bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3165: ImmuneSig: A deep learning framework to develop gene expression signature of immune checkpoint inhibitor therapy
Authors: Liu Yang , Jhaveri Aashna , Bodapati Sudhenshna , Wong Cheryl , Michor Franziska 
Published: June 2023

Abstract
Immune checkpoint inhibitor (ICI) therapy targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD1), and programmed death-ligand 1 (PDL1) induces durable remission in some patients with various cancer types. Given the variable patient outcomes, many studies have been conducted to identify prognostic biomarkers associated with ICI response. However, due to intra- and inter-tumor heterogeneity and the complexity of the immune system, those biomarkers have diverse efficacy for predicting outcomes in clinical trials. Here we propose a deep learning framework with unsupervised self-learning autoencoders that identifies predictive features from patient transcriptomics data. This approach allows us to determine the contribution of each gene to the response classifier and identifies potential gene signatures for predicting immunotherapy response by using the learned weights of trained autoencoders. We applied our framework to 20+ ICI clinical cohorts across different cancer types and compared the prediction performance of our method with other well-known immune response markers evaluated using a suite of machine learning algorithms (random forest, logistic regression, and XGboosting) with cross-validation. We found that in some cohorts, the learned features from autoencoders improve the predictive power of ICI response when evaluated with the area under the operating characteristic curve. Our framework uncovers potential immune gene signatures associated with patient outcomes. Our work will help advance cancer immunology and immuno-oncology research, provide insights into tumor immunity, and lead to the discovery of progressively more immune markers and novel immune targets.
Citation Format: Yang Liu, Aashna Jhaveri, Sudhenshna Bodapati, Cheryl Wong, Franziska Michor. ImmuneSig: A deep learning framework to develop gene expression signature of immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3165.
Abstract 3327: Proteomic profiling of extracellular vesicles in patients with biliary tract cancers
Authors: Kim Dong Uk , Park Sunghee , Han Sung Yong , Jeon Daye , Lee Hyeji , Lee Jonghyun , Nam Hyeong Seok , Lee Dong Wook , Cho Chang-Min , Jung Min Kyu , Heo Jun , Kang Un-Beom , Park Seong-Jun , Huh Sunghyun , Shin Yourae 
Published: June 2023

Abstract
Background and Aim: Biliary tract cancers (BTCs) have a poor prognosis. One of the reasons for the prognosis is the difficulty of early diagnosis. The absence of a sufficient biomarker to screen for BTCs in high-risk populations makes the patient to be recognized in advanced status. Therefore, it is urgent to discover a biomarker for early detection of BTCs. This study analyzed extracellular vesicle (EV) peptides to find a new serum biomarker of BTCs.
Methods: Plasma samples were obtained from 5 healthy people as control, 10 from patients with benign biliary diseases such as choledocholithiasis, sclerosing cholangitis, and gallbladder polyp, and 29 from BTCS patients. The EV peptides have been obtained from 2.5ml of patient plasma. The EV peptide samples were analyzed by liquid chromatography-data-dependent acquisition-tandem mass spectrometry (LC-DDA-MS/MS). The acquired peptides and proteins were investigated by searching in Fragpipe-MSFragger. Characterization was performed using the EVs database of previous studies. After that, Differential Expression Protein (DEP) analysis and Pathway/GO analysis are performed to know the biological process.
Results: Total 25,382 peptides and 3,313 proteins were defined (PSM, peptide-level FDR 1%). Most of the gene ontology biological processes were related to vesicle-mediated transport. On DEP analysis, total 72 proteins were up-regulated, and 29 proteins were down-regulated. Compared to cancer samples, 9 proteins were up-regulated to both healthy and benign samples and 2 were down-regulated. According to biological process/pathway analysis, up-regulated 9 proteins were mostly related to cytoskeleton/ECM and Hemostasis. Down-regulated 2 proteins were related to endocytosis and immunity.
Conclusions: By analyzing EV peptides, a total of 11 proteins have been identified. With validation experiments, we expect to finalize biomarker candidates.
Citation Format: Dong Uk Kim, Sunghee Park, Sung Yong Han, Daye Jeon, Hyeji Lee, Jonghyun Lee, Hyeong Seok Nam, Dong Wook Lee, Chang-Min Cho, Min Kyu Jung, Jun Heo, Un-Beom Kang, Seong-Jun Park, Sunghyun Huh, Yourae Shin. Proteomic profiling of extracellular vesicles in patients with biliary tract cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3327.
Abstract 3343: Liquid biopsy screening tool for the earlier detection of brain tumors
Authors: Theakstone Ashton G. , Brennan Paul M. , Baker Matthew J. 
Published: June 2023

Abstract
Background: There is a need for a rapid, cost-effective and non-invasive screening tool for the earlier detection and diagnosis of brain tumors. Serum based ATR-FTIR combined with machine learning algorithms can reliably predict which patients with symptoms will actually have a tumor on brain imaging. This technique gives a broad overall serum composition of the patient. However, an approach combining spectroscopy and specific cytokines within the serum could potentially provide a more accurate detection and permit prediction of tumor subtypes before histological diagnosis.
Method: Patient serum samples (300uL) were collected prospectively from patients with a new brain tumor diagnosis, and patients without a brain tumor as non-cancer controls. Each patient was analysed using both ATR-FTIR and an electrochemical approach targeting specific cytokine markers. MMP-3, MMP-9 and osteopontin were selected from an unsupervised screening of 64 cytokines. The patients were discriminated using machine learning techniques in three approaches; spectral data alone, biomarker data alone and the combination of both spectral and biomarker data. Receiver operator characteristic (ROC) curve analysis was completed to display the discriminatory ability of each approach.
Results: The spectral and biomarker data was collected for 49 patient samples (25 non-cancer, 24 GBM). All three approaches gave excellent discriminatory ability between cancer and non-cancer control patients. The spectral profiles alone had an area under the curve (AUC) of 0.958, the biomarker data alone had an AUC of 0.937 and the combination of spectral and biomarker data for each patient had an AUC of 0.975. The clinical datatset is being expanded to include more patients and this paper will discuss further patient analysis as well.
Conclusion: The combination of using patient data from both the spectroscopic and electrochemical approaches improved the discrimination between cancer and non-cancer patients. The addition of specific marker information could support prioritization for brain imaging, and prediction of tumor subtype to guide pre-operative management decision-making.
Citation Format: Ashton G. Theakstone, Paul M. Brennan, Matthew J. Baker. Liquid biopsy screening tool for the earlier detection of brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3343.
Abstract 3345: Tissue of origin (TOO) localization using targeted methylation biomarkers discovered by whole-genome bisulfite sequencing
Authors: Wei Qiang , Deng Wanglong , Xu Zhihui , Han Yihui , Yang Yuan , Zhang Chao , Wang Xiaoqiang , Tang Xuan , Song Chao , Xu Qing , Ren Yong 
Published: June 2023

Abstract
DNA methylation is a promising biomarker for tissue of origin (TOO) localization, which is important for classification of cancer of unknown primary site (CUP) in multiple cancer early detection. The current most of CpG sites of TOO focused on CpG islands based on The Cancer Genome Atlas (TCGA) data sets, but remains largely under-explored across the whole genome. In this study, we conducted the whole-genome bisulfite sequencing (WGBS) in 481 tumor samples and 361 matched adjacent normal tissue samples for 9 common types of cancers, including lung, breast, colon, liver, stomach, lymph, pancreas, esophageal and ovarian. After adjusted the tumor cells’ DNA methylation rates, 3,000 CpG sites, 60% of which were not on CpG islands, were selected through Random Forest classifier (multi-class) to identify cancer type. To evaluate these TOO methylation biomarkers, we used Random Forest Model to predict TOO of the methylation data sets in The Cancer Genome Atlas (TCGA), including 1,704 tumor samples. The results showed that accuracy of TOO could achieve 98.5% for these tumor samples of TCGA. Among these samples, the accuracy of TOO of breast, liver, lung, colorectal and pancreas were 99.6%, 99.9%, 97.7%, 99.2% and 99.3% respectively. Several samples from Esophagus and Stomach were classified to each other, and their accuracy of TOO was relatively low, 97.6% and 96.7%. It demonstrated that these methylation biomarkers could detect multiple cancers, and the multi-class model had good performance for TOO localization.
Citation Format: Qiang Wei, Wanglong Deng, Zhihui Xu, Yihui Han, Yuan Yang, Chao Zhang, Xiaoqiang Wang, Xuan Tang, Chao Song, Qing Xu, Yong Ren. Tissue of origin (TOO) localization using targeted methylation biomarkers discovered by whole-genome bisulfite sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3345.
Abstract 3383: Liquid biopsy for PDL-1 status by analysis of cfRNA: Clinical data from a large community practice
Authors: Hart Lowell L. , Bergh Magali Van den 
Published: June 2023

Abstract
PD-L1 testing via immunochemistry has become a widely used tool to predict response to immune checkpoint inhibitor (ICI) therapy in many tumor types. However this marker can be expressed heterogeneously, and can vary with time, treatment effects, and local factors including cytokine expression. Gene expression profiles of immunologically active genes are currently being studied to more accurately predict response to ICI treatment. To evaluate a potentially more straightforward way to accomplish this, we utilized an assay of cfRNA in plasma for PD-L1, utilizing a real-time PCR based assay (Circulogene, Inc, Birmingham, AL). The demonstrated limit of detection for PD-L1 RNA was 1 copy/ul. Results were reported as either not detected, or low at over 1%, or high at over 50%. We used the PCR 30th percentile Ct value corresponding to a tissue IHC PD-L1 of&gt;50%, and the 66th percentile Ct value corresponding to a tissue PD-L1 expression of &gt;1%. We then collected data on over 400 patients over a two year period at a large community oncology practice and at a university clinic (Florida Cancer Specialists and Atrium Health/Wake Forest-Baptist Comprehensive Cancer Center) who had a clinical necessity for molecular testing in a commercially available setting with a CLIA certified lab. In some cases the corresponding tissue PD-L1 testing was also available, and may have been either positive or negative.To date 41 patients have been found to have high levels of cfRNA for PD-L1. Their clinical course has been analyzed using the electronic medical record. Some patients have received standard of care therapy, and some have been given CPI therapy with or without chemotherapy, if the attending oncologist felt this to be the best palliative option. These include tumors such as CRPC, metastatic low grade neuroendocrine carcinoma and HR+ metastatic breast carcinoma, that have rarely been treated successfully with CPI therapy. Tumor types - all are stage IV solid tumor patients: 19 NSCLC, 7 breast carcinoma, 3 colorectal cancer, 3 castrate resistant prostate carcinoma, 9 other tumor types.Data collection for tumor response or clinical benefit on the 41 patients is ongoing and will be presented at the meeting, and compared to published CPI response data using standard tissue IHC testing.
Citation Format: Lowell L. Hart, Magali Van den Bergh. Liquid biopsy for PDL-1 status by analysis of cfRNA: Clinical data from a large community practice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3383.
Abstract 3387: ctDNA dynamics in early stage node negative lung cancers
Authors: Feng Jamie , Waddell Tom , Yasufuku Kazuhiro , Pierre Andrew , Keshavjee Shaf , Yeung Jonathan , Cypel Marcelo , Donahoe Laura , Wakeam Elliot , de Perrot Marc , Law Jennifer , Salvarrey Alexandra , Le Lisa W. , Lister Jennifer , Cabanero Michael , Tsao Ming , Pipinikas Christodoulos , Howarth Karen , Leighl Natasha 
Published: June 2023

Abstract
Introduction: Patients with early-stage lung cancers have a high risk of relapse and death even after curative surgery. Detection of circulating tumour DNA (ctDNA) in plasma perioperatively is associated with shorter recurrence free survival (RFS). ctDNA-Lung-Detect is an investigator-initiated prospective study of ctDNA detection and association with RFS in patients with early stage non-small cell lung cancer (NSCLC).
Methods: Patients with clinically staged T&lt;4cm N0 NSCLC planned for surgical resection at the Princess Margaret/University Health Network underwent ctDNA assessment before and after surgery (~1 month and 1 year). ctDNA minimal residual disease (MRD) was detected using the highly sensitive and specific tumor-informed Residual Disease and Recurrence (RaDaR®, Inivata, Cambridge, UK) assay, which can track up to 48 tumor-specific variants in plasma.
Results: Since August 2021, 64 eligible patients were enrolled (Table 1). One had isolated metastasis from a remote non-lung primary and subsequently excluded; another had their preoperative sample missed but was included. Preoperative ctDNA was detected in 15/62 (23.8%) patients and 1/63 (1.6%) post-operatively at the 1-month landmark timepoint (occult N2 disease found at surgery). All but one (93.3%) had ctDNA clearance with surgical resection. Two patients have recurred radiographically and in plasma at 1 year post-operatively, 1/15 with preoperative ctDNA detected (6.7%) and 1/47 without preoperative ctDNA detected (2.1%). Patients with higher T stage, tumor size, squamous histology, and without actionable driver alterations were more likely to have ctDNA detected at any timepoint.
Conclusions: In patients with early stage NSCLC (small node negative tumors), 24% have detectable ctDNA pre-operatively. Surgical resection led to ctDNA clearance in 93% of cases. Our results support ongoing testing beyond the initial MRD landmark. Assessment of the impact on RFS post resection is ongoing.
Citation Format: Jamie Feng, Tom Waddell, Kazuhiro Yasufuku, Andrew Pierre, Shaf Keshavjee, Jonathan Yeung, Marcelo Cypel, Laura Donahoe, Elliot Wakeam, Marc de Perrot, Jennifer Law, Alexandra Salvarrey, Lisa W. Le, Jennifer Lister, Michael Cabanero, Ming Tsao, Christodoulos Pipinikas, Karen Howarth, Natasha Leighl. ctDNA dynamics in early stage node negative lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3387.
Abstract 3591: Does the metastatic immunoenvironment determine poor immunotherapy responses
Authors: Barth Nicole D. , van Dalen Floris J. , Duran Camille , Karmakar Utsa , Mendive-Tapia Lorena , Kitamura Takanori , Verdoes Martjin , Condeelis John S. , Oktay Maja , Vendrell Marc , Brunton Valerie , Entenberg David 
Published: June 2023

Abstract
Despite new treatments, cancer remains the second leading cause of death worldwide with breast cancer being the most common type. Of these deaths, the majority are due to the formation of distant metastases. While new immunotherapies have shown some success in primary tumors, their efficacy in combating metastases has been lacking. Thus we aim to investigate the hypothesis that immune responses at the metastatic site contribute to limitations of current therapies.Within the last decade, new microscopy technologies now enable real-time visualization of immune responses at primary and secondary sites. Here, we present use of these microscope technologies, along with the development of novel probes to detect apoptotic cancer cells, to investigate the success of checkpoint inhibitors in the primary and secondary sites. We validate, in multiple in vitro and in vivo assays (including intravital imaging), that fluorescent cyclic amphipathic peptide probes specifically label cells undergoing therapy-induced cancer death. In addition, we introduce a newly developed fluorescent, enzyme-activatable, chemokine-conjugate capable of targeting defined macrophage subsets in live tumors. This chemokine-conjugate exploits the high expression of chemokine receptors (e.g. CCR2) and the activity of cysteine cathepsins in tumor associated macrophages to selectively target and eradicate them without affecting other macrophages or immune cells (e.g., neutrophils, T cells, B cells). This research will help to elucidate the role of combination therapy on the metastatic foci and will provide the first insights into the benefit and limitations of combination therapy on secondary site immune responses.
Citation Format: Nicole D. Barth, Floris J. van Dalen, Camille Duran, Utsa Karmakar, Lorena Mendive-Tapia, Takanori Kitamura, Martjin Verdoes, John S. Condeelis, Maja Oktay, Marc Vendrell, Valerie Brunton, David Entenberg. Does the metastatic immunoenvironment determine poor immunotherapy responses. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3591.
Abstract 3601: Tumor MK2 signaling regulates cell migration and invasion in head and neck squamous cell carcinoma
Authors: Okwuone Dakota D. , Morgan Deri , Smith Hannah M. , Millington Grace , Berggren Kiersten L. , Lominska Christopher E. , Thomas Sufi M. , Gan Gregory N. 
Published: June 2023

Abstract
Poor 5-year overall survival in head and neck cancer (HNC) can be attributed to high rates of locoregional and distant metastasis. We have previously demonstrated that high phosphorylation/activation of MAPK-activated protein kinase 2 (MK2), a stress-activated kinase directly downstream of p38 MAPK, in head and neck squamous cell carcinoma (HNSCC) is associated with worse overall survival and inhibition of the MK2 pathway enhances in vivo HNSCC radiosensitivity. Our prior work also demonstrates that radiotherapy-induced epithelial-to-mesenchymal transition (EMT) gene expression can be suppressed in cells when MK2 is inhibited. Several studies have shown that EMT plays a prominent role in HNSCC tumor invasion, treatment resistance, and locoregional metastases to lymph nodes. In this study, we investigate the impact of MK2 activity on HNSCC tumor progression by examining its contribution to cancer cell morphology. We used lentiviral-shRNA and the CRISPR-Cas9 system to knock down/out the MK2 gene in multiple human and murine HNSCC cell lines. We measured tumor cell migration and invasion in both classic 2D in vitro culture as well as with 3D spheroids. We performed unbiased analysis via RNAseq in human HNSCC cell lines comparing MK2 shRNA vs scramble cell lines. Substantial gene and pathway alterations were examined using a combination of immunoblot and RT-qPCR. Our data shows knocking down/out MK2 in HNSCC cells significantly diminishes cell migration and invasion in 2D and 3D in vitro culture assays. RNAseq analysis demonstrated loss of MK2 leads to a significant increase in many cell adhesion molecules, including E-cadherin, and a decrease in N-cadherin, suggesting a shift from mesenchymal to more epithelial phenotype. Furthermore, we note expression of multiple matrix metalloproteinases and EMT markers (i.e., Snail) are substantially reduced in MK2 shRNA and KO cell lines. These results indicate that the MK2 pathway is involved in HNSCC motility and invasion. We also observe the loss of MK2 contributes to a shift in the epithelial:mesenchymal ratio potentially by suppressing cancer EMT plasticity. All in all, this study provides evidence suggesting tumor MK2 activation mediates HNC progression.
Citation Format: Dakota D. Okwuone, Deri Morgan, Hannah M. Smith, Grace Millington, Kiersten L. Berggren, Christopher E. Lominska, Sufi M. Thomas, Gregory N. Gan. Tumor MK2 signaling regulates cell migration and invasion in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3601.
Abstract 3730: A new type of transcriptional reprogramming by an IRF4 mutation in lymphoma
Authors: Cauchy Pierre 
Published: June 2023

Abstract
Disease-causing mutations in genes encoding transcription factors (TFs) are a recurrent finding in hematopoietic malignancies and might involve key regulators of lineage adherence and cellular differentiation1-3. Such mutations can affect TF-interactions with their cognate DNA-binding motifs4,5. Whether and how TF-mutations impact upon the nature of binding to TF composite elements (CE) and influence their interaction with other TFs is unclear. Here, we report a new mechanism of TF alteration in human lymphomas with perturbed B cell identity. It is caused by a recurrent somatic missense mutation c.295T&gt;C (p.Cys99Arg; p.C99R) targeting the center of the DNA-binding domain of Interferon Regulatory Factor 4 (IRF4), a key TF in immune cell-differentiation and -activation6,7. IRF4-C99R fundamentally alters IRF4 DNA-binding, with loss-of-binding to canonical IRF motifs and neomorphic gain-of-binding to canonical and non-canonical IRF composite elements (CEs). Furthermore, IRF4-C99R thoroughly modifies IRF4 function, by blocking IRF4-dependent plasma cell induction, and up-regulating disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single arginine mutation creates a complex switch of TF specificity and gene regulation. These data open the possibility of designing specific inhibitors to block the neomorphic, disease-causing DNA-binding activities of a mutant transcription factor.
Citation Format: Pierre Cauchy. A new type of transcriptional reprogramming by an IRF4 mutation in lymphoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3730.