CaPR, 2014). Small RNAs were isolated from these serum samples at the end of the dosing period and analyzed by RT-qPCR. Quantitative PCR results at the end of the carcinogenic 28-day dosing regimen revealed notable increased expression of miR-34a-5p and miR-181c-3p (13 fold and 170 fold, respectively) in the AFB1 treated samples compared to controls. This expression was reduced in animals that received complete protection from developing HCC by concurrent intervention with CDDO-Im. Additionally, miR-122-5p displayed increased expression (5 fold) and miR-541-5p was downregulated (0.08 fold) in the sera of AFB1-treated animals. Overall, the data suggest that serum expression of miR-34a-5p and 181c-3p during liver cancer initiation could give insight into increased risk of developing HCC. Supported by T32ES007141-31A1 and CA197222.
Citation Format: Merricka C. Livingstone, Bill D. Roebuck, Natalie M. Johnson, Thomas W. Kensler, John D. Groopman. Elevated levels of circulating miR-34a-5p and miR-181c-3p during cancer initiation by aflatoxin B1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4448. doi:10.1158/1538-7445.AM2017-4448