bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6404: Clinical scenario of immune checkpoint inhibitor treatment in metastatic nasopharyngeal carcinoma
Authors: Hsu Cheng-Lung , Kuo Yung-Chia 
Published: April 2023

Abstract
Advanced in local treatment technology and early detection methodology, distant metastasis became a critical issue in Nasopharyngeal carcinoma (NPC). Recently, cancer immunotherapy especially immune checkpoint inhibitors (ICIs) including anti-programmed death-1 (PD-1) and PD-1 ligand (PD-L1) monoclonal antibodies (Mabs) had a rapid progress in cancer patient management. We try to clarify the clinical scenario of immune-related parameters in metastatic NPC. We had check 81 metastatic tissue PD-L1 expression without ICI treatment from the tissue bank of CGMH, Linkou, during 2005~2019. Using anti-PD-L1 antibody, 22C3 Dako, tumor proportional score (TPS) was positive in 43.2% (35/81) checked tissue and combine positive score (CPS) was positive in 58.0% (47/81) tissue respectively. For overall survival (OS) combined with PD-L1 expression in metastatic tissue analysis, positive CPS but not TPS correlated with longer survival with statistical significance (TPS: &gt;0% vs =0%, median survival, 24m vs 22.5m, p=0.615186; CPS: &gt;0% vs =0%, median survival, 28m vs 16m, p=0.003709). Retrospectively analysis of metastatic NPC treatment of combination of chemotherapy, ICIs, and local treatment in our institute in the past 6 years, total 40 patients was enrolled with median overall survival of 34.1 months. Objective response rate by RECIST criteria for immunotherapy-based regimen was 75% (CR:40%; PR:35%) and disease control rate was 85%. According to response by RECIST criteria, median overall survival were 34.1 months vs. 16.7 months respectively for responders and non-responders. With pre-treated NLR as cutoff value of 1.6, difference of median overall survival between two groups (responder vs nonresponder) was statistically significant (p=0.021). We also found that lower median post-treatment NLR in responders than in non-responders (1.4 vs. 3.2, p=0.013). Using rapid lymphocyte amplification protocol via IL-2 stimulation, the PBMC from most of the patient received ICIs treatment can be amplified 1~10 folds and positively correlated with total lymphocyte count. Through flowcytometry analysis, we found these amplified PBMC was lymphocyte dominant and rich in CD8+. We also found these amplified PBMC can kill the NPC EBV-positive cell line and xenograft in vitro and in vivo. These results demonstrated that combination of chemotherapy, ICIs, and local treatment will benefit metastatic NPC patients.
Citation Format: Cheng-Lung Hsu, Yung-Chia Kuo. Clinical scenario of immune checkpoint inhibitor treatment in metastatic nasopharyngeal 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 6404.
Abstract 6497: Availability of healthcare providers and its association with survival outcomes in non-Hodgkin lymphoma in the United States
Authors: Gaddam Shiva Jashwanth , Grewal Udhayvir Singh , Hassan Zara , Ramadas Poornima 
Published: April 2023

Abstract
Background: Survival outcome in Non-Hodgkin lymphoma (NHL) is significantly better in earlier stages, compared to advanced stages. Early identification of signs and symptoms, and prompt specialist availability and referral, are crucial for diagnosis and treatment at earlier stages. Mounting physician shortages are a growing concern, and we sought to analyze their effect on NHL mortality rates.
Methods: We extracted data on the age-adjusted mortality rate (AAMR) and crude incidence rate (CIR) of NHL for all U.S. states and the District of Columbia from the Center for Disease Control (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database (2017-2019). Nevada was excluded due to missing information. Data on the state-wise number of primary care physicians (PCPs) was obtained from the Association of American Medical Colleges (AAMC) state physician workforce data report (2020), and of Hematology/Oncology specialists (HOs) was gathered from the National Provider Identifier (NPI) registry (2020). The number of PCPs and HOs per each NHL incidence (PCP/CIR, HO/CIR respectively) was then calculated. Correlations were analyzed using Pearson’s coefficient. Statistical analysis was performed using VassarStats.
Results: Median AAMR for NHL in the US was 5.15 (IQR 4.35, 5.95) per 100, 000 population. The median number of PCP and HO per each case of NHL incidence was 4.32 (IQR 3.43, 5.21), and 0.28 (IQR 0.1, 0.37) respectively. States with fewer PCPs per each NHL incidence had higher AAMR (r=-0.37, p=0.007). States with a lower number of HOs per each NHL incidence had higher AAMR (r=-0.41, p=0.003)
Conclusions: Based on the analysis, the availability of a lower number of PCPs and HOs per each NHL incidence is associated with increased AAMR of the disease. This data may strengthen the need for intensification of focus on decreasing the soaring physician shortages in the states, in order to help decrease the overall mortality associated with NHL.
Citation Format: Shiva Jashwanth Gaddam, Udhayvir Singh Grewal, Zara Hassan, Poornima Ramadas. Availability of healthcare providers and its association with survival outcomes in non-Hodgkin lymphoma in the United States [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 6497.
Abstract 6531: Point of care test for cervical cancer screening
Authors: Habbani Samrin Farouk Idris , Dowlatshahi Sayeh Jalali , Elumalai Monisha , Bolton Scott Charles , Tecle Lucy Teberh , Thakkar Pankti Rajesh , Linnes Jacqueline C , Mohammed Sulma I 
Published: April 2023

Abstract
Cervical cancer is a lethal gynecological malignancy and the fourth most common cancer among women. Most high-grade cervical pre-cancers and cancer cases are linked to infection with high-risk human papillomaviruses (HPV). There is an inequity between high-income countries (HICs) and low- and middle-income countries (LMICs) in cervical cancer burden; according to the World Health Organization, the estimated mortality rate of cervical cancer is 342,000 women worldwide in 2020, and 90% of these women reside in low- and middle-income nations where the human papillomavirus vaccine is unavailable and access to early detection testing are either unavailable or too expensive. This study aims to develop a simple and affordable point-of-care test based on four critical biomarkers for screening high-risk pre-cancer and invasive cervical cancer in collaboration with the biomedical engineering department. A cervical cancer swab will be used in the test. The swab will be placed on a paper-based device that looks for four protein biomarkers critical for the progression of noninvasive cervical cancer into invasive cervical cancer by combining two approaches using proteomics and lateral flow immunochromatography technology. We have validated the markers' expression in cervical cancer and precancerous tissues. The four markers were expressed in squamous cell carcinoma, glassy cell carcinoma, adenocarcinoma, clear cell carcinoma cancer tissues, and the high-grade cervical intraepithelial neoplasia. This point-of-care test will be affordable and implementable, especially in low and middle-income countries.
Citation Format: Samrin Farouk Idris Habbani, Sayeh Jalali Dowlatshahi, Monisha Elumalai, Scott Charles Bolton, Lucy Teberh Tecle, Pankti Rajesh Thakkar, Jacqueline C Linnes, Sulma I Mohammed. Point of care test for cervical cancer screening [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 6531.
Abstract 6539: Application of optical genome mapping to identify samples with homologous recombination deficiency
Authors: Pang Andy Wing Chun , Chang Kelsea , Sahajpal Nikhil , Saul Daniel , Kolhe Ravindra , Chaubey Alka , Hastie Alex 
Published: April 2023

Abstract
Certain cancer treatments, such as the poly (ADP-ribos) polymerase (PARP) inhibitors, have been shown to be effective in killing cancer cells exhibiting genome instability signatures indicative of homologous recombination deficiency (HRD). Hence, these signatures are used as biomarkers to inform treatment decisions and prognosis. There are three measurements of HRD signatures commonly employed: loss of heterozygosity (HRD-LOH), telomeric allelic imbalance (TAI) and large-scale state transition (LST). It has been shown that combining all three scores can better determine the HRD phenotype, leading to a higher clinical impact. Yet current HRD signature tests, used to estimate HRD, have low negative predictive value, and one possible reason is that current genomic technologies lack sensitivity to capture the full extent of somatic genomic rearrangements. Here, optical genome mapping (OGM) was used to detect large structural variants (SVs) and calculate a HRD score. OGM captures high molecular weight DNA to call SVs by aligning these molecules to the public reference genome. OGM can comprehensively detect insertions and deletions &gt;5kbp, inversions, interchromosomal translocations, plus large interstitial copy number variation (CNV) and aneusomies. Subsequently, an automated script was developed to compute the HRD score, which is the summation of the three HRD signatures: HRD-LOH, the number of regions with a loss &gt;15 Mbp but shorter than the whole chromosome; TAI, the number of regions of gain and loss &gt;10Mbp that extend to a subtelomere but do not cross the centromere; and LST, the number of chromosomal breakpoints whose SV size &gt;10Mb but not the whole chromosome. We applied this script on 20 samples of solid tumors and myeloid neoplasms, and the automated scores are concordant with expertly curated scores, confirming the validity of the calculation. We believe that OGM data combined with this automated analysis of HRD signatures is much more sensitive and accurate for detection of HRD signatures and that this will enable more precise prediction of drug response for multiple tumor types.
Citation Format: Andy Wing Chun Pang, Kelsea Chang, Nikhil Sahajpal, Daniel Saul, Ravindra Kolhe, Alka Chaubey, Alex Hastie. Application of optical genome mapping to identify samples with homologous recombination deficiency [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 6539.
Abstract 6575: LinkedOmicsKB: A web portal to explore pan-cancer molecular and phenotype associations
Authors: Savage Sara R. , Liao Yuxing , Dou Yongchao , Shi Zhiao , Yi Xinpei , Jiang Wen , Lei Jonathan T. , Zhang Bing 
Published: April 2023

Abstract
Pan-cancer multi-omics data produced from integrated genomic, epigenomic, transcriptomic, proteomic, and post-translational modification (PTM) profiling of a wide variety of cancer types holds great potential for understanding cancer biology and generating therapeutic hypotheses. To realize this potential and make analysis and visualization of these complex and interconnected data easily accessible to cancer biologists and clinicians, we have developed a web portal, LinkedOmicsKB. The web portal provides access to a harmonized proteogenomic dataset of over 1000 patient samples covering 10 cancer cohorts from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). We calculated associations between methylation, copy number variation (CNV), RNA, protein, and phosphosite data for each gene and further correlated the proteogenomics data with clinical and computed molecular phenotypes. All results are stored in a MongoDB database and visualizations are provided for exploring pan-cancer multi-omics relationships as well as individual statistics. We demonstrate the utility of LinkedOmicsKB to provide insights into clinical phenotypes, somatic mutations, and understudied genes. In the pan-cancer CPTAC data, overall survival was correlated with proteins involved in protein hydroxylation, including PLOD1 and PLOD2. Additionally, two phosphorylation sites on the tumor suppressor MIG-6 were associated with worse survival. These sites were also associated with hypoxia, MAPK, and EGFR pathway activity scores, suggesting a relationship between the signaling in these pathways and cancer prognosis. STK17B is an understudied kinase that regulates apoptosis. We found STK17B was upregulated in 6 cancer types at the protein level but only two at the RNA level. The protein abundance of STK17B was highly associated with immune scores and JAK/STAT signaling, supporting a role for STK17B in the immune response. We identified 3 phosphorylation sites on STK17B, which were associated with EGF pathway activity scores and immune-related scores. LinkedOmicsKB is a valuable tool that can be used to generate biological and clinical insights into any gene, phosphosite, mutation, or phenotype.
Citation Format: Sara R. Savage, Yuxing Liao, Yongchao Dou, Zhiao Shi, Xinpei Yi, Wen Jiang, Jonathan T. Lei, Bing Zhang. LinkedOmicsKB: A web portal to explore pan-cancer molecular and phenotype associations [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 6575.
Abstract 6588: Systems biology-based drug repositioning and biomarker discovery for Thai liver fluke-associated cholangiocarcinoma
Authors: Jamnongsong Supawan , Kueanjinda Patipark , Tawornparcha Piyathida , Vaeteewoottacharn Kulthida , Okada Seiji , Jirawatnotai Siwanon , Pongpaibul Ananya , Korphaisarn Krittiya , Sampattavanich Somponnat 
Published: April 2023

Abstract
Our group has recently reported the successful use of comprehensive drug response and pan-omic profiling for identifying repurposable drug shortlists in Asian cholangiocarcinoma. We also developed the CCA45 gene-expression signature that could accurately predict the prognosis of CCA patients, especially those with Asian ethnic backgrounds. To further explore therapeutic candidates and potential resistance mechanisms, we have established CCA1 cell lines resistant to their subgroup-specific drug candidates: MEK and SRC inhibitors. Reverse-phase protein arrays (RPPA)-based proteomic profiling revealed upregulation of cell cycle, apoptosis, MAPK, and mTOR-related proteins in both MEKi- and SRCi-resistant cells. Src pathway activity was found to be more significantly reduced in SRCi-resistant cells. We identified CDK4/6 inhibitors as the second-line therapeutic candidates for MEK inhibitor-resistant cells by systematic drug screening. SRCi-resistant cells unexpectedly developed cross-resistance to MEK inhibitors and showed sensitivity to only a few CDK4/6 inhibitors. These data are beneficial for the clinical translation of our proposed drug candidates for Asian CCA, preparing the alternate regimens after drug resistance. We also adopted the DSP-based spatial transcriptomic platform to compare the tumor microenvironment between chemotherapy-sensitive and chemotherapy-resistant CCA patients. While the CTA panel showed consistent patterns of normalized gene expression to those of the WTA panel, the CTA panel can only measure 17 of the 45 genes required for our CCA45 signature. Out of these 17 genes, ITGB4, FGFR3, VEGFC, NOTCH1, and RRAD showed significant gene expression changes with reducing tumor percentage. The microenvironment of gemcitabine/cisplatin responder (R) non-responder (NR) exhibited negative regulation of ERK1/2 and MAPK, high WNT pathway activity, and high tumor-infiltrating lymphocyte (TIL). In contrast, the microenvironment of the non-responder (NR) subgroup showed high neutrophil-related activity, high NFκB, high Treg, and the exhausted immune phenotype. Overall, our study contributes toward realizing the precision medicine concept for CCA patients.
Citation Format: Supawan Jamnongsong, Patipark Kueanjinda, Piyathida Tawornparcha, Kulthida Vaeteewoottacharn, Seiji Okada, Siwanon Jirawatnotai, Ananya Pongpaibul, Krittiya Korphaisarn, Somponnat Sampattavanich. Systems biology-based drug repositioning and biomarker discovery for Thai liver fluke-associated cholangiocarcinoma [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 6588.
Abstract 6596: Genomic and proteome analysis using preoperative cell free DNA and extracellular vesicles of lung cancer patients
Authors: Koba Hayato , Kimura Hideharu , Yano Seiji 
Published: April 2023

Abstract
Background: The detection of circulating cell free DNA (cfDNA) has been examined as a predictor of postoperative recurrence and survival in lung cancer patients. Extracellular vesicles (EVs) have potent for searching a new target to cancers.
Objective: To analyze the association between cfDNA/EVs and prognosis after lung cancer surgery.
Methods: We retrospectively examined patient background, disease-free survival, overall survival, and preoperative cfDNA in lung cancer patients who underwent surgery at Kanazawa University Hospital between January 2017 and May 2020, in whom preoperative chemotherapy was not administered. We extracted cfDNA from 4 ml plasma within 7 days before surgery and measured its concentration. EVs were extracted from 500 μl serum via Tim4 protein. Proteins included in EVs were analyzed by mass spectrometry.
Results: 285 patients were included, 179 males and 106 females, median age 71(36-88) years, and 8 patients had SCLC. EGFRm- positive lung cancer was included in 93 cases (32.6%). The pStage0/l/ll/lll/lV of NSCLC was 7/187/42/36/6 respectively, and the pStagel/ll/lll of SCLC was 4/1/3 respectively. The mDFS of NSCLC was 14.6 (7.8-29.7)/21.5 (8.5-NA) months in pStage lll/lV, respectively. mOS was 53.3 (28.7-NA) months in pStage lll and was not achieved in other stages. The mDFS of SCLC was 19.8 (1.9-NA)/NA/5.7 (1.9-NA) months in pStage l/ll/lll, respectively. mOS was NA/NA/9.3 (9.3-NA) months, respectively. cfDNA was detected in 283 (99.2%) patients, with a concentration of 4.7 (0-60.0) ng/μl. The correlation coefficient between cfDNA concentration and DFS/OS in NSCLC was -0.023 (P=0.70)/-0.014 (P=0.81). The correlation coefficient between cfDNA concentration and DFS/OS for SCLC was -0.86 (P=0.024)/-0.89 (P=0.012). No recurrence was observed in patients in whom cfDNA was not detected.EVs were detectable from pre-operative serum samples, and the proteins included in these were different, whether disease was recurrent or not.
Conclusion: The cfDNA concentration did not correlate with DFS/OS in post-operative NSCLC, whereas it correlated negatively with DFS/OS in SCLC. In the presentation, we will further discuss about the concrete genetic alterations and protein expression, based on the cfDNA sequencing and proteomics analysis.
Citation Format: Hayato Koba, Hideharu Kimura, Seiji Yano. Genomic and proteome analysis using preoperative cell free DNA and extracellular vesicles of lung cancer patients [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 6596.
Abstract 6599: Neomer and fragmentation profiles of cell-free DNA with low-pass whole genome sequencing to predict prostate cancer biopsy outcomes
Authors: Liu Fei , Peng Kaoqing , Chen Rui , Li Mingzhao , Zeng Tao , Zhao Yan , Wang Ming , Liu Hongxing , Wu Jianhao , Wu Min , Tang Haimeng , Bao Hua , Wu Xue , Shao Yang , Gu Di , Ren Shancheng 
Published: April 2023

Abstract
Prostate cancer is one of the most common types of cancer in men. Current prostate-specific antigen (PSA)-based diagnostic strategy for prostate cancer may frequently cause overdiagnosis. In this study, we prospectively recruited 380 individuals, including 167 with pathologically confirmed prostate cancer, 127 with negative prostate biopsy results, and 86 assessed healthy cohort with no need for biopsy. We collected a plasma sample from each participant, performed whole-genome sequencing, and profiled cell-free DNA (cfDNA) neomer and fragmentation characteristics. We then developed a machine learning model using these cfDNA profiles to predict prostate cancer biopsy outcomes. Our results showed that this assay could achieve high accuracy (Accuracy: 85.3%, AUROC: 0.919, 95% CI: 0.892 - 0.946) in repeated 5-fold cross validations. Patients with negative biopsy results had higher prediction scores than healthy individuals (P &lt; 2.2X10-16), making them less distinguishable from prostate cancer patients (AUROC: 0.878, 95% CI: 0.837 - 0.918 vs. AUROC: 0.980, 95% CI: 0.963 - 0.997). We further combined this cfDNA-based assay with the PSA testing and constructed an ensemble model. The classification performance was further improved in the ensemble model, showing AUROC metrics of 0.951 (95% CI: 0.932 - 0.969) between cancer and non-cancer, 0.919 (95% CI: 0.889 - 0.949) between cancer and negative biopsy, and 0.998 (95% CI: 0.994 - 1.000) between cancer and healthy individuals. At a sensitivity of 90.4%, the ensemble assay accurately identified 85.4% of non-cancerous conditions, including 76.4% of negative biopsy patients and 98.8% of healthy individuals. We concluded that our cfDNA fragmentation and neomer-based assay could be incorporated into the PSA-based predicting system for prostate cancer to increase the accuracy and reduce the overdiagnosis.
Citation Format: Fei Liu, Kaoqing Peng, Rui Chen, Mingzhao Li, Tao Zeng, Yan Zhao, Ming Wang, Hongxing Liu, Jianhao Wu, Min Wu, Haimeng Tang, Hua Bao, Xue Wu, Yang Shao, Di Gu, Shancheng Ren. Neomer and fragmentation profiles of cell-free DNA with low-pass whole genome sequencing to predict prostate cancer biopsy outcomes [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 6599.