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Reverse-phase protein array

Wei Yang, Michael R Freeman, Natasha Kyprianou
Castration-resistant prostate cancer (CRPC) remains incurable despite the approval of several new treatments. Identification of new biomarkers and therapeutic targets to enable personalization of CRPC therapy, with the aim of maximizing therapeutic responses and minimizing toxicity in patients, is urgently needed. Prostate cancer progression and therapeutic resistance are frequently driven by aberrantly activated kinase signalling pathways that are amenable to pharmacological inhibition. Personalized phosphoproteomics, which enables the analysis of signalling networks in individual tumours, is a promising approach to advance personalized therapy by discovering biomarkers of pathway activity and clinically actionable targets...
May 11, 2018: Nature Reviews. Urology
Kengo Yanagita, Ryo Nagashio, Shi-Xu Jiang, Yuki Kuchitsu, Kazuo Hachimura, Masaaki Ichinoe, Satoshi Igawa, Eriko Fukuda, Naoki Goshima, Yukitoshi Satoh, Yoshiki Murakumo, Makoto Saegusa, Yuichi Sato
Our aim was to develop a serodiagnostic marker for lung cancer. Monoclonal antibodies were generated, and one antibody designated as KU-Lu-1, recognizing cytoskeleton-associated protein 4 (CKAP4), was studied further. To evaluate the utility of KU-Lu-1 antibody as a serodiagnostic marker for lung cancer, reverse-phase protein array analysis was performed with sera of 271 lung cancer patients and 100 healthy controls. CKAP4 was detected in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed...
May 2, 2018: American Journal of Pathology
Di Du, Wencai Ma, Melinda S Yates, Tao Chen, Karen H Lu, Yiling Lu, John N Weinstein, Russell R Broaddus, Gordon B Mills, Yuexin Liu
Background: The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to advanced-stage diseases. We sought to develop a biomarker model that predicts EEC surgical stage at the time of clinical diagnosis. Results: PSES was significantly correlated with surgical stage in the TCGA cohort ( P < 0.0001) and in the validation cohort ( P = 0.0003). Even among grade 1 or 2 tumors, PSES was significantly higher in advanced than in early stage tumors in both the TCGA ( P = 0...
April 13, 2018: Oncotarget
Mustafa A Barbhuiya, Manoj K Kashyap, Vinuth N Puttamallesh, Rekha Vijay Kumar, Xinyan Wu, Akhilesh Pandey, Harsha Gowda
The vast majority of esophageal cancers in China, India and Iran are esophageal squamous cell carcinomas (ESCC). A timely diagnosis provides surgical removal as the main therapeutic option for patients with ESCC. Currently, there are no targeted therapies available for ESCC. We carried out reverse phase protein array-based protein expression profiling of seven ESCC-derivedcell lines and a non-neoplastic esophageal epithelial cell line (Het-1A) to identify differentially expressed proteins in ESCC. SYK non-receptortyrosine kinase was overexpressed in six out of seven ESCC cell lines that were used in the study...
April 6, 2018: Oncotarget
Wei Zhao, Jun Li, Rehan Akbani, Han Liang, Gordon B Mills
An integrated analysis of DNA, RNA and protein, so called proteogenomic studies, has the potential to greatly increase our understanding of both normal physiology and disease development. However, such studies are challenged by a lack of a systematic approach to credential individual samples resulting in the introduction of noise into the system that limits the ability to identify important biological signals. Indeed, a recent proteogenomic CPTAC study identified 26% of samples as unsatisfactory, resulting in a marked increase in cost and loss of information content...
May 1, 2018: Molecular & Cellular Proteomics: MCP
Fieke W Hoff, Chenyue W Hu, Yihua Qiu, Andrew Ligeralde, Suk-Young Yoo, Eveline Sjm De Bont, Amina A Qutub, Terzah M Horton, Steven M Kornblau
Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, and the second leading cause of pediatric cancer death in developed countries. While the cure rate for newly-diagnosed ALL is excellent, the genetic heterogeneity and chemoresistance of leukemia cells at relapse makes individualized curative treatment plans difficult. We hypothesize that genetic events would coalesce into a finite number of protein signatures that could guide the design of individualized therapy. Custom Reverse Phase Protein Arrays were produced from pediatric ALL (n=73) and normal CD34+ (n=10) samples with 194 validated antibodies...
April 18, 2018: Molecular Cancer Research: MCR
Fieke W Hoff, Chenyue W Hu, Yihua Qiu, Andrew Ligeralde, Suk-Young Yoo, Hasan Mahmud, Eveline Sjm De Bont, Amina A Qutub, Terzah M Horton, Steven M Kornblau
Heterogeneity in the genetic landscape of pediatric acute myeloid leukemia (AML) makes personalized medicine challenging. As genetic events are mediated by the expression and function of proteins, recognition of recurrent protein patterns could enable classification of pediatric AML patients and could reveal crucial protein dependencies. This could help to rationally select combinations of therapeutic targets. To determine if protein expression levels could be clustered into functionally relevant groups, custom Reverse Phase Protein Arrays (RPPA) were performed on pediatric AML (n=95) and CD34+ normal bone marrow (n=10) clinical specimens using 194 validated antibodies...
April 18, 2018: Molecular Cancer Research: MCR
I-Hsuan Chen, Hillary Andaluz Aguilar, Juan Sebastian Paez Paez, Xiaofeng Wu, Li Pan, Michael K Wendt, Anton B Iliuk, Ying Zhang, W Andy Tao
Glycoproteins comprise more than half of current FDA-approved protein cancer markers but the development of new glycoproteins as disease biomarkers has been stagnant. Here we present a pipeline to develop glycoproteins from extracellular vesicles (EVs) through integrating quantitative glycoproteomics with a novel reverse phase glycoprotein array, and then apply it to identify novel biomarkers for breast cancer. EV glycoproteomics show promise in circumventing the problems plaguing current serum/plasma glycoproteomics and allowed us to identify hundreds of glycoproteins that have not been identified in blood...
April 9, 2018: Analytical Chemistry
Katherine A Hoadley, Christina Yau, Toshinori Hinoue, Denise M Wolf, Alexander J Lazar, Esther Drill, Ronglai Shen, Alison M Taylor, Andrew D Cherniack, Vésteinn Thorsson, Rehan Akbani, Reanne Bowlby, Christopher K Wong, Maciej Wiznerowicz, Francisco Sanchez-Vega, A Gordon Robertson, Barbara G Schneider, Michael S Lawrence, Houtan Noushmehr, Tathiane M Malta, Joshua M Stuart, Christopher C Benz, Peter W Laird
We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation...
April 5, 2018: Cell
Karineh Petrossian, Duc Nguyen, Chiao Lo, Noriko Kanaya, George Somlo, Yvonne Xiaoyong Cui, Chiun-Sheng Huang, Shiuan Chen
PURPOSE: HR+/HER2- aromatase inhibitor-resistant metastatic breast cancer can be treated with everolimus and a second AI until the cancer recurs. Targeting these everolimus-resistant patients with the latest standard of care, CDK4/6 inhibitors, has not been clearly addressed. Understanding the signaling transduction pathways, which everolimus resistance activates, will elucidate the mechanisms and offer treatment strategies of everolimus resistance. METHODS: To mimic the clinical setting, letrozole-resistant cells were used to generate an everolimus-resistant model (RAD-R)...
April 5, 2018: Breast Cancer Research and Treatment
Ren Wu, Ding Li, Qi Tang, Wanchun Wang, Guangrong Xie, Pengcheng Dou
Osteosarcoma (OS) is a typical bone cancer, and most frequently used cancer treatments for OS are limited due to severe drug-related toxicities. Wasp venoms contain functional components that may offer pharmaceutical components for the treatment of cancers. This study aimed to isolate and characterize a novel peptide (venom anti-cancer peptide 1, VACP1) derived from the wasp venom of Vespa ducalis SMITH. Toxins from Vespa ducalis crude venom were separated by gel filtration and purified by C18 reverse-phase HPLC...
2018: Biological & Pharmaceutical Bulletin
Josep Marí-Alexandre, Moisés Barceló-Molina, Elisa Belmonte-López, Javier García-Oms, Amparo Estellés, Aitana Braza-Boïls, Juan Gilabert-Estellés
OBJECTIVE: To define the microRNA (miRNA) profile and its relationship with cytokines content in peritoneal fluid (PF) from endometriosis patients. DESIGN: Case-control study. SETTING: University hospital, research institute. PATIENT(S): One hundred twenty-six women with endometriosis (EPF) and 45 control women (CPF). MAIN OUTCOMES MEASURE(S): MiRNA arrays were prepared from six EPF and six CPF...
March 28, 2018: Fertility and Sterility
Daniel Richard Gomez, Lauren Averett Byers, Monique Nilsson, Lixia Diao, Jing Wang, Lerong Li, Pan Tong, Mia Hofstad, Babita Saigal, Ignacio Wistuba, Neda Kalhor, Stephen Swisher, Youhong Fan, Waun Ki Hong, Milind Suraokar, Carmen Behrens, Cesar Moran, John Victor Heymach
While several molecular targets have been identified for adenocarcinoma (ACA) of the lung, similar drivers with squamous cell carcinoma (SCC) are sparse. We compared signaling pathways and potential therapeutic targets in lung SCC and ACA tumors using reverse phase proteomic arrays (RPPA) from two independent cohorts of resected early stage NSCLC patients: a testing set using an MDACC cohort (N=140) and a validation set using the Cancer Genome Atlas (TCGA) cohorts. We identified multiple potentially targetable proteins upregulated in SCC, including NRF2, Keap1, PARP, TrkB, and Chk2...
March 6, 2018: Oncotarget
Remi Adelaiye-Ogala, Nur P Damayanti, Ashley R Orillion, Sreevani Arisa, Sreenivasulu Chintala, Mark A Titus, Chinghai Kao, Roberto Pili
Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer. AR expression has also been reported in other solid tumors, including renal cell carcinoma (RCC), but its biological role here remains unclear. Through integrative analysis of a reverse phase protein array (RPPA), we discovered increased expression of AR in an RCC patient-derived xenograft model of acquired resistance to the receptor tyrosine kinase inhibitor (RTKi) sunitinib. AR expression was increased in RCC cell lines with either acquired or intrinsic sunitinib resistance in vitro...
March 23, 2018: Cancer Research
M A Gharaei, Y Xue, K Mustafa, S A Lie, I Fristad
BACKGROUND: Angiogenesis is of utmost importance for tissue regeneration and repair. Human dental pulp stromal cells (hDPSCs) possess angiogenic potential, as they secrete paracrine factors that may alter the host microenvironment. However, more insight into how hDPSCs guide endothelial cells (ECs) in a paracrine fashion is yet to be obtained. Therefore, the current study aimed to investigate the effect(s) of conditioned medium derived from hDPSCs (hDPSC-CM) on EC behavior in vitro. METHODS: hDPSCs were harvested from third molars scheduled for surgical removal under informed consent...
March 21, 2018: Stem Cell Research & Therapy
Michael Lehrer, Anindya Bhadra, Sathvik Aithala, Visweswaran Ravikumar, Youyun Zheng, Basak Dogan, Emerlinda Bonaccio, Elizabeth S Burnside, Elizabeth Morris, Elizabeth Sutton, Gary J Whitman, Jose Net, Kathy Brandt, Marie Ganott, Margarita Zuley, Arvind Rao
Background: Imaging features derived from MRI scans can be used for not only breast cancer detection and measuring disease extent, but can also determine gene expression and patient outcomes. The relationships between imaging features, gene/protein expression, and response to therapy hold potential to guide personalized medicine. We aim to characterize the relationship between radiologist-annotated tumor phenotypic features (based on MRI) and the underlying biological processes (based on proteomic profiling) in the tumor...
January 2018: Oncoscience
Steven M Kornblau, Peter P Ruvolo, Rui-Yu Wang, V Lokesh Battula, Elizabeth J Shpall, Vivian R Ruvolo, Teresa McQueen, YiHua Qui, Zhihong Zeng, Sherry Pierce, Rodrigo Jacamo, Suk-Young Yoo, Phuong M Le, Jeffrey Sun, Numsen Hail, Marina Konopleva, Michael Andreeff
Mesenchymal stromal cells (MSC) support acute myeloid leukemia (AML) cell survival in the bone marrow (BM) microenvironment. Protein expression profiles of AML-derived MSC are unknown. Reverse phase protein array analysis was performed to compare expression of 151 proteins from AML-MSC (n=106) with MSC from healthy donors (n=71). Protein expression differed significantly between the two groups with 19 proteins over-expressed in leukemia stromal cells and 9 over-expressed in normal stromal cells. Unbiased hierarchical clustering analysis of the samples using these 28 proteins revealed three protein constellations whose variation in expression defined four MSC protein expression signatures: Class 1, Class 2, Class 3, and Class 4...
May 2018: Haematologica
Jinho Lee, Gary K Geiss, Gokhan Demirkan, Christopher P Vellano, Brian Filanoski, Yiling Lu, Zhenlin Ju, Shuangxing Yu, Huifang Guo, Lisa Y Bogatzki, Warren E Carter, Rhonda K Meredith, Savitri Krishnamurthy, Zhiyong Ding, Joseph M Beechem, Gordon Mills
Molecular analysis of tumors forms the basis for personalized cancer medicine and increasingly guides patient selection for targeted therapy.  Future opportunities for personalized medicine are highlighted by the measurement of protein expression levels via immunohistochemistry, protein arrays, and other approaches; however, sample type, sample quantity, batch effects, and "time to result" are limiting factors for clinical application.  Here, we present a development pipeline for a novel multiplexed DNA-labeled antibody platform which digitally quantifies protein expression from lysate samples...
March 12, 2018: Molecular & Cellular Proteomics: MCP
Mehdi Moini
In the past few years, there has been a significant effort by the forensic science community to develop new scientific techniques for the analysis of forensic evidence. Forensic chemists have been spearheaded to develop information-rich confirmatory technologies and techniques and apply them to a broad array of forensic challenges. The purpose of these confirmatory techniques is to provide alternatives to presumptive techniques that rely on data such as color changes, pattern matching, or retention time alone, which are prone to more false positives...
March 12, 2018: Electrophoresis
Anneke D van Dijk, Chenyue W Hu, Eveline S J M de Bont, YiHua Qiu, Fieke W Hoff, Suk Young Yoo, Kevin R Coombes, Amina A Qutub, Steven M Kornblau
Posttranslational histone tail modifications are known to play a role in leukemogenesis and are therapeutic targets. A global analysis of the level and patterns of expression of multiple histone-modifying proteins (HMP) in acute myeloid leukemia (AML) and the effect of different patterns of expression on outcome and prognosis has not been investigated in AML patients. Here we analyzed 20 HMP by reverse phase protein array (RPPA) in a cohort of 205 newly diagnosed AML patients. Protein levels were correlated with patient and disease characteristics, including survival and mutational state...
April 2018: Proteomics
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