bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1935: Racial and ethnic disparities in survival among women with advanced-stage ovarian cancer who received systemic therapy: A National Cancer Database analysis
Authors: Washington Caretia J. , Karanth Shama D. , Braithwaite Dejana , Akinyemiju Tomi F. 
Published: April 2023

Abstract
Purpose: To evaluate the association between race and ethnicity and all-cause mortality among women with advanced-stage ovarian cancer who received systemic therapy.
Methods: We obtained data from the National Cancer Database on women diagnosed with advanced-stage ovarian cancer from 2004 to 2015. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) by race and ethnicity groups (non-Hispanic (NH)-White, NH-Black, Hispanic, NH-Asian/Pacific Islander, and Other) and to examine the association of race/ethnicity with survival, stratified by age and comorbidity while adjusting for clinical and demographic variables.
Results: There were 53,367 women (52.4% ages ≥ 65 years, 8.7% NH-Black, 5.7% Hispanic, and 2.7% NH-Asian/Pacific Islander) included in the analysis. NH-Black women had a higher risk of death compared to NH-White women (HR: 1.13; 95% CI: 1.07,1.18), while Hispanic women had a lower risk of death compared to NH-White women (HR: 0.89; 95% CI: 0.82,0.97). The Black-White disparity persisted for women ages &lt; 65 years and ≥ 65 years, and among women with no comorbidities (HR:1.14; 95% CI: 1.08,1.21).
Conclusion: Among women with advanced-stage ovarian cancer who received systemic therapy, NH-Black women experienced decreased survival compared with NH-White women, regardless of age and comorbidity status. Additional research is essential to identify drivers of ovarian cancer disparities, including racial differences in treatment response.
Citation Format: Caretia J. Washington, Shama D. Karanth, Dejana Braithwaite, Tomi F. Akinyemiju. Racial and ethnic disparities in survival among women with advanced-stage ovarian cancer who received systemic therapy: A National Cancer Database analysis [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 1935.
Abstract 2069: ScNanoGPS: A robust tool for simultaneous calculation of same-cell genotypes and phenotypes from single cell long read transcriptomes
Authors: Shiau Cheng-Kai , Lu Lina , Kieser Rachel , Fukumura Kazutaka , Pan Timothy , Lin Hsiao-Yun , Yang Jie , Tong Eric L. , Lee GaHyun , Yan Yuanqing , Huse Jason T. , Gao Ruli 
Published: April 2023

Abstract
Single-cell Nanopore sequencing of full-length mRNAs is transforming single-cell multi-omics studies. However, challenges include computational complexity and dependence on short-read curation. To address this, we developed a comprehensive toolkit, scNanoGPS to compute same-cell genotype and phenotype without short-read guidance. We applied scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell lines. Standalone, scNanoGPS accurately deconvoluted error-prone long reads into single cells and single molecules. Further, scNanoGPS simultaneously accessed both phenotypes (expressions/isoforms) and genotypes (single nucleotide variants) of individual cells. Our analyses revealed that tumor and stroma/immune cells often expressed significantly distinct combinations of isoforms. In a kidney tumor, we identified 924 genes with distinct combinations of isoforms involved in cell-type-specific functions such as PDE10A in tumor cells and CCL3 in lymphocytes. Moreover, transcriptome-wide mutation analyses identified many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting critical roles of different populations in tumors. In summary, scNanoGPS facilitates applications of single-cell long-read sequencing.
Citation Format: Cheng-Kai Shiau, Lina Lu, Rachel Kieser, Kazutaka Fukumura, Timothy Pan, Hsiao-Yun Lin, Jie Yang, Eric L. Tong, GaHyun Lee, Yuanqing Yan, Jason T. Huse, Ruli Gao. ScNanoGPS: A robust tool for simultaneous calculation of same-cell genotypes and phenotypes from single cell long read transcriptomes [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 2069.
Abstract 2070: Accelerated somatic mutation calling tool for whole-genome and whole-exome sequencing data from heterogenous tumor samples
Authors: Ji Shuangxi , Zhu Tong , Sethia Ankit , Montierth Matthew D. , Wang Wenyi 
Published: April 2023

Abstract
As constantly improving in capacity and reducing in price, genomic sequencing is becoming a routine part of medical practice for cancer patients. Variant calling in sequencing data is a fundamental prerequisite for any downstream analysis, thus playing a critical role in both basic research and clinical care of cancers. However, it remains notably time-consuming for most available tools (e.g., ~2 days for MuSE 1.0 and MuTect2 to complete running on one tumor-normal pair of whole-genome sequencing (WGS) data). Here, we launch MuSE 2.0, which maintains the same input and output as our previously released MuSE 1.0, but speeds up significantly for both whole-exome sequencing (WES) and WGS data. MuSE 2.0 employs a multithreaded producer-consumer model and the OpenMP library for parallel computing, including parsing and uncompressing reads from BAM files, detecting and filtering variants, and writing output. Using sample data from ICGC and TCGA, we have benchmarked the speed performance of MuSE 2.0 against MuSE 1.0, MuTect2, SomaticSniper and VarScan2, which are chosen as the somatic mutation callers in the GDC DNA-seq analysis pipeline (https://docs.gdc.cancer.gov/Data/Bioinformatics_Pipelines/DNA_Seq_Variant_Calling_Pipeline/). Compared to MuSE 1.0, MuSE 2.0 with 80 cores reduces the time cost of SNV calling from ∼40 hours per pair of tumor-normal WGS data down to less than 1 hour, and from 2-4 hours per pair of tumor-normal WES data down to 4-5 minutes (~50-60 times speedup). It is also faster than three other methods (up to 60 times), i.e., MuTect2, VarScan2 and SomaticSniper, for both WGS and WES data. These results show that MuSE 2.0 is a time-efficient tool and is expected to remove somatic mutation calling as a time-consuming obstacle for cancer genomic studies and clinicians decision making. MuSE 1.0 was adopted in multiple large-scale pipelines, including as a major contributing caller to reach final consensus calls by the TCGA PanCanAtlas project across 13,000 tumor samples, and the ICGC Pan-Cancer Analysis of Whole Genomes (PCAWG) initiative across 2,700 tumor samples. We therefore expect MuSE 2.0 to significantly accelerate the variant calling process and benefit the scientific and clinical communities. MuSE 2.0 is implemented in C++ and is freely available at GitHub https://github.com/wwylab/MuSE.
Citation Format: Shuangxi Ji, Tong Zhu, Ankit Sethia, Matthew D. Montierth, Wenyi Wang. Accelerated somatic mutation calling tool for whole-genome and whole-exome sequencing data from heterogenous tumor samples [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 2070.
Abstract 2077: Spatial analyses methods for visualization and interrogation of tumor immune micro-environment using multiplexed images
Authors: Kewale Vidhya , Das Komal 
Published: April 2023

Abstract
Immunotherapies are new and promising treatments but work only for a small subset of patients. IHC staining is the current standard technique for diagnosing and a commonly used research technique but only allows for evaluation of one, or maximum two, biomarkers at a time. Multiplexed immunofluorescence assays and multispectral imaging technology can label up to six biomarkers on the same tissue section to capture the tumor-immune tissue environment complexity at the single-cell level. These images are very data-rich, but the crowding of information on the tissue can make it difficult to derive meaning directly from the multiplexed images. Current commercial and open-source software has the capability to segment each cell and quantify each biomarker; however, there are not yet any computational tools to capture spatial relationships. With R programming, we developed a toolkit to quantify and visualize multiplexed imaging data for detailed quantification and spatial analysis. Using our computational toolkit, novel questions about the tissue behavior can be addressed, such as tissue heterogeneity, different cell types, cell functional status (naïve, exhausted, experienced, etc.), spatial visualization and quantification of expression level of biomarkers across the tissue, proximity and interaction of different cell types at the single cell level, and much more. We plan to release this toolkit as a web-based R-Shiny app to allow biologists and clinicians to upload their multiplexed imaging data and choose combinations of cell characteristics they would like to analyze. The power of multiplex imaging is the detailed spatial data it provides, and our data analytics methods can be used to effectively extract relevant information about single-cell level relationships.
Citation Format: Vidhya Kewale, Komal Das. Spatial analyses methods for visualization and interrogation of tumor immune micro-environment using multiplexed images [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 2077.
Abstract 2165: Identification and characterization of Karyopherin α2 (KPNA2), a member of the nucleocytoplasmic transporter family, in lung cancer
Authors: Kim Seoree , Lee Heejin , Yoon Jung-Sook , Lee Hyun Woo , Kang Seok Yun , Lee Ji Hyun , Chun Sang Hoon , Won Hye Sung , Hong Soon Auck , Kang Keunsoo , Ahn Young-Ho , Ko Yoon Ho 
Published: April 2023

Abstract
Introduction: Many oncologists began to make sense, that the Karyopherin a-2 (KPNA2), a nucleocytoplasmic transport protein, regulates the nuclear import of macromolecules and changes in cellular phenotype. In particular, it can be a poor prognostic marker by causing aberrant subcellular localization of DNA damage response proteins or OCT4-c MYC pathway molecules depending on the type of carcinoma. An association with the p53 oncogenic pathway has been reported, showing good prognostic values in other types. We aimed to investigate the clinical significance and metabolic pathway of stable CAF and cancer cells for KPNA2
Method: We retrospectively analyzed the data from NSCLC patients receiving curative resection in Uijeongbu and Bucheon St. Mary’s Hospitals (n=165). IHC staining was performed on the tumor microarray samples using antibodies against KPNA2. The positivity was defined as median value of H-score.
Result: Based on the TMA staining, mean KPNA2 score was 36.5 [0-240] and median value was 10. Table 1. Scatter plots and correlation between KPNA2 expression levels and tumor invasiveness markers reveals that high KPNA2 expressor was related to lymphatic invasion (p = 0.00782), advanced stage (p = 0.0202) and current smoker (p = 0.0074). KPNA2 expression was higher in squamous cell carcinoma(SqCC) histotype than in adenocarcinoma (SqCC ratio (%), 13.5 vs 43.4 in Low exp vs High exp; p = 0.007). Patients with high expression of KPNA2 showed shorter survival than other patients (median OS (mo), 72.8 vs 42.2, P &lt; 0.0001; median RFS (mo), 72.8 vs 32.1, P &lt; 0.0011) and relevant to high recurrence (recurrence rate (%), 24.7 vs 44.7, p = 0.007).
Conclusion: Taken together, our results suggest that KPNA2 protein expression has a poor prognostic association, revealed by its association with survival outcome or invasiveness markers. Its clinical significance as an oncogenic target molecule is emerging, and further evaluation using an organoid model is in progress.
Baseline clinical and pathological characteristics
Citation Format: Seoree Kim, Heejin Lee, Jung-Sook Yoon, Hyun Woo Lee, Seok Yun Kang, Ji Hyun Lee, Sang Hoon Chun, Hye Sung Won, Soon Auck Hong, Keunsoo Kang, Young-Ho Ahn, Yoon Ho Ko. Identification and characterization of Karyopherin α2 (KPNA2), a member of the nucleocytoplasmic transporter family, in lung cancer [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 2165.
Abstract 2350: Role of ECM hyaluronic acid in the tumor-promoting functions of TIMP-1
Authors: Thorenoor Nithyananda , Xiao Wei , Rojiani Amyn M. , Rojiani Mumtaz V. 
Published: April 2023

Abstract
Non-small cell lung carcinoma (NSCLC) is responsible for the most significant number of lung cancer deaths with over 85% of lung cancers falling in this category. The dismal outcomes of this disease are augmented by advanced disease at initial presentation and ongoing development of chemoresistance following standard chemotherapeutic interventions. Tissue Inhibitor of metalloproteinase-1 (TIMP-1), one of the natural inhibitors of matrix degrading enzymes, is classically regarded as a tumor suppressor. However, there is much evidence that has established this molecule as having tumorigenic functions and has been shown to be upregulated in multiple cancers as well as in the development of fibrosis. In earlier studies we have demonstrated the tumor-promoting role of TIMP-1 in multiple biological interactions including angiogenesis, apoptosis, chemoresistance and cancer metabolism in NSCLC. The ECM plays an important role in providing structural support and as a depot for growth factors and cytokines critical for cell signaling. As TIMP-1 remains a vital molecule facilitating and modulating multiple elements of the ECM, we have sought to further define its role in the tumor microenvironment ECM in NSCLC cells. Our investigations have shown that TIMP-1 protein accumulates in the culture medium over long incubation periods. We have also found TIMP1 mRNA upregulation during this incubation period and correlated this as a function of cell density. As high cell density led to increased upregulation of TIMP1 mRNA, we postulated that factors secreted in the culture were responsible for this upregulation. We have identified that hyaluronic acid (HA), a component of the ECM, was accumulating in the culture media, resulting in the above response. HA is a critical matrix molecule of the tumor pericellular stroma and its upregulation is associated with poor prognosis. It is synthesized by hyaluronic acid synthetase (HAS) isoforms 1,2 and 3. We have also found that HAS2 was strongly expressed in high TIMP1 expressing NSCLC cells. Several studies have shown increased HAS2 expression in tumor tissue. We found that knocking down TIMP1 resulted in lower HA levels and decreased expression of HAS2. In a 3D coculture spheroid assay utilizing A549 cells and MRC5, we have shown increased expression of TIMP-1 and HA, which was also confirmed in archived NSCLC patient samples. The role of HA in the tumor-promoting functions of TIMP1 will be discussed further.
Citation Format: Nithyananda Thorenoor, Wei Xiao, Amyn M. Rojiani, Mumtaz V. Rojiani. Role of ECM hyaluronic acid in the tumor-promoting functions of TIMP-1 [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 2350.
Abstract 2352: ALDOC interplays with KIAA1409 to reduce m6A modifications and cancer-associated fibroblast characteristics in gliomas
Authors: Li Chien-Hsiu , Chan Ming-Hsien , Chang Yu-Chan 
Published: April 2023

Abstract
The abundance and regulatory mechanisms of tumor microenvironment in gliomas remain unclear. We have previously demonstrated that aldolase c (ALDOC) has tumor suppressor function and prognostic value in the progression of glioma. In this study, we used immune infiltration algorithms to identify the immune response events that ALDOC modulates in gliomas and found that they were particularly strongly associated with cancer-associated fibroblasts (CAFs). Our transcriptomic and proteomic profiles infer that ALDOC is involved in the methylation status of N6-methyladenosine (m6A) and binds to KIAA1429, which in turn affects the assembly of the assembly of the m6A-METTL complex. We show that ALDOC can interact with KIAA1429 and trap it in the cytoplasm and then interfere with the modification of m6A. In malignant cells and ALDOC knockdown models, we observed loss of ALDOC function, KIAA1429 was responsible for the ‘writer’ of m6A and stabilized expression levels of various CAF-related features. Through the MeRIP-Seq/m6A-seq approach, we found that the RNA-binding protein, IGF2BP2, can be directly stabilized with multiple CAF-related genes. We examined ALDOC and KIAA1429, CAF-related genes (FAP, α-SMA, S100A4 and VIM) in available cohorts and tissue microarrays and were statistically inversely correlated. Furthermore, ALDOC colocalized with KIAA1429 and CAF genes in the surrounding microenvironment was significantly reduced in tissue sections from orthotopic animal models by multiplex immunohistochemistry.
Keywords: Aldolase C, m6A modification, cancer-associated fibroblasts, gliomas
Citation Format: Chien-Hsiu Li, Ming-Hsien Chan, Yu-Chan Chang. ALDOC interplays with KIAA1409 to reduce m6A modifications and cancer-associated fibroblast characteristics in gliomas [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 2352.
Abstract 2353: PTGES is involved in the myofibroblast differentiation
Authors: Yang Yi-Fang , Lee Yi-Chen , Lin Min-Hsi 
Published: April 2023

Abstract
Lung cancer is the leading cause of cancer-related death worldwide, and patients usually have poor prognoses and low 5-year survival rates. Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both chronic and dysfunction of lung refers to lung fibrosis and increased risk of lung cancer. Myofibroblasts contribute to the procession of asthma, COPD, and IPF, leading to fibrosis of the airway and lung. Accumulating evidence has shown metabolic reprogramming has been considered a major hallmark of fibrosis and plays an important role in the fibrosis process. In this study, we identified Prostaglandin E Synthase (PTGES) was upregulated in lung fibroblast after being treated with IL-4, IL-13, and TNF-α, respectively. We found that PTGES increased the levels of myofibroblast markers α-SMA, FAP, and Vimentin, and promoted lung fibroblast cell migration and invasion. Further, in vivo lung fibrosis model demonstrated that PTGES was upregulated in lung fibrosis rats. PTGES induces phosphorylation of ERK1/2 and HIF-1α expression in lung fibroblast cells. Based on our findings, PTGES increases the expression of myofibroblast markers to modulate the myofibroblast differentiation.
Citation Format: Yi-Fang Yang, Yi-Chen Lee, Min-Hsi Lin. PTGES is involved in the myofibroblast differentiation [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 2353.
Abstract 2355: Transcription factor EB modulates fibrotic response in pancreatic ductal adenocarcinoma
Authors: Alcalde Alejandra Diaz , Vallariello Edoardo , Astanina Elena , Middonti Emanuele , Bussolino Federico 
Published: April 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC), which comprises 85% of all the pancreatic cancers, is one of the most aggressive and deadly tumor that exists today with less than 8% of survival 5 years after diagnosis. It is predicted to become the second cause of cancer death by 2030. A typical characteristic of this tumor is the presence of prominent stroma component mainly produced by Pancreatic Stellate Cells (PSCs) in response to soluble factors released by cancer cells. PSCs activation and differentiation into CAF (Cancer-associated fibroblasts) is a reversible process, which impacts on both tumor progression and drug resistance. Transcription factor EB (TFEB) is mostly known as a master regulator of autophagy and lysosomal biogenesis. A recent study demonstrated that TFEB inhibits epithelial-to-mesenchymal transition (EMT) and myofibroblast differentiation in epicardial cells by upregulating TGIF1, a TGFβ pathway repressor. Based on this observation, we investigated if TFEB might have an inhibitory role in PSCs activation, taking into consideration the crucial role of TGFβ signaling in this process. The TFEB expression, measured by immunostaining, was significantly downregulated in CAFs in human PDAC samples compared to PSCs in healthy pancreas. In PSCs, co-cultured with PDAC cell lines, CAF markers were upregulated while TFEB expression was downregulated. The overexpression of TFEB in PSCs suppressed CAF markers upregulation induced by co-culture with PDAC cells at both mRNA and protein levels. The bulk RNAseq analysis showed the differential expression of genes required for extracellular matrix production, fibrotic response and inflammation in PSCs co-cultured with PDAC cell lines versus PSCs alone, with and without TFEB overexpression. These in vitro data suggest a role for TFEB in PSCs activation and stroma formation which will be further investigated in PDAC mouse models.
Citation Format: Alejandra Diaz Alcalde, Edoardo Vallariello, Elena Astanina, Emanuele Middonti, Federico Bussolino. Transcription factor EB modulates fibrotic response in pancreatic ductal adenocarcinoma [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 2355.