bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2207: The prognostic role of γδ T cells in colorectal cancer and the establishment of related nomogram for predicting overall survival of the patients
Authors: Ma Rulan , Xue Dangcheng , Zhang Yong , Zhu Kun , Yuan Dawei , Sun Tuanhe , Mo Caijing , Deng Xiaoyuan , Qin Fujun , Li Kang 
Published: June 2023

Abstract
Objective: The aim of the present study was to explore the prognostic role of γδ T cells in colorectal cancer, and establish a nomogram for predicting the overall survival of the patients.
Methods: Immunohistochemistry was performed to analyze the infiltration degree of γδ T cells in tumor and normal tissues of colorectal cancer. The relationship between γδ T cells infiltration in tumor tissues and the prognosis of patients with colorectal cancer were determined by survival analysis. Cox regression analysis was performed to detect the factors related to the prognosis of patients with colorectal cancer. R software was used to establish and verify a nomogram for predicting the prognosis of patients with colorectal cancer.
Results: The degree of γδ T cell infiltration in tumor tissues and normal tissues of CRC was not different (t=0.35, P=0.731). However, the infiltration of γδ T cell was related to the survival status of the patients (x2=4.88, P=0.027). Besides, the infiltrating degree of γδ T cells in tumor tissue was obviously related to the prognostic improvement of the patients with colorectal cancer (Log-rank P=0.016) and could reflect the benefit of adjuvant chemotherapy (Log-rank P=0.003). Cox regression analysis showed that tumor stage (HR:3.14, 95%CI:1.25-7.89, P=0.015), serum CEA level (HR:3.67, 95%CI:1.48-9.10, P=0.005) and γδ T cell infiltration (HR:0.38, 95%CI:0.14-0.99, P=0.049) were independent prognostic factors of overall survival in patients with colorectal cancer. A nomogram based on tumor stage, serum CEA level and γδ T cell infiltration was established and showed a good prediction ability for survival of patients with colorectal cancer.
Conclusion: γδ T cell infiltration degree in tumor tissue was an important factor to improve the outcome of patients with colorectal cancer, and could predict the benefit of adjuvant chemotherapy. The nomogram had a good ability for predicting overall survival of the patients with colorectal cancer.
Citation Format: Rulan Ma, Dangcheng Xue, Yong Zhang, Kun Zhu, Dawei Yuan, Tuanhe Sun, Caijing Mo, Xiaoyuan Deng, Fujun Qin, Kang Li. The prognostic role of γδ T cells in colorectal cancer and the establishment of related nomogram for predicting overall survival of the 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 2207.
Abstract 2214: NEDD9 as a prognostic biomarker and its immune landscape in lung adenocarcinoma
Authors: Al-Kraimeen Leen M. , Al-Kraimeen Yaqeen M. 
Published: June 2023

Abstract
Introduction: Lung adenocarcinoma (LUAD) is the deadliest cancer worldwide. Many efforts are made to search for new biomarkers to screen for immunotherapy candidates and predict the response. Neural Precursor Cell Expressed, developmentally down-Regulated 9 (NEDD9), is predominantly expressed in many cancer types but has not been studied yet in lung adenocarcinoma. Herein, we analyzed the association of NEDD9 with immune inhibitory components to understand its immune landscape in lung adenocarcinoma.
Methods: Gene expression profiles were retrieved from The Cancer Genomic Atlas Lung Adenocarcinoma cohort (n = 567). We used TIMER 2.0 for immune inhibitory cell infiltrates analysis. Tumor mutational burden (TMB) was measured using the cBioPortal tool. The enrichment analysis of function and signaling pathways of DEGs in LUAD was done by gene ontology (GO) using Enrichr.
Results: NEDD9 is differentially expressed in LUAD tissues (P &lt; 0.00). High NEDD9 expression had better overall survival prognostic value in LUAD patients (HR: 0.66, 95% CI: 0.49 - 0.89, P = 0.0221) compared to low expression. NEDD9 expression was positively correlated with the infiltration of cancer-associated fibroblasts and macrophage M2 cells (spearman’s ρ = 0.257, P &lt; 0.001, ρ = 0.266, P &lt; 0.001, respectively), but negatively with myeloid-derived suppressor cells (MDSC) (ρ = -0.344, P &lt; 0.001). Moreover, survival analysis based on NEDD9 expression and MDSC levels revealed a better OS group identified by low MDSC levels and low NEDD9 expression after adjustment for age, stage, and purity. In terms of immune checkpoint genes’ expression, NEDD9 expression was directly correlated with CTLA-4, PD-1, PD-L1, VSIR, and LAG-3 (ρ &gt; 0.2, Q value &lt; 0.05). TMB was inversely associated with NEDD9 expression (ρ = -0.1, P &lt; 0.001). GO analysis showed that genes co-expressed with NEDD9 were mainly in the phagocytic vesicles and participated in biological processes of cellular response to interferon-gamma by molecular function such as cysteine-type endopeptidase activity involved in apoptotic signaling pathways.
Conclusion: We found that NEDD9 expression is a useful biomarker of immunosuppression in LUAD patients and can predict the response to immunotherapy. Our results suggest that NEDD9 is a favorable prognostic biomarker, which could be explained by low MDSC. Further studies are needed for a better understanding of the NEDD9 value in LAUD.
Citation Format: Leen M. Al-Kraimeen, Yaqeen M. Al-Kraimeen. NEDD9 as a prognostic biomarker and its immune landscape in lung 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 2214.
Abstract 2282: Immune modulation of the T cell repertoire in mice following immunotherapy and chemotherapy combination treatments
Authors: Elhanati Yuval , George Mariam M. , Choi Hyejin , Maniyar Rachana , Hamadane Linda , Mohibullah Neeman , Greenbaum Benjamin D. , Merghoub Taha 
Published: June 2023

Abstract
Background: Immune checkpoint blockade therapeutics have revolutionized cancer therapy. However, most patients are either unresponsive or develop acquired resistance. Understanding patient-specific temporal T cell repertoires in the context of immune interventions will contribute to a better understanding of potential improvement strategies for better T cell anti-tumor immunity. Current methods to understand the T cell repertoire changes over time are limited due to the limited amount of material and prohibitive cost. In this study, we designed and performed longitudinal TCR sequencing in mice treated with multiple therapies.
Methods: C57BL/6 mice were used in each treatment group, with blood drawn overtime before, during and after treatment. Mice were treated with a combination of immunotherapeutic agents and OVA peptide immunization, 100µl blood was drawn at multiple pre-, on- and post-treatment time points followed subsequently by TCR sequencing. Cyclophosphamide (CTX) is known to cause lymphodepletion followed by homeostatic proliferation. Thus, we also treated B16-F10 tumor bearing mice with CTX, and performed TCR sequencing on blood draws pre-, on-, and post-treatment to track TCR clone diversity and clonality over time.
Results: We find that our method is sensitive enough to detect effects of immunotherapies on TCR diversity in small sample quantities. Using our method, we discovered that certain immunotherapeutic agents, most evidently CD40, have a significant but transient effect on the diversity of the T cell repertoire. We observed an initial increase in repertoire clonality, seven days post CD40 treatment followed by contraction. We show how we can identify antigen specific T cells and follow reacting T cell clones. In addition, we find that CTX treatment is associated with increased clonality in tumor bearing mice particularly in the week following treatment reflecting changes in the TCR repertoire.
Conclusion: We have developed a method by which we can follow the TCR repertoire in mice treated with immunotherapy or chemotherapy. This enabled us to isolate and study the effects of different immune modulatory drugs of the endogenous T cell repertoire overtime.
Citation Format: Yuval Elhanati, Mariam M. George, Hyejin Choi, Rachana Maniyar, Linda Hamadane, Neeman Mohibullah, Benjamin D. Greenbaum, Taha Merghoub. Immune modulation of the T cell repertoire in mice following immunotherapy and chemotherapy combination treatments [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 2282.
Abstract 2291: Dynamics of genomic instability of circulating tumor DNA in pancreatic cancer patients
Authors: Heo SooBeen , Chun Jung Won , Cho Eun-Hae , Lee Tae-Rim , Ki Chang-Seok , Kim Yun-Hee , Woo Sang Myung , Kong Sun-Young 
Published: June 2023

Abstract
Background: Genomic instability of circulating tumor DNA (ctDNA) has been evaluated as a prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). However, we did not investigated the association of dynamics between baseline and follow-up genomic instability level and patients outcome.
Methods: CtDNA I-score which low-depth whole-genome wide copy number alterations calculated by Z-score comparing the relative frequency for each bin with healthy control were investigated in total 87 PDAC patients (N=32 in resectable stage and N=55 in metastatic stage). Follow-up period for resectable and metastatic patients was different after one month, and 2 and 4 months, respectively. Then the association between I-score dynamics at follow-up and survivals (progression free survival (PFS) and overall survival (OS)) were analyzed.
Results: The mean I-score represented as 7.212 (6.887 ± 0.073 in 32 resectable patients and 7.536 ± 0.123 in 55 metastatic patients, p &lt; 0.01) at baseline. In recetable patients, I-score decreased upto 6.710±0.03 (p=0.03) after 1 month and dynamics (decrease or increase) of I-score did not showed significant association with PFS and OS with hazard ratio (HR) of 3.6 (range 0.16-79.2 95% Cl) and 3.9 (range 0.3-50.7), respectively. I-score of metastatic patients at 2 and 4 moths were decresed to 7.180±0.062 (p= 0.01) and 7.029±0.056 (p &lt; 0.01). The change of I-score represented association with PFS and OS as HR 2.8 (range 0.9-8.5) and 0.5 (range 0.11-2.20) at 2 months and 1.1 (range 0.2-5.5) and 3.3 (range 0.07-142.7) at 4 months, respectively.
Conclusion: Overall I-score decreased after treatment in both resectable and metastatic patients. To investigate impact for outcome of dynamics of genomic instability in ctDNA, we will continue to analyze follow-up data for long term results.
Citation Format: SooBeen Heo, Jung Won Chun, Eun-Hae Cho, Tae-Rim Lee, Chang-Seok Ki, Yun-Hee Kim, Sang Myung Woo, Sun-Young Kong. Dynamics of genomic instability of circulating tumor DNA in pancreatic 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 2291.
Abstract 2293: Tumor-informed fixed and patient-specific panels for minimal residual disease (MRD) detection in early-stage NSCLC:a head-to-head comparison
Authors: Zhang Pengpeng , Gong Zetian , Yu Yue , Wang Xiaoxuan , Ye Lei , Wang Xiaoqiang , Tang Xuan , Zhang Chao , Deng Wanglong , Song Chao , Xu Qing , Li Yansong , Wang Wei 
Published: June 2023

Abstract
Introduction: Detection of minimal residual disease (MRD) by ctDNA based on tumor-informed or tumor-naive strategy could be used as an effective method to predict the relapse of NSCLC. As for tumor-informed strategy,both fixed panel and patient-specific panel are promising methods in MRD monitoring. Patient-specific panel can be used to monitor tissue specific somatic mutations individually. Besides, fixed panel can make up for the deficiency caused by organizational heterogeneity. In this study, we compared the monitoring effect of novel tumor-informed fixed and patient-specific panels.
Methods: 81 patients with stage I-III resected NSCLC were analyzed, including 45 patients (55.6%) with stage I, 15 (18.5%) with stage II and 21 (25.9%) with stage III. Tumor samples were obtained at surgery. Preoperative blood samples (baseline) were analyzed by both tumor-informed fixed and patient-specific panels based on hybrid capture. Tumor-informed fixed panel was performed by using ultra-deep (60000X) next-generation sequencing with 158 gene panel spanning 118 kb of human genome. Patient-specific panel was also performed by using ultra-deep (100000X) next-generation sequencing with customized 40 single nucleotide variants identified using whole-exome sequencing.
Results: Tumor-informed fixed panel monitored 212 mutations (median, 3; range, 0-7). Most of them (95.3%) were matched in the corresponding tumor tissues. For patient-specific panels, 91% of patients were customized design 40 mutations, affected by the detection of tissue somatic mutations. Based on fixed or patient-specific panel, ctDNA mutations were detected in 46.9% vs 49.4% (P=0.75) at baseline, respectively (Stage I: 35.6% vs 37.8%, P= 0.83; Stage II: 53.3% vs 60%, P=0.71; Stage III: 66.7% vs 66.7%).
Conclusions: Both tumor-informed fixed and patient-specific panel NGS assay can detect the presence of ctDNA in early-stage NSCLC. However, the detection rate of preoperative ctDNA mutations was slightly higher based on patient-specific panel.
Citation Format: Pengpeng Zhang, Zetian Gong, Yue Yu, Xiaoxuan Wang, Lei Ye, Xiaoqiang Wang, Xuan Tang, Chao Zhang, Wanglong Deng, Chao Song, Qing Xu, Yansong Li, Wei Wang. Tumor-informed fixed and patient-specific panels for minimal residual disease (MRD) detection in early-stage NSCLC:a head-to-head comparison [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 2293.
Abstract 2294: The development of 3D deformable microfilter with a DNA aptamer for detecting circulating tumor cell
Authors: Iwatsuki Masaaki , Nakashima Yuta , Kitamura Yusuke , Yasuda Keiichiro , Baba Hideo 
Published: June 2023

Abstract
Introduction: The analysis of blood for circulating tumor cells (CTCs) has opened new avenues for cancer diagnostics, including early detection, risk assessment and staging. However, research about CTCs has been challenging due to the rarity of CTCs in bloodstream. We develop a three-dimensional deformable microfilter with a EpCAM aptamer for detecting CTCs and conduct a pilot study to evaluate the efficacy of our novel detection devise.
Methods: The cancer cell suspension with blood from healthy volunteers and human blood sample from cancer patients are passed through the microfilter and counted by fluorescence microscope. We also countered the number of cancer cells by CellSearch eq \o\ac(○,R)R. The peripheral blood sample from upper gastrointestinal cancer patients are also passed through the microfilter.
Results: Even in the presence of 100 times normal cell, cancer cells were captured on the substrate successfully from cell suspensions with several mixing ratios. We can capture cancer cells suspended with PB from healthy volunteer more effectively compared with CellSerach®. A total of 15 patients and 40 samples were enrolled (Stage I: II: III: IV: recurrence=1:1:3:4:6). The average number of CTCs was 3.1 cells/ml (0-6.3 cells). Among the 15 patients with GC, CTCs were detected by our system in 13 patients. Even in GC patients suspected with peritoneal dissemination without definitive mass by imaging, CTCs were successfully detected. For the patients who were measured multiple times with clinical time course, we found a close correlation between CTC number and CEA level or image assessment.
Conclusion: We successfully detected CTCs in the patients with upper gastrointestinal cancer patients. Although our pilot study indicates the potential of a novel devise to capture CTC effectively, a large scale of validation is needed to confirm the clinical utility.
Citation Format: Masaaki Iwatsuki, Yuta Nakashima, Yusuke Kitamura, Keiichiro Yasuda, Hideo Baba. The development of 3D deformable microfilter with a DNA aptamer for detecting circulating tumor cell [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 2294.
Abstract 23: Development of a biallelicDicer1mutant mouse strain for studying the pathogenesis of DICER1 syndrome-associated cancer
Authors: Wang Yemin , Chen Shary , Senz Janine , Douglas Maxwell , Thornton Shelby , Moscovitz Yana , Gilks C. Blake , Huntsman David , Morin Gregg 
Published: June 2023

Abstract
DICER1 encodes a RNase III enzyme that post-transcriptionally controls gene expression through governing microRNA (miRNA) biogenesis. We and others have demonstrated that somatic mutations of DICER1 at its RNase IIIb domain metal binding sites, impairing its capability to produce mature miRNAs from the 5P strand of miRNA precursors, occur recurrently in a broad spectrum of cancers associated with the DICER1 syndrome that affects children and youths predominantly. The biallelic DICER1 mutations in these cancers challenge the two-hit hypothesis theory of traditional tumour suppressors, but it remains unproven whether these mutations are sufficient to drive tumorigenesis. The lack of biology relevant preclinical models has also hindered the understanding the pathogenesis. Here, we developed a genetically engineered mouse strain that expresses an inducible knockin Dicer1 missense mutation (Dicer1+/fl-D1693N), equivalent to the DICER1 RNase IIIb hotspot mutation D1709N in human cancers. This conditional strain behaves as a null allele due to an aberrant splicing event without Cre-mediated recombination. When crossed with a well-characterized conditional null Dicer1 strain (Dicer1fl/fl), the resulting compound heterozygous strain (Dicer1fl/fl-D1693N), acts as a hemizygous wildtype allele that is converted to a hemizygous missense mutation allele upon Cre-mediated recombination, reflecting the genetic status of DICER1 in DICER1 syndrome-associated cancer. When crossing with the anti-Mullerian hormone receptor 2 (Amhr2) driven cre strain (Amhr2+/cre), the biallelic Dicer1 mutation resulted in infertility in females by impairing the development of oviduct and endometrium and ultimately drove the development of multicystic tubal and intra-uterine tumours. Histologically, these murine tumors resemble human Müllerian adenosarcoma and other DICER1 syndrome-associated sarcomas. Molecular analysis of these murine tumours validated the miRNA biogenesis defects in 5P-miRNA production, uncovered the activation of the myc signaling and identified that loss of let-7 family miRNAs may drive the transcriptomic rewiring and malignant transformation. Thus, this first DICER1 syndrome-associated murine cancer model faithfully recapitulates the biology of human cancer and provides a unique tool for future investigation and therapeutic development.
Citation Format: Yemin Wang, Shary Chen, Janine Senz, Maxwell Douglas, Shelby Thornton, Yana Moscovitz, C. Blake Gilks, David Huntsman, Gregg Morin. Development of a biallelicDicer1mutant mouse strain for studying the pathogenesis of DICER1 syndrome-associated 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 23.
Abstract 2312: Single-cell low pass whole genome sequencing for copy-number profiling in circulating tumor cells from prostate, non-small cell lung and breast cancers
Authors: Wang Danyi , Locatelli Giuseppe , Gounaris Ioannis , Scheuenpflug Juergen , Feng Zheng 
Published: June 2023

Abstract
Background: Circulating tumor cells (CTCs) have been considered as an alternative to tissue biopsy for providing both germline-specific and tumor-derived genetic variants. Copy number variations (CNVs) play an important role in molding the genomes of cancers and have been shown the clinical value for prognostic signature and therapeutic target. The current study aimed to evaluate CNVs at single-cell resolution and explore the potential clinical utility of tracking this key mechanism of cancer progression.
Methods: Blood samples were collected in Streck tubes from 40 stage II-IV cancer patients (5 prostate cancer, 15 non-small lung cancer (NSCLC), 20 breast cancer (BC)) before treatment. CTCs was identified as cells containing an intact nucleus, without CD45 expression, and with cytokeratin expression. Genomic analysis of chromosomal CNVs by low pass whole genome sequencing (Lp-WGS) and number of large-scale transitions (LSTs) calculation was performed in the CTCs.
Results: A total of 9 CTCs from 4 prostate cancer, 70 CTCs from 7 NSCLC, 22 CTCs from 9 breast cancer patients, representing a range of sizes, shapes, and protein expression levels of cytokeratin were identified. A total of 84 individual CTCs were successfully sequenced from 20 patients (1-6 CTCs/patient). The selected highlights for gene CNVs include: 1) CXCR4 and ATM were detected as loss on single cell CTC (scCTC) level in BC; 2) MED12, an important regulator for maintaining accurate cytokinesis and survival, was detected as loss on scCTC level in NSCLC. A wide range of LST scores were observed among the 20 patient samples. Cell morphology analysis, phenotypic heterogeneity biomarker analysis and homologous recombination deficiency (HRD) biomarker analysis using a previously developed HRD classifier1 trained on genomic markers is still ongoing.
Conclusion: Our data demonstrated that Lp-WGS of DNA from CTCs can detect CNVs loss and assess disease heterogeneity at the single-cell level. Since genome-wide CNV profiles can be used to characterize genomic instability, it is anticipated that the integrative analysis of morphology and genomics in CTCs can potentially complement tissue and/or ctDNA analysis to determine HRD, enabling in-depth investigation of tumor heterogeneity and individualized clinical assessment.
Citation Format: Danyi Wang, Giuseppe Locatelli, Ioannis Gounaris, Juergen Scheuenpflug, Zheng Feng. Single-cell low pass whole genome sequencing for copy-number profiling in circulating tumor cells from prostate, non-small cell lung and breast 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 2312.