tbuckley/cabot-search huggingface dataset:
Abstract 7668: Novel pretreatment nomograms based on pan-Immune-inflammation value for predicting clinical outcome in patients with head and neck squamous cell carcinoma
Authors: Qian Chen, Xiang Li, Yanxia Bai, Yue Chen
Journal: Cancer Research (2024)

Abstract Background: The prognostic value of an effective biomarker, Pan-Immune-Inflammation Value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients. Methods: 161 HNSCC patients underwent radical surgery and 50 patients received chemoradiotherapy were enrolled retrospectively for development and external validation cohort, respectively. The cut-off of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). Results: Patients with higher PIV (≥123.3) experienced a worse DFS (HR: 5.01, 95% CI: 3.25-7.72, p&amp;lt;0.0001) and overall survival (OS) (HR: 5.23, 95% CI: 3.34-8.18, p&amp;lt;0.0001) compared to patients with lower PIV (&amp;lt;123.3), which was also consistent in the external cohort. Predictors of Model A included age, TNM stage, neutrophil-to-lymphocyte ratio (NLR) and PIV, and that of Model B included TNM stage, lymphocyte-to-monocyte ratio (LMR) and PIV. In comparison with TNM stage alone, the concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves of the nomograms demonstrated good calibration and discrimination, and the decision curve analysis (DCA) also showed satisfactory clinical utility in both internal and external validation. Conclusions: The nomograms based on PIV, a simple but forceful indicator, can provide intuitive and precise prognosis prediction of individual HNSCC patients after radical surgery or chemoradiotherapy. Citation Format: Qian Chen, Xiang Li, Yanxia Bai, Yue Chen. Novel pretreatment nomograms based on pan-Immune-inflammation value for predicting clinical outcome in patients with head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7668.
Abstract 790: Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis
Authors: Kanaka Dhuri, Houda Alachkar
Journal: Cancer Research (2024)

Abstract Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a significant precursor to hematological malignancies and is associated with several age-related diseases. Recent studies in relatively small disease specific cohorts have suggested that CHIP may exhibit variations among different races and between males and females raising intriguing questions about potential genetic and environmental influences. Understanding the differences in CHIP across races and between males and females may have implications for personalized cancer risk assessment and targeted therapeutic strategies. Methods: Patient’s data were obtained from the Cancer Therapy and Clonal hematopoiesis via cBioportal. The original study was designed to examine clonal hematopoiesis mutations that were found in blood samples obtained from 24,146 patients with non-hematological cancers and their tumor-blood pairs were analyzed using targeting sequencing data MSK-IMPACT (Memorial Sloan Kettering-IMPACT). The cohort consisted of 45.7% males and 54.3% females; including 6.8% Asians, 6.2% Blacks, and 76.3% Whites. We examined mutation frequencies among these racial groups and between genders, employing the two-sided Fisher's exact test and adjusting p-values for multiple comparisons. Differences were considered significant when both P value and Q values are less than 0.05. Results: DNMT3A mutations were substantially more prevalent in females than in males (38.94% vs 31.37%, p-value: &amp;lt;10−10, q-value: 6.19e−09), While ASXL1 mutations were more frequent in males than females (5.82% vs 2.69%, p-value: &amp;lt;10−10, q-value: 6.19e−09). In the racial cohorts with sufficient sample sizes, STAT5B and CSF1R mutations were most frequent in Asian (1.40% and 0.84%), followed by Black (0.98% and 0.24%) and White populations (0.29% and 0.09%), (p-value: 8.099e−04 and 7.490e−04, q-value: 0.0234 and 0.0232). Several other CHIP mutations were enriched in Black: RARA, SMAD2, CDKN1B, CENPA, CTLA4, EIF1AX, ELF3, MSI1, MYC, SOX17, AURKA. On the other hand, H3C1, H3C4, MYCL were enriched in the Asian cohort. Conclusion: Our analysis provides insights into the complex interplay of sex and racial factors in shaping CHIP mutation frequencies. As CHIP continues to gain recognition as a critical precursor to malignancies, understanding these variations contributes to refining our understanding of its underlying mechanisms and clinical implications. Citation Format: Kanaka Dhuri, Houda Alachkar. Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 790.
Abstract 791: Evaluation of BCR spike-in controls using DriverMap adaptive immune receptor (AIR) profiling technology
Authors: Alex Chenchik, Tianbing Liu, Mikhail Makhanov, Dongfang Hu, Khadija Ghias, Paul Diehl
Journal: Cancer Research (2024)

Abstract The DriverMap™ Adaptive Immune Receptor (AIR) repertoire profiling assay employs multiplex RT-PCR for comprehensive profiling of CDR3 or full-length receptor profiling of all variable heavy and light chains of T-cell receptors (TCR) and B-cell receptors (BCR) from either RNA or DNA. In this study, initiated by a U.S. Food and Drug Administration (FDA) consortium to compare performance of different BCR repertoire profiling technologies, we tested spike-ins in peripheral blood mononuclear cell (PBMC) RNA and DNA control mixtures prepared from nine different B-cell lines. We measured the sensitivity, linearity and accuracy of AIR RNA and DNA BCR profiling for the IGH, IGK and IGL chains of the spike-in controls. Our comprehensive analysis, encompassing CDR3 profiling and full-length receptor profiling (CDR1, CDR2, and CDR3) sequencing, revealed a 100X increase in sensitivity of detection of spike-in controls in RNA compared to the DNA assay. The high sensitivity of the full-length DriverMap AIR RNA assay allowed the detection of controls from all nine cell lines, with 8 out of 9 cell lines detected in the DNA assay, which demonstrates the robustness of the DriverMap AIR profiling technology. This study highlights the remarkable sensitivity of the AIR RNA assay in quantifying transcripts. This approach enables the detection of low-frequency BCR clonotypes, which is particularly advantageous when working with samples containing low numbers of B cells. Furthermore, our AIR DNA assay in combination with spike-in controls offers a quantitative tool for minimal residual disease (MRD) applications, providing accurate insight into cell numbers, which then facilitates tracking clonal expansion of immune cells. Citation Format: Alex Chenchik, Tianbing Liu, Mikhail Makhanov, Dongfang Hu, Khadija Ghias, Paul Diehl. Evaluation of BCR spike-in controls using DriverMap adaptive immune receptor (AIR) profiling technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 791.
Abstract 812: Association of obesity with the early onset and diagnosis of triple negative breast cancer in black women
Authors: Sarabjeet Kour Sudan, Amod Sharma, Kunwar Somesh Vikramdeo, Wade Davis, Cindy Nelson, Karan Singh, Ajay Pratap Singh, Seema Singh
Journal: Cancer Research (2024)

Abstract Breast cancer (BC) continues to be the most common cancer and the second leading cause of cancer-related death in American women. Furthermore, it affects Black women more adversely than their White counterparts, who experience an early disease onset, diagnosed more often with aggressive triple-negative breast cancer (TNBC) molecular subtype, and face greater mortality. The reasons for these disparities; however, are largely unknown. Here, using a retrospective dataset, we examined the association of body mass index (BMI) with BC early onset and diagnosis with specific molecular subtype in race-based distributions. Study cohort included 1085 BC patients, who visited University of South Alabama Health clinics between October, 2017 and March, 2022. Patients were divided into three BMI [(normal weight, NW (&amp;lt;24.9), overweight, OW (25-29.9), and obese, Ob (&amp;gt;30.0)], three age (&amp;lt;45 years, 45-65 years, &amp;gt;65 years), and four molecular subtypes [Luminal A (HR+, HER2-), Luminal B (HR+, HER2+), HER2 enriched (HR-, HER2+), and TNBC (HR-, HER2-) categories. The data show a higher prevalence of BC in Ob women (46%) than OW (27%) and NW (27%) women of all age groups and its incidence was much greater in Ob Black women (61%) than Ob White women (39%). Further, Black women had nearly twice higher diagnosis at an early age than White women. Moreover, Ob Black women had over 7- and 1.5-folds higher incidence of early onset BC than NW and OW Black women, respectively, whereas, early onset BC did not exhibit a correlative pattern in White women. Luminal A and TNBC subtypes were the most common in women with early onset BC and Black women exhibited more than twice incidence of TNBC (32%) compared to the White women (14%) of all ages. In contrast, incidence of luminal A subtype was less prevalent in Black (57.4%) than in White (72.6%) women. Interestingly, both luminal A and TNBC subtypes were also more prevalent in Ob women; however, the risk of being diagnosed with TNBC increased dramatically in Ob Black women compared to Ob White women. Together, these findings establish obesity as a major underlying cause of early onset BC and TNBC diagnosis in Black women, which could be targeted to diminish the BC disparity gaps. Citation Format: Sarabjeet Kour Sudan, Amod Sharma, Kunwar Somesh Vikramdeo, Wade Davis, Cindy Nelson, Karan Singh, Ajay Pratap Singh, Seema Singh. Association of obesity with the early onset and diagnosis of triple negative breast cancer in black women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 812.
Abstract 4280: Regulatory T cells contribute to tumor cell dissemination by extracellular matrix remodeling
Authors: Ailen Garcia-Santillan, Jessanne Y. Lichtenberg, He Shen, Mikhail G. Dozmorov, Amy L. Olex, Priscilla Y. Hwang, Paula D. Bos
Journal: Cancer Research (2024)

Abstract Regulatory T (Treg) cells function to enforce peripheral tolerance and are potent suppressors of tumor immunity. In breast cancer, we have shown that Treg cells promote tumor growth by favoring alternative activation of macrophages via suppression of IFN-γ. The tumor-associated extracellular matrix (ECM) is a key regulator of metastatic dissemination and is emerging as a critical regulator of tumor immunity. However, the reciprocal effects of the immune system on the ECM remain elusive. Using murine in vivo, ex vivo and bioengineering models we describe Treg cell-dependent changes in the tumor ECM that facilitate tumor cell movement and metastatic dissemination. Further, Treg cell-dependent matrisome signatures correlate with survival in human breast cancer samples. This work underscores a previously unrecognized role of Treg cells on the ECM that facilitates metastasis and is consistent with tissue Treg cell emergent function as critical regulators of tissue repair and cancer. Citation Format: Ailen Garcia-Santillan, Jessanne Y. Lichtenberg, He Shen, Mikhail G. Dozmorov, Amy L. Olex, Priscilla Y. Hwang, Paula D. Bos. Regulatory T cells contribute to tumor cell dissemination by extracellular matrix remodeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4280.
Abstract 4966: Machine learning and large language model approach to pancancer data elements
Authors: Andrew Niederhausern, Nadia S. Bahadur, Gary Wallace, Gilan E. Saadawi, John Philip
Journal: Cancer Research (2024)

Abstract Introductory Statement: The goal is to use machine learning (ML) and large language model (LLM) to augment the manual curation of cancer data elements. Introduction: Memorial Sloan Kettering Cancer Center (MSKCC) has ~100,000 cancer patients and counting with genomic testing. Clinicians use genomic data for research but lack clinical data to analyze together. We use a vendor, VASTA Global to hire curators to manually curate cancer patient’s core clinical data elements (CCDE) within unstructured/paragraph text in electronic medical record (EMR) notes. CCDE encompasses 122 data elements that include a patient’s full cancer history that can take up to 1 working day to curate. We collaborated with the Realyze Intelligence Healthcare Solutions vendor to use their AI pipeline to generate the manual curated dataset. Realyze generated the CCDE data elements such as histology, pathology site, MMR, TNM staging, ECOG, and KPS for a pilot lung cancer cohort of 150 patients. We manually validated the generated data for 74 out of 150 patients. Methods:The Realyze platform uses a combination of LLMs, ML algorithms and standard terminologies to create a cancer patient model. These models are flexible enough to address the unique needs and challenges of a pan-cancer oncology model. By using standardized FHIR export, results were delivered to a data lake solution and written into a REDCap database to enable human review. Summary:We manually assessed 74 patients. The NLP gave concordant values for MMR, KPS and TNM staging for 100% of the instances. For MMR these were all null values with false negative (FN) of 100% accuracy. Pathology site had 92.15% accuracy while histology has 97.5% accuracy. Conclusion:Will work on refining pathology site and histology’s ICDO3 list to increase the percentage of accuracy. Once Realyze refines their model for these data elements we will re-run it on a larger cohort of cancer patients and calculate the accuracy. Accuracy Results Clinical data elements 74 patients assessed: Accuracy % ECOG 98.6 KPS 100 T (path) 100 T (clinical) 100 N (path) 100 N (clinical) 100 M (path) 100 M(clinical) 100 MMR 100 Histology (path) 97.5 Path site 92.15 Citation Format: Andrew Niederhausern, Nadia S. Bahadur, Gary Wallace, Gilan E. Saadawi, John Philip. Machine learning and large language model approach to pancancer data elements [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4966.
Abstract 4312: KRAS oncogenic activation in <i>Gramd2</i> + AT1 cells form lung adenocarcinoma with distinct transcriptomic and tumor microenvironment signatures
Authors: Minxiao Yang, Jonathan Castillo, Edgar Gonzalez, Chunli Yan, Evanthia Roussos Torres, Zea Borok, Crystal Marconett
Journal: Cancer Research (2024)

Abstract Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer and presents with a high degree of biological heterogeneity and distinct clinical outcomes. The current paradigm of LUAD etiology recognizes alveolar epithelial type II (AT2) cells as the primary cell of origin, while the role of AT1 cells in LUAD oncogenesis remains relatively unknown. Here, we examined transformation via activation of the oncogenic KRASG12D mutation in a Gram-domain containing 2 (Gramd2)+ AT1 cell lineage tracing model system, which resulted in multifocal LUAD, primarily of papillary histology. Spatial transcriptomic sequencing revealed significant differences of transcriptomic signatures and signaling activities between Gramd2+ AT1 cell-derived and Sftpc+ AT2 cell-derived LUAD. Single-cell RNA sequencing of macrodissected LUAD lesions demonstrated heterogeneous cell composition of the tumor microenvironment (TME), with Gramd2+ AT1 cell-derived LUAD fostering a proinflammatory, immunoreactive TME and Sftpc+ AT2-derived LUAD presenting with an immunosuppressive TME. Collectively, our study suggests that cell of origin for LUAD is associated with histologic subtype, transcriptomic aberrations, and immune cell composition within LUAD that may influence response to therapy. Citation Format: Minxiao Yang, Jonathan Castillo, Edgar Gonzalez, Chunli Yan, Evanthia Roussos Torres, Zea Borok, Crystal Marconett. KRAS oncogenic activation in Gramd2 + AT1 cells form lung adenocarcinoma with distinct transcriptomic and tumor microenvironment signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4312.
Abstract 7653: Role of ITGB2 in patients with luminal B1 breast cancer
Authors: Chun-Yu Liu, Ji-Lin Chen, Yi-Fang Tsai, Ta-Chung Chao, Wan-Lun Wang, Pei-Ju Lien, Chih-Yi Hsu, Jiun-I Lai, Chi-Cheng Huang, Jen-Hwey Chiu, Ling-Ming Tseng
Journal: Cancer Research (2024)

Abstract Purpose: Luminal-type breast cancers are the most commonly diagnosed in women. Among them, the luminal B1 subtype exhibits higher proliferation rates and a worse prognosis compared to the luminal A subtype. Despite significant advancements in detection and therapies, recurrence still occurs after primary treatment. In this study, our aim is to identify genomic alterations in early recurrent luminal B1 breast cancer. Experimental Design: In this VGHTPE cohort, we recruited a total of 42 patients diagnosed with stage I-III luminal B1 breast cancer, comprising 15 subjects who experienced recurrence within five years and 27 subjects who did not. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples and subjected to targeted next-generation sequencing. We assessed cell aggressiveness through in vitro transwell migration, invasion, and sphere assays. Results: Luminal B1 breast cancer patients with advanced stage and poorly differentiated tumors were associated with recurrence within five years. Driver gene mutation analysis revealed that TP53 mutations were present in 46.7% of patients who experienced recurrence within five years, compared to 29.6% in the non-recurrence group. In the analysis of copy number variations, the most common amplifications/gains observed in luminal B1 breast cancer patients were in MCL1, MYC, and KLF6. Remarkably, patients who experienced recurrence within five years showed a higher occurrence of gain in ITGB2, the gene encoding the integrin β chain, compared to those who remained recurrence-free. Patients with ITGB2 amplifications/gains had a shorter 5-year recurrence-free survival compared to those with a neutral status. In vitro studies revealed that the knockdown of ITGB2 suppressed cell migration, invasion, and sphere formation in estrogen receptor-positive HER2-negative breast cancer cells. Conclusion: Our study has identified ITGB2 amplifications/gains as a potential biomarker for early recurrence in luminal B1 breast cancer. Citation Format: Chun-Yu Liu, Ji-Lin Chen, Yi-Fang Tsai, Ta-Chung Chao, Wan-Lun Wang, Pei-Ju Lien, Chih-Yi Hsu, Jiun-I Lai, Chi-Cheng Huang, Jen-Hwey Chiu, Ling-Ming Tseng. Role of ITGB2 in patients with luminal B1 breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7653.
Abstract 7624: DNA checkpoint gene mutation as a biomarker of immune checkpoint inhibitor in advanced biliary tract cancer
Authors: Ji Eun Shin, Seung Tae Kim, Dae-Ho Choi, Junho Lee, Jiyeon Hyeon
Journal: Cancer Research (2024)

Abstract Introduction: The DNA checkpoint (DNACHK) pathway is engaged in signaling the need for cell cycle arrest. The G1 and S phase checkpoint allows for repair of damaged DNA, preventing damaged DNA from being copied. The G2 and M phase checkpoint prevents transmission of mutated DNA to the next generation. This pathway, along with mismatch repair (MMR), homologous recombination (HR), and base excision repair (BER), is being actively researched to assess its role in cancer immunotherapy. Methods: Sixty-two patients participated in this study. These patients were treated with immune checkpoint inhibitors (ICIs) for advanced biliary tract cancers (BTCs) from Mar. 2020 to Aug. 2022 at Samsung Medical Center. DNACHK mutations were defined as genomic alterations such as SNVs, MNVs, and short insertion and deletions in seven genes These genes include checkpoint kinase 1 (CHEK1), checkpoint kinase 2 (CHEK2), BRCA1, DNA repair associated (BRCA1), the serine/threonine kinase ATM, the serine/threonine kinase ATR, and mediator of DNA damage checkpoint 1 (MDC1). We analyzed the effect of DNACHK mutations on the efficacy of ICIs in advanced BTCs. Results: Patient median age at diagnosis was 68.0 years. Ten patients (16.1%) had gall bladder (GB) cancer; the remaining patients (n = 52, 83.9%) were diagnosed with cholangiocarcinoma. Among the 62 patients with advanced BTCs treated with ICIs, 37 (59.7%) were categorized into the DNACHK wild-type (WT) group and 25 (40.3%) into the DNACHK mutated (MT) group. The most observed DNA checkpoint mutations were ATM mutations (n=14). MDC1 mutations were found in seven patients, ATR mutations in three, BRCA1 mutations in four, and CHEK2 mutations in three. Patients in the DNACHK MT group had better disease control rates than patients in the DNACHK WT group (60.0% vs. 48.6%, p=0.53). Median overall survival (OS) was 8.1 months (95% CI, 5.1, 22.8) in the MT group and 5.6 months (95% CI, 3.1, 11.0) in the WT group (p=0.33). Conclusions: The results of this study suggest that the DNACHK pathway may be a valuable source of biomarkers for ICI and worthy of further study. Citation Format: Ji Eun Shin, Seung Tae Kim, Dae-Ho Choi, Junho Lee, Jiyeon Hyeon. DNA checkpoint gene mutation as a biomarker of immune checkpoint inhibitor in advanced biliary tract cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7624.