bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4276: Target enrichment to enable RNA-sequencing on FFPE samples: Application to a patient selection biomarkers in colorectal cancer
Authors: Rogers-Grazado Maximilian , Theilhaber Joachim , Pollard Jack , Protopopov Alexei 
Published: September 2020

Abstract
In proof of concept clinical studies, selecting for patients that are the most likely to respond to a given therapy will increase the chance of demonstrating clinical benefit for a new investigational agent.
Archived Formalin-Fixed, Paraffin-Embedded (FFPE) tissue taken at the time of first biopsy and cancer diagnosis are a ready source of material for such patient selection assays; however if the selection assay is RNA-based sequencing based assay, FFPE tumor tissues are typically refractory to standard methods. Here we describe Target Enrichment, an RNA-sequencing technique that enabled analysis of FFPE tumor tissue. The Target Enrichment technique provides the necessary, high quality gene expression data required for identifying the mesenchymal subtype of CRC. In this experiment, RNA was extracted from a set of 192 histologically characterized, archived colorectal cancer (CRC) FFPE tumor tissues with sufficient representation of all Consensus Molecular Subtypes of CRC.
A major issue with FFPE tissue is that nucleic acids are not well preserved in the fixation process. The RNA extraction method was carefully optimized in advance toward improving yield and integrity of the total RNA. In order to accommodate the low FFPE RNA integrity, we used Target Enrichment, a technique derived from whole-exome sequencing that isolates and amplifies library fragments corresponding to only the transcribed regions of interest. After testing several protocols, we established a Target Enrichment technique to remove low-quality library fragments that would otherwise interfere and impair sequencing quality.
This method allowed us to generate high-quality sequencing data for samples that proved challenging using traditional RNA-seq methods. Fresh-frozen tissue samples were used as a benchmark and our Target Enrichment technique showed comparable performance across multiple sequencing quality metrics including mapping rate, expression profiling efficiency, number of genes detected, also the pass rate. Furthermore, data generated using our Target Enrichment technique aligned with the known frequencies of the Consensus Molecular Subtypes of CRC.
Overall, our Target Enrichment technique provides a protocol for generating high quality RNA-seq libraries from highly degraded FFPE RNA.
Citation Format: Maximilian Rogers-Grazado, Joachim Theilhaber, Jack Pollard, Alexei Protopopov. Target enrichment to enable RNA-sequencing on FFPE samples: Application to a patient selection biomarkers in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4276.
Abstract 43: Fully integrated single instrument imaging-based digital PCR platform
Authors: Lin Robert , Zayac Andrew , Gallagher Steve , Jiang Lingxia , Linn Felicia , Hung Paul 
Published: September 2020

Abstract
Digital PCR (dPCR) has gained popularity in recent years for cancer research such as rare mutation detection, minimal residual disease, treatment selection, and recurrence monitoring. However, currently available technologies suffer from several limitations such as tedious workflow, long time-to-result, poor multiplexity, and inconsistent reagent digitization that severely hindered its broad adoption. We have designed and manufactured a dPCR platform that is capable of consistent sample digitization, thermal cycling and simultaneous interrogation of 20,000 partitions with walk-away workflow. The instrument integrates a loading and digitization manifold, a thermal cycler and an imaging engine with 5 optical channels into a single benchtop box. The Microfluidic Array Partitioning (MAP) consumable is a micro-injection molded, automation-ready plate that contains 16 individual units that can be loaded simultaneously. Each unit partitions an individual sample into 20,000 fluidically isolated partitions while utilizing &gt;90% of inputted sample. We utilized an oncology standard assay, confocal microscopy, and real-time imaging to validate the dynamic range, sample utilization, and digitization consistency of the platform, respectively. Using the European Breast Cancer Standards ERM-AD623 we quantified replicates that were serially diluted from 1 × 105cp/μL down to 10cp/μL. We demonstrated that the dPCR platform can consistently quantify targets over 5-orders-of-magnitude of concentration with high consistency in both quantification and partition numbers. With confocal microscopy, the reagent inside the partitions are visualized to characterize sample utilization. Using conventional qPCR calibration dye ROX and real-time imaging, we show that over 99% of the partitions can be consistently analyzed for high quantification confidence. With the combination of ease-of-use, fast time-to-result and consistent performance, we believe this novel dPCR platform provides unparalleled usability and capability and will allow dPCR to fulfill its promise to impact cancer patient care.
Citation Format: Robert Lin, Andrew Zayac, Steve Gallagher, Lingxia Jiang, Felicia Linn, Paul Hung. Fully integrated single instrument imaging-based digital PCR platform [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 43.
Abstract 4306: Retrospective analysis of docetaxel in combination with ramucirumab for previously treated non-small cell lung cancer patients
Authors: Kitadai Rui , Yoshimura Akihiro , Yamada Tadaaki , Okuma Yusuke , Takeda Takayuki , Kanematsu Takanori , Uchino Junji , Nishioka Yasuhiko , Takayama Koichi 
Published: September 2020

Abstract
BACKGROUND: Current clinical trials demonstrated that combination regimens comprising chemotherapy and immunotherapy lead to better patient outcomes compared to chemotherapy alone as the first line of treatment for non-small cell lung cancer (NSCLC). In addition, the combination therapy of docetaxel (Doc) and ramucirumab (Ram) was considered one of the standard treatments for advanced or relapsed NSCLC patients. However, little is known about the therapeutic responders of this combination therapy among previously treated NSCLC patients. In the present study, we aimed to identify predictive factors for therapeutic response, including programmed death-ligand 1 (PD-L1) expression in tumors, for Doc treatment in combination with Ram.
METHODS: We retrospectively analyzed a total of 135 advanced or relapsed NSCLC patients who were refractory to platinum-based chemotherapy at eleven institutions in Japan between July 2016 and November 2018.
RESULTS: Our observations showed that PD-L1 expression in tumors is not associated with the efficacy of combined therapy of Doc and Ram in previously treated NSCLC patients. Analysis of the patient clinical profiles indicated that prior treatment with immune checkpoint inhibitors (ICIs) is a reliable predictor for the good progression-free survival (PFS) to this combination therapy (P=0.041).
CONCLUSIONS: Our retrospective study indicated that combination regimens comprising chemotherapy and ICIs followed by Doc and Ram could be an optimal therapeutic option for NSCLC patients regardless of the PD-L1 status of tumors. Further investigations are required to strengthen clinical evidence demonstrating the effectiveness of the combination therapy of Doc plus Ram in previously treated NSCLC patients.
Citation Format: Rui Kitadai, Akihiro Yoshimura, Tadaaki Yamada, Yusuke Okuma, Takayuki Takeda, Takanori Kanematsu, Junji Uchino, Yasuhiko Nishioka, Koichi Takayama. Retrospective analysis of docetaxel in combination with ramucirumab for previously treated non-small cell lung cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4306.
Abstract 4311: PPIB expression associates with tumor progression and unfavorable disease-free survival of non-small cell lung cancer
Authors: Kim Jeongwon , Chung Joon-Yong , Hewitt Stephen M. , Hwang Ilseon , Song Joon Seon , Choi Chang-Min , Cho Eunho , Song Kwon-Ho , Kim Tae Woo , Ylaya Kris 
Published: September 2020

Abstract
Background: PPIB (Peptidylprolyl isomerase B) is involved in cellular transcriptional regulation, immune response, chemotaxis, and proliferation. Recent studies have shown that PPIB is linked to tumor progression and chemoresistance. The role of PPIB in non-small cell lung cancer (NSCLC) has not been explored. We aimed to investigate the significance of PPIB in NSCLC and its mechanism of action.
Methods: The role of PPIB was assessed in 5 human NSCLC cell lines. PPIB expression was examined using RNA in situ hybridization (RNA-ISH) on tissue microarrays consisting of 544 NSCLC cases and Ki-67 expression was evaluated by immunohistochemical assays (IHC). RNA-ISH and IHC scores were evaluated by digital image analysis and used to compare patients' prognostic outcomes.
Results: PPIB overexpression promoted proliferation, colony formation and migration of NSCLC tumor cells. We also confirmed the oncogenic properties of PPIB expression in PPIB transfected human bronchogenic epithelial cells. In NSCLC tumor samples, high PPIB expression correlated with lymph node metastasis and recurrence (p = 0.018 and 0.026, respectively), while Ki-67 overexpression correlated with advanced tumor stage (p &lt; 0.001). Patients with high PPIB expression assessed by RNA-ISH (PPIBhigh), exhibited significantly shorter disease-free survival (DFS) time than those who were PPIBlow [HR (95% CI) = 1.53 (1.11-2.10), p = 0.008]. Multivariate analysis revealed that combined Ki-67high/PPIBhigh expression was an independent predictor of shorter DFS [HR (95% CI) = 1.71 (1.26-2.31), p &lt; 0.001].
Conclusions: These findings suggest that PPIB plays a role in NSCLC tumor growth and is associated with unfavorable disease-free survival. PPIB may have value as a prognostic marker and a potential target molecule for NSCLC treatment.
Citation Format: Jeongwon Kim, Joon-Yong Chung, Stephen M. Hewitt, Ilseon Hwang, Joon Seon Song, Chang-Min Choi, Eunho Cho, Kwon-Ho Song, Tae Woo Kim, Kris Ylaya. PPIB expression associates with tumor progression and unfavorable disease-free survival of non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4311.
Abstract 4316: Frequent microsatellite instability in Chinese solid tumor patients
Authors: Wang Huilin , Zhu Jiang , Liang Guanbiao , Wang Yongyong , Guo Jianji , Zheng Min , Fu Qin , Shi Weiwei 
Published: September 2020

Abstract
Background Microsatellite instability (MSI) has important clinical implications related to therapeutic options and prognostic assessment. Few studies have been done on the frequency of MSI in cancers and the correlation between microsatellite status and clinicopathological features in Chinese solid tumor patients.
Methods A total of 10149 Chinese solid tumor patients were collected for genome testing using a targeted next-generation sequencing (NGS) panel (OrigiMed, Shanghai). Microsatellite status and other clinicopathological features were examined. Fisher's exact test was used for statistical analysis.
Results MSI-high (MSI-H) was observed in 188 solid tumors (1.8%). Cancer subtypes with significantly higher MSI frequencies included colorectal adenocarcinoma (8.4%), gastric adenocarcinoma (6.9%) and intrahepatic cholangiocarcinoma (2.7%). No statistical significant difference was found in the proportion of MSI in women and men (1.9 % vs 1.7%, respectively). The proportion MSI tumors was higher in older patients (1.3% at 60-69 years, 2.8% at 70-79 years,P&lt;0.0001) and younger patients (1.4% at 50-59 years, 3.0% at 40-49 years, P&lt;0.0001). Compared with microsatellite stable (MSS) carcinomas, MSI was significantly correlated with the oldest and youngest age ranges that were tested, tumors found in the stomach and intestine, and in colorectal adenocarcinoma and gastric adenocarcinoma subtypes. In addition, 123 of the 188 samples (65.4%) harbored at least one MMR gene mutations predicted as loss of functions, including nonsense mutations or truncations in MSH2, MSH6 or MLH1. 2.3% (217/9354) MMR gene mutation was detected in MSS samples (p&lt;0.0001).
Conclusions This study revealed MSI-H in approximately 1.8% of Chinese solid tumor patients and a significant association between MSI-H and MMR gene mutations. These results suggest that there are specific tumor types and clinicopathological features associated with a higher frequency of MSI, indicating a bias during tumorigenesis. Also, these results may potentially contribute to more effective treatment options and a better prognostic assessment for solid tumor patients.
Citation Format: Huilin Wang, Jiang Zhu, Guanbiao Liang, Yongyong Wang, Jianji Guo, Min Zheng, Qin Fu, Weiwei Shi. Frequent microsatellite instability in Chinese solid tumor patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4316.
Abstract 4346: Training Minority Community Leaders on Prostate Cancer. Effect of an Educational Strategy in Los Angeles, CA & Tallahassee, FL
Authors: Aristizabal Carolina 
Published: September 2020

Abstract
Background: Certain groups are disproportionately impacted by prostate cancer (PCa) compared to other racial/ethnic groups such as Blacks. While the burden of PCa in Hispanics is low, there is limited understanding of the disparities in subpopulations of Hispanics. We developed and culturally adapted, and updated all the scientific data, translated, implemented and evaluated a Prostate Cancer Advocacy Training (PCAT) for Hispanic populations.
Methods: Culturally and language specific content on PCa cause, risk factors, epidemiology, detection, diagnosis and treatment was delivered through a workshop and simultaneously broadcasted in Spanish in Los Angeles County (n=29) and in English in Tallahassee, Florida (n=9). Pre- and post-test surveys assessed impact.
Results: The following pre vs. post differences were statistically significant (p &lt; 0.05), in knowledge (5.0±1.6 vs 6.3±1.1) and advocacy intentions (3.9±0.9 vs 4.3±0.8). On correctly identifying warning signs for PCa (50% vs 87%), intent to inform and educate patients, family, and friends about PCa within the next three months, (69% vs 95%), to ensure that high quality research is sensitive to the priorities of patients (63% vs 84%), to help increase patient recruitment, compliance and retention for clinical trials within the next month (62% vs 84%), intent to engage in PCa patient education within the next three months, (67% vs 92%); and in engaging in PCa community outreach within the next three months, (67% vs 94%) There were no significant differences due to race/ethnicity.
Conclusion: The PCAT led to increased knowledge, awareness, and intention to engage patients and community health workers in advocacy and engagement regarding PCa in the next three months. Results suggest that delivering culturally and language specific educational information increases engagement of Hispanic and African American patient/community advocates. This has implications for reducing cancer health disparities.
Citation Format: Carolina Aristizabal. Training Minority Community Leaders on Prostate Cancer. Effect of an Educational Strategy in Los Angeles, CA & Tallahassee, FL [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4346.
Abstract 4353: The Fibrolamellar Registry: A patient-based medical registry can address medical care
Authors: Newcomb Julie Latone , Lett Siobhan , Migler Rachael D. , Simon Elana P. , Simon Sanford M. 
Published: September 2020

Abstract
Advances in genomics and proteomics have enabled more precise characterizations of tumors with the consequence that many cancers are being segregated into smaller categories. With this larger number of categories, more cancers are being categorized as rare. The downside to such categorizations is that the reduced numbers of patients in each category makes it difficult to gather enough information about each cancer. We are a group of patients and caregivers who have joined together to form a repository for patient-shared data and reports in an IRB-approved, non-profit medical registry for the rare and usually lethal childhood liver cancer fibrolamellar hepatocellular carcinoma (FLC). Since the Fibrolamellar Registry is patient-run and patient-owned, we have the trust of the patient community that the records will not be sold for profit. This has enabled us, in our first 3 years, to gather detailed medical records, scans and tests from over 170 patients. With input from scientists and clinicians who study FLC, we have written 600 questions of specific interest to this disease. Most of our patients have also opted to allow these medical records to be shared with a tissue FLC repository that already has samples from 110 patients. Many of patients with FLC get hyperammonenic encephalopathy. These patients do not respond to lactulose and, unfortunately, often enter a coma and die from the condition. From evaluation of our medical records the results indicate that patients do not have hyperammonenic encephalopathy as a result of liver failure. Instead, it is the result of an alteration of the expression of ornithine transcarbamylase, as a consequence of the expression of oncokinase that drives fibrolamellar. These alterations of ornithine transcarbamylase shift the urea acid cycle, resulting in the buildup of ammonia. This suggests that hyperammonemic encephalopathy should be treated with agents that modulate the urea acid cycle rather than lactulose. These results are an example of the power of a patient-run medical registry.
Citation Format: Julie Latone Newcomb, Siobhan Lett, Rachael D. Migler, Elana P. Simon, Sanford M. Simon. The Fibrolamellar Registry: A patient-based medical registry can address medical care [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4353.
Abstract 4426: Redox regulation of tumor cell heterogeneity in the PyMT mammary tumor model revealed by single cell RNA sequencing
Authors: Ren Zuen , Dharmaratne Malindrie , Kulkarni Ameya , Fard Atefeh Taherian , Mar Jessica , Galbo Phillip M. , Liu Yang , Zheng Deyou , Liang Huizhi , Benard Outhiriaradjou , Suyama Kimita , Prystowsky Michael B. , Norton Larry , Hazan Rachel B. 
Published: September 2020

Abstract
Tumor heterogeneity is known to drive breast cancer progression and metastasis. Current therapies target mostly inter-tumor heterogeneity (different patients) without taking into consideration intratumor heterogeneity (individual tumor). Hypoxia is a hallmark of aggressive tumors that is known to select for intratumor cells that are prone for metastasis. Here we show that knockdown of a ROS scavenging enzyme, Glutathione Peroxidase 2, in the PyMT mammary tumor model results in highly hypoxic and metastatic tumors. Single cell RNA-seq on both GPx2 knockdown and control tumors revealed a high degree of intratumor heterogeneity resulting in several clusters that were either of luminal/epithelial or basal-like/mesenchymal type shared by both tumors. Interestingly, GPx2 loss caused increases in a mesenchymal-like/quiescent and a highly proliferative luminal population, implying that GPx2 loss might drive a cancer stem-like population that is conducive of metastasis. Metascape pathway analysis of differentially expressed genes identified pathways that were significantly overrepresented in GPx2 knockdown tumors involving mitochondrial oxidative phosphorylation and response to hypoxia, consistent with the high levels of reactive oxygen species in these tumors. Finally, differential gene expression analysis on mesenchymal and luminal subpopulations predicts novel candidate gene signatures stimulated by GPx2 loss, that might be used to identify or target metastatic cells in tumors. In sum, our data imply that oxidative stress conveys a metastatic phenotype via effects on tumor cell heterogeneity.
Citation Format: Zuen Ren, Malindrie Dharmaratne, Ameya Kulkarni, Atefeh Taherian Fard, Jessica Mar, Phillip M. Galbo, Yang Liu, Deyou Zheng, Huizhi Liang, Outhiriaradjou Benard, Kimita Suyama, Michael B. Prystowsky, Larry Norton, Rachel B. Hazan. Redox regulation of tumor cell heterogeneity in the PyMT mammary tumor model revealed by single cell RNA sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4426.