bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 866: Identification of novel early detection candidate protein biomarkers for ER+/PR+ invasive ductal breast carcinoma using pre-clinical plasma from the Women's Health Initiative Observational Study
Authors: Buas Matthew F. , Zhang Yuzheng , Rho Junghyun , Pepe Margaret , Lampe Paul , Li Christopher 
Published: May 2015

Abstract
Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for approximately 45% of all invasive breast cancers (BC) diagnosed in the United States each year. While mammography screening and adjuvant hormonal therapy have played key roles in reducing breast cancer mortality, an important challenge remains the development of clinically useful blood-based biomarkers for early detection. The objective of this study was to identify and initially validate novel candidate markers for ER+/PR+ ductal BC, using pre-clinical plasma samples collected up to 12.5 months before diagnosis from 121 cases, 121 matched controls, and 201 non-matched controls from the Women's Health Initiative Observational Study. These specimens were equally divided into training and testing sets and interrogated by a customized antibody array, which included over 3,000 antibodies targeting more than 2,000 proteins. In the training set, statistically significant differences in matched case versus control signals were observed for 374 (11.4 %) antibodies at P&lt;0.05, with 42 of these 374 candidates confirmed in the testing set (P&lt;0.05). Four markers remained significant in the pooled matched pairs sample set after Bonferroni correction for multiple comparisons (P&lt;0.05/3286=1.52x10-5). Areas under the curve for the full list of candidates ranged from 0.55 to 0.66, when assessed in an expanded sample including non-matched controls. With specificity set at 95%, sensitivity ranged from 4 to 19%, with six candidates having a sensitivity of ≥15% at 95% specificity and ≥20% at 90% specificity. The majority of these putative markers did not overlap with those identified in a parallel analysis of triple-negative BC from the same cohort population, suggesting the potential for BC sub-type specificity at the level of the pre-clinical plasma proteome. Additional studies are needed to validate these findings in larger sample sets and further explore their biologic implications in relation to ER+/PR+ BC etiology.
Citation Format: Matthew F. Buas, Yuzheng Zhang, Junghyun Rho, Margaret Pepe, Paul Lampe, Christopher Li. Identification of novel early detection candidate protein biomarkers for ER+/PR+ invasive ductal breast carcinoma using pre-clinical plasma from the Women's Health Initiative Observational 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 866. doi:10.1158/1538-7445.AM2014-866
Abstract 868: Characterization of LASEP3 as a serological and prognostic biomarker and a therapeutic target for lung cancer
Authors: Takano Atsushi , Nakamura Yusuke , Daigo Yataro 
Published: May 2015

Abstract
This study aims to identify novel biomarkers or therapeutic targets for lung cancers. We used cDNA microarrays for screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers. During this process, we identified a secreted protein, LASEP3 (lung cancer-associated serum protein 3) as a candidate. Immunohistochemical staining of LASEP3 showed that LASEP3 expression was observed in 198 (54.8%) of 361 NSCLCs (non-small cell lung cancer) that had undergone curative surgery. High level of LASEP3 expression was associated with poor prognosis for NSCLC patients. (P=0.0183 by log-rank test). Serum LASEP3 levels were higher in NSCLC patients than in healthy volunteers. The proportion of serum LASEP3-positive cases was 160 (61.8%) of 259 NSCLCs (49.4% for stage I-II, 67.4% for stage III-IV), while 6 (5.5%) of 109 healthy volunteers were falsely diagnosed. Moreover serum LASEP3 levels were significantly higher in breast and colon cancer patients than in healthy volunteers. LASEP3 protein was overexpressed in breast and colon cancer tissues. Furthermore, reduction of LASEP3 by siRNA suppressed lung cancer cell proliferation and invasion. Flow cytometric analysis of these tumor cells transfected with siRNAs for LASEP3 revealed a significant increase of the cells at the G1 phase. Furthermore, subsequent microarray analysis of these cancer cells identified several candidate downstream genes of LASEP3 that relate to cell growth signals. These data suggest that LASEP3 is a possible diagnostic and prognostic biomarker and therapeutic target for lung and various types of solid cancer.
Citation Format: Atsushi Takano, Yusuke Nakamura, Yataro Daigo. Characterization of LASEP3 as a serological and prognostic biomarker and a therapeutic target for lung 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 868. doi:10.1158/1538-7445.AM2014-868
Abstract 872: APE1/Ref-1 as a serological biomarker for the detection of bladder cancer
Authors: Choi Sunga , Shin Ju Hyun , Lee Yu Ran , Park Myoung Soo , Yim Chang Nam , Na Young Gil , Lim Jae Sung , Jeon Byeong Hwa 
Published: May 2015

Abstract
Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a DNA repair enzyme whose expression is increased in several forms of cancerous cells. We investigated whether serum APE1/Ref-1 is elevated in patients with bladder cancer. Tumor tissue and serum from patients with bladder cancer who had not received chemotherapy or radiotherapy (n=51) and non-tumor healthy controls (n=55) was used. In immunohistochemistry, and immunoblot analysis, the APE1/Ref-1 protein level of bladder tissues was increased in patients with bladder cancer. The serum APE1/Ref-1 levels were significantly elevated in bladder cancer patients than in those of non-tumor healthy controls and its levels were correlated with tumor staging and grading. The ROC curve of APE1/Ref-1 showed an excellent area under the ROC curve of 0.824. In this study, the optimal combination of sensitivity and specificity were determined as 93% and 59% for a cut-off value of serum APE1/Ref-1 of 2.83 ng/100 μl, respectively. The serum APE1/Ref-1 levels are increased in patients with bladder cancer with recurrence. These data indicate serum APE1/Ref-1 may help to identify patients with bladder cancer and it can be used as a serological marker of bladder cancer.
Citation Format: Sunga Choi, Ju Hyun Shin, Yu Ran Lee, Myoung Soo Park, Chang Nam Yim, Young Gil Na, Jae Sung Lim, Byeong Hwa Jeon. APE1/Ref-1 as a serological biomarker for the detection of bladder 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 872. doi:10.1158/1538-7445.AM2014-872
Abstract 878: Identification and characterization of tumor-associated antigens as biomarkers in human prostate cancer
Authors: Li Jitian , Dai Liping , Casiano Carlos A. , Zhang Jianying 
Published: May 2015

Abstract
Autoantibodies against intracellular antigens are commonly found in a number of systemic autoimmune diseases. Their utility in providing insights into molecular and cellular biology and in the differential diagnosis of autoimmune diseases is well documented. Autoimmune phenomena manifested as antibodies to cellular components have been described in many types of cancer. Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the second leading cause of male cancer deaths in the United States. PCa also presents the greatest racial disparity in this country, with an incidence and mortality in African-American men that is 3 times higher than in White and Latino men. Reducing these disparities would require a multi-faceted approach that includes developing more effective screening method for the early detection of PCa. The objective of this study is to analyze the frequency and specificity of autoantibodies in PCa patients, and further to identify and characterize the targeted tumor-associated antigens. In this study, 34 sera from PCa patients, and 30 sera from normal human individuals were examined for autoantibodies using indirect immunofluorescence (IIF) assay and western blotting. Autoantibodies were detected in 18 of 34 (52.9%) PCa sera by IIF, which was significantly higher than that in normal human sera. Of the interest is that of 34 PCa sera, 9 (26.5%) sera were identified by western blotting analysis containing antibodies against an unknown 70kDa cellular protein and 23.5% PCa patients showed antibody to 45 kDa protein. No reactivity with 70KDa and 45kDa proteins was detected in 30 normal human sera. In the further study, these cellular proteins targeted by serum antibodies in PCa were identified by using two-dimensional gel electrophoresis (2DE) and liquid chromatography-tandem-mass spectrometry (LC-MS/MS). This preliminary data supports that autoimmune responses to certain cellular proteins maybe a by-product in the transformation to PCa, and further studies of novel targeted proteins in PCa may provide insights into how these proteins might be involved in malignancy.
Citation Format: Jitian Li, Liping Dai, Carlos A. Casiano, Jianying Zhang. Identification and characterization of tumor-associated antigens as biomarkers in human prostate 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 878. doi:10.1158/1538-7445.AM2014-878
Abstract 879: New serum biomarkers for prostate cancer diagnosis
Authors: Chadha Kailash C. , Miller Austin , Nair Bindukumar B. , Schwartz Stanley A. , Trump Donald L. , Underwood Willie 
Published: May 2015

Abstract
Prostate-specific antigen (PSA) is currently used as a biomarker for the early diagnosis and management of prostate cancer (CaP). However, PSA generally lacks the sensitivity and specificity desired of an effective diagnostic biomarker. The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign vs. malignant prostate disease and/or localized CaP vs. metastatic CaP.
Concurrent measurements of circulating IL-8, TNF-alpha (TNF-α) and sTNFR1 were obtained from four groups of men: (1) controls (2) men with elevated PSA with a negative prostate biopsy (eIPSA_negBx) (3) men with clinically localized CaP and (4) men with castration resistant CaP (CRPC). TNF-α (AUC=0.93) and sTNFR1 (AUC=0.97) were strong predictors of elPSA_negBx vs CaP). The best predictor of elPSA_negBx vs prostate cancer was sTNFR1 and IL8 combined (AUC=0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC=0.992) and PSA (AUC=0.963) levels. Conclusions: The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in larger cohort consisting of Caucasians and African Americans is warranted.
Citation Format: Kailash C. Chadha, Austin Miller, Bindukumar B. Nair, Stanley A. Schwartz, Donald L. Trump, Willie Underwood. New serum biomarkers for prostate cancer diagnosis. [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 879. doi:10.1158/1538-7445.AM2014-879
Abstract 882: Non-invasive diagnostic testing for lung cancer in a prospective cohort
Authors: Tobi Martin , Sayre Joe , Rambus MaryAnn , Antaki Fadi , Schwartz Ann , Lawson Michael J. 
Published: May 2015

Abstract
Monoclonal antibody Adnab-9 recognizes the p87 antigen, a constituent of putatively activated pulmonary type 2 pneumocytes. p87 shed into sputum and swallowed may be a potential tumor marker detectable by the Adnab-9 stool test. We describe prospectively collected stool and colonic effluent ELISA results in a cohort of urban patients enrolled in a colorectal cancer screening study. Methods: Prospectively, 1,132 American patients in Metropolitan Detroit submitted stool in a CRC prospective screening study from 1996 to 2013. Eleven patients free of any significant colorectal neoplasia or other cancer, but who had died from non-cancer-related causes, served as controls. Patients and controls were approximately 50-80 years old and the male to female ratios were similar (30:1 and 10:1). Sixty-seven percent of patients and 45 % of controls were African American. Results: 64 patients of 1,132 contracted lung cancer during the 17 year period of follow-up (5.7%). Of these 64 patients, 34 (52%) had stool or effluent Adnab-9 binding tests on retrospective review. We found that over half the patients ultimately diagnosed with lung cancer had either stool/effluent ELISA or Western blot positivity for Adnab-9 compared to only 1 of 11 controls (OR = 11.3, CI 1.3-97.9, p=0.014). The median time from stool submission to diagnosis of lung cancer was 4.4 (0.7-10.3) years. Lung Cancer Tumor types were adenocarcinoma in 23%; squamous in 33%; other in 20%; large cell cancer in 9%; small cell cancer in 8%; and unknown in 7%. At the last time of follow-up, 70% of patients subsequently diagnosed with lung cancer were deceased. Median survival time was 2.1 years from the time of clinical diagnosis. Conclusion: Adnab-9 sensitivity in this cohort was 52% with specificity of 90.9% for lung cancer and could lead to the diagnosis of lung cancer 4.4 years before clinical diagnosis was made. This supports the notion that accessible, early non-invasive testing combined with effective follow-up studies may lead to earlier diagnosis and treatment of lung cancer, the World's most frequent cancer.
Citation Format: Martin Tobi, Joe Sayre, MaryAnn Rambus, Fadi Antaki, Ann Schwartz, Michael J. Lawson. Non-invasive diagnostic testing for lung cancer in a prospective cohort. [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 882. doi:10.1158/1538-7445.AM2014-882
Abstract 887: Proteome scale identification of autoantibody biomarkers in colorectal cancer
Authors: Demirkan Gokhan , Soderberg Leah , Wallstrom Garrick , Szeto Emily , Barker Kristi , Wang Jie , LaBaer Joshua , Lindor Noralane M. , Qiu Ji 
Published: May 2015

Abstract
It is widely appreciated that early detection is the key to making inroads in the fight against cancers. Despite the availability of endoscopic screening, compliance is poor. The diagnosis of CRC is often made in advanced stages, and the consequence is a dismal 50% five year survival across all CRC. There is urgent need for biomarkers with performance that can meet the need of early diagnosis. Like most cancers, colorectal cancers (CRCs) express tumor antigens that can induce humoral immune response. The identification of the autoantibodies against tumor antigens may facilitate early diagnosis of CRC. The goal for this pilot project was to demonstrate the feasibility of discovering autoantibody biomarkers for colorectal cancer using Nucleic Acid Programmable Protein Arrays (NAPPA). Autoantibodies in serum samples collected from 40 patients with DNA mismatch repair proficient colorectal cancer who had died of their cancer within 18 months of their blood draw and from 40 age-gender matched healthy controls were profiled on NAPPA arrays with randomly selected 2000 human protein. The fact that p53, a tumor antigen that has been previously reported to be related to various cancers including CRC, was one of the top candidates based on the statistical analysis demonstrates the validity of our discovery platform. Besides p53, thirty-one candidate antigens were identified to have sensitivity greater than or equal to 25% at 95% specificity and fifty-one candidate antigens had an area under the ROC curve (AUC) equal to or greater than 0.6. Validation of the combined 83 unique genes selected based on these two different data analysis methods in an independent sample set in a blind fashion is on-going. This pilot study using late stage cancer samples demonstrates the feasibility and power of an immunoproteomics study using protein arrays. This approach may rapidly lead to identification of markers that could have relevance in monitoring disease progression as well as in early cancer detection.
Citation Format: Gokhan Demirkan, Leah Soderberg, Garrick Wallstrom, Emily Szeto, Kristi Barker, Jie Wang, Joshua LaBaer, Noralane M. Lindor, Ji Qiu. Proteome scale identification of autoantibody biomarkers in colorectal 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 887. doi:10.1158/1538-7445.AM2014-887
Abstract 888: Development of a urine DNA based marker panel for early detection of liver cancer
Authors: Chen Sitong , Jain Surbhi , Lin Selena , Su Ying-Hsiu , Song Wei 
Published: May 2015

Abstract
Hepatocellular carcinoma (HCC) or liver cancer is an aggressive disease and one of the fastest growing cancers in incidence in the United States. The 5 year survival rate drops dramatically from a poor 26% in early stages to a mere 2% in later stages of the disease. Currently, the only available biomarker for early detection is serum alpha-fetoprotein which can identify only 40-60% of cases. We aim to improve the poor disease prognosis by developing a screening test capable of detecting liver cancer in its earlier stages. Since cancer is a disease of the genome and epigenome, if we can detect these underlying genetic mutations and epigenetic modifications in the periphery, we should be able to effectively detect cancer early. We have previously shown that urine contains fragmented, cell-free, cancer related DNA, both mutated and methylated, derived from the circulation of cancer patients. We have also demonstrated that the concentration of tumor-derived DNA in plasma and in urine is similar in patients with tumors. Hence, we propose the use of a panel of HCC-associated genetic and epigenetic methylation DNA biomarkers to develop a sensitive, noninvasive urine screening test for HCC. In order to detect these markers in the circulation derived urine DNA, we developed short amplicon (∼50 bp) PCR based assays targeting HCC-associated mutations in TP53, CTNNB1, hTERT genes and HCC associated methylation in GSTP1, RASSF1A and CDKN2A. Urine DNA isolated from hepatitis, cirrhosis and HCC patients were tested in each of the assays and analyzed. Panel performance parameters such as sensitivity, specificity and area under the receiver operating curve were calculated for individual markers and then as a group in order to evaluate their ability to distinguish HCC patients from hepatitis and cirrhosis subjects. The potential of this urine test in the early detection of HCC is discussed.
Citation Format: Sitong Chen, Surbhi Jain, Selena Lin, Ying-Hsiu Su, Wei Song. Development of a urine DNA based marker panel for early detection of liver 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 888. doi:10.1158/1538-7445.AM2014-888
Abstract 892: Potential of urinary MMP-9/NGAL complex as a novel biomarker for the early detection of gastric cancer
Authors: Shimjura Takaya , Dagher Adelle , Ebi Masahide , Yamada Tamaki , Yamada Tomonori , Joh Takashi , Moses Marsha A. 
Published: May 2015

Abstract
The early diagnosis of gastric cancer (GC) provides the opportunity for curative endoscopic resection. However, although endoscopy is a standard diagnostic method for this disease, comprehensive screening endoscopy would be invasive, expensive and could result in significant complications. To date, there is a significant lack of useful GC biomarkers. In fact, serum tumor markers such as CEA and CA19-9 have not been recommended as GC diagnostics due to their low sensitivity and specificity. With the goal of discovering non-invasive biomarkers for the early diagnosis of GC, we have conducted a pilot case-control study utilizing urine samples from individuals with gastric cancer vs. healthy control samples. A cohort of 70 patients composed of 35 patients with gastric cancer and 35 age- and sex-matched healthy controls was analyzed. Baseline clinical characteristics were tightly controlled and no significant differences were noted. Since changes in the microvasculature have been described in the very early stages of GC, we conducted an angiogenesis protein array analysis to identify potential candidate biomarkers. Three proteins, IL-8, PECAM-1, MMP-9, were found to be elevated in the urine of GC patients compared to controls by this method. In confirming the elevated levels of urinary MMP-9 by gelatin zymography, we determined that MMP-9/NGAL complex was also significantly elevated in the GC urines compared to control samples. We therefore tested all samples for the presence of IL-8, PECAM-1, MMP-9 and MMP-9/NGAL complex using monospecific ELISAs. We were able to confirm that urinary levels of MMP-9/NGAL complex were significantly higher in the GC group compared to the healthy control group (Median, 85 pg/ml (IQR, 43-224) vs. 0 pg/ml (IQR, 0-213), respectively, P=0.020). Urinary MMP-9/NGAL complex could distinguish between healthy control samples and GC samples with an area under the curve of 0.657(95%CI, 0.527-0.789) in a receiver operating characteristics analysis. A cut-off value of urinary MMP-9/NGAL complex was established and the statistical performance characteristics of this urinary biomarker were also determined. In summary, urinary MMP-9/NGAL complex emerged as a significant non-invasive biomarker for gastric cancer including early stage disease. Ongoing studies are focused on the large scale validation of these findings.
Citation Format: Takaya Shimjura, Adelle Dagher, Masahide Ebi, Tamaki Yamada, Tomonori Yamada, Takashi Joh, Marsha A. Moses. Potential of urinary MMP-9/NGAL complex as a novel biomarker for the early detection of gastric 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 892. doi:10.1158/1538-7445.AM2014-892