tbuckley/cabot-search huggingface dataset:
Abstract 7640: Prognostic significance of S100A16 expression in patients with resected lung adenocarcinoma
Authors: Jung-Jyh Hung
Journal: Cancer Research (2024)

Abstract Background: Lung cancer is the leading cause of cancer death worldwide. Tumor recurrence is the most common cause of treatment failure after surgical resection. The S100 protein family is a multigenic group of cytoplasmic calcium-binding proteins. S100A16 has to be reported to be an independent prognostic indicator of poor overall survival in lung adenocarcinoma recently. However, the prognostic value of S100A16 in recurrence-free survival (RFS) in patients with resected lung adenocarcinoma has not been well demonstrated. The relationship between S100A16 expression and the histological subtypes of lung adenocarcinoma remained unknown. Methods: A total of 79 patients with resected lung adenocarcinoma were included in the study. S100A16 expression was determined by immunohistochemistry in tumor specimens. The prognostic value of S100A16 overexpression and its relationship with clinicopathological variables, including histology subtypes, were investigated. Results: S100A16 overexpression tended to be significantly associated with order age (P = 0.074). There was no significant association between S100A16 overexpression and predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (P = 0.447). Univariate analysis indicated that pathologic stage (II or III vs. I) (P = 0.001) and S100A16 overexpression (P = 0.005) were significant prognostic factors for worse recurrence-free survival (RFS). Predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (P = 0.064) tended to be a significant prognostic factor for worse RFS. In multivariate analysis, pathologic stage (II or III vs. I) (HR, 27.847; 95% CI, 4.173 to 185.831; P = 0.001), and S100A16 overexpression (HR, 21.740; 95% CI, 2.516 to 187.870; P = 0.005) were still significant prognostic factors for worse RFS. Conclusions: S100A16 overexpression was a significant prognostic factor for worse RFS in patients with resected lung adenocarcinoma. This information is useful to stratify high-risk patients of recurrence after resection of lung adenocarcinoma. Citation Format: Jung-Jyh Hung. Prognostic significance of S100A16 expression in patients with resected lung adenocarcinoma [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 7640.
Abstract 2980: Exploiting the selenoproteome in uveal melanoma
Authors: Alyssa Sanders, Camille Cunanan, Edward Hartsough
Journal: Cancer Research (2024)

Abstract Uveal melanoma (UM) is a common intraocular malignancy arising from GNAQ/GNA11 mutations in uveal tract melanocytes. Although primary UM is treatable by radiation and enucleation, half of patients will develop liver metastasis. Unfortunately, patients with metastatic UM have a poor prognosis of approximately one-year - underscoring metastatic UM as one of the deadliest cancers. A strong prognostic indicator for UM liver metastases is a deletion or inactivation of the deubiquitinase BAP1, yet its specific role in disease progression is unclear. Intriguingly, upon BAP1 loss of function, the cysteine importer SLC7A11 is up regulated. Imported cysteine can be converted into glutathione serving as a cofactor for antioxidant enzymes like GPX4, a selenoprotein (SeP). SePs are a protein family characterized by having at least one selenocysteine - a selenium (Se) containing amino acid. Interestingly, the liver serves as a major hub for Se transport via Selenoprotein P (SEPP). The selenocysteine rich SEPP is secreted by hepatocytes and catabolized in recipient cells facilitating synthesis of de novo SeP. Here we hypothesize that mutant BAP1 UM utilizes the liver’s Se rich microenvironment to augment selenoproteome expression to stave off oxidative stress. Using publicly available datasets, we found patients with mutant BAP1 UM have increased expression of antioxidants proteins and genes associated with SeP expression. In a panel of BAP1 expressing and deficient UM cells, we found that BAP1 deficient cells have increased expression of SePs, suggesting a predisposition to resist oxidative stress. In the presence of exogenous Se, UM cell lines upregulate SeP expression indicating the importance of selenium availability for SeP expression. In addition, a hepatocyte cell line, and an ex vivo liver slice co-culture model was used to confirm that SEPP was produced in the liver slices and was associated with increased SeP expression in UM cells. Furthermore, we found that BAP1 null UM cells were more susceptible to GPX4 inhibition compared to wild type cells, suggesting a reliance on SeP expression. Taken together, these findings suggest that the liver associated selenoproteome expression may underpin an oxidative stress-associated therapeutic vulnerability in UM liver metastases. Citation Format: Alyssa Sanders, Camille Cunanan, Edward Hartsough. Exploiting the selenoproteome in uveal melanoma [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 2980.
Abstract 6476: Solving the real-world data challenge: A hybrid resourcing model to curate RWD at scale
Authors: Julia Rudolph, Kenneth L. Kehl, Melanie Bernstein
Journal: Cancer Research (2024)

Abstract Introduction: As cancer treatments become more complex, the need for structured real-world data (RWD) to support clinical research is critical. However, researchers often lack resources to curate data in-house. Organizations are challenged with timely data curation at the quality and scale needed for real world applications. Methods: As members of the AACR Project GENIE (Genomics Evidence Neoplasia Information Exchange) Biopharma Collaborative (BPC), Memorial Sloan Kettering Cancer Center (MSK) and Dana-Farber Cancer Institute (DFCI) partnered with Vasta Global, an Omega Healthcare company, to build a model for curating RWD at scale, allowing for cost-effective RWD curation while leveraging expert resources and best practices. The approach includes managing a hybrid onshore and offshore team with clear communication and recurring check-ins, cross-training curators on different EHRs to reallocate Vasta Global resources and maintain project pace, building program-specific clinical data curation training, establishing QA and delivery methods, standardizing data curation, assigning productivity standards, aligning data quality practices and benchmarks, and developing data visualizations and analytics to show progress and insights. Results: In Phase 1 of the AACR GENIE BPC, data was curated from four sites: MSK, DFCI, Vanderbilt Ingram Cancer Center (VICC) in Nashville, and Princess Margaret Cancer Centre, University Health Network (UHN) in Toronto. During Phase 1, MSK and DFCI, with Vasta Global’s assistance, delivered high-quality RWD for 6,475 patients (NSCLC = 1,591; CRC = 1,264; Bladder = 639; Breast = 957; Pancreas 989; and Prostate = 1,035). All data for these cohorts will be publicly available by Spring 2024 in the AACR Project GENIE cBioPortal. MSK and DFCI generated usable and fit-for-purpose RWD to help advance oncology clinical decision-making and data sharing. Conclusion: Accelerating RWD curation will empower the oncology community to leverage data-driven insights and advance treatment opportunities for cancer patients. Working alongside lead sites, a partner like Vasta Global enables researchers to leverage extensive expertise in the BPC data model, allowing for consistency and scalability of the BPC program. In this hybrid model, research partners can curate RWD in a cost-effective way, while remaining focused on core research responsibilities. Citation Format: Julia Rudolph, Kenneth L. Kehl, Melanie Bernstein. Solving the real-world data challenge: A hybrid resourcing model to curate RWD at scale [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 6476.
Abstract 430: Precision diet and lipid modulating agents to induce lipid oxidation in breast cancer
Authors: Mahsa Yavari, Jordan Torpey, Marie Sabatier, Alanis Carmona, Krystina Szylo, Midori Flores, Mario Palma, Cameron Fraser, Yanshan Liang, Sheng Tony Hui, Oana Zeleznik, Heather Eliassen, Jessalyn Ubellacker
Journal: Cancer Research (2024)

Abstract Metastasis is the primary cause of breast cancer-related mortality, and understanding the intricate relationship between the tumor microenvironment, lipid metabolism, and metastasis is crucial for preventing cancer progression. Previous work from our group demonstrated that high exogenous levels of oleic acid, a monounsaturated fatty acid (MUFA), in the lymph node environment protects melanoma cells from ferroptosis. Ferroptosis is an iron-dependent form of cell death induced by accumulation of lipid peroxides, which are commonly formed from polyunsaturated fatty acids (PUFAs), but not MUFAs. Here, we hypothesized that increasing dietary PUFAs would alter the exogeneous lipid content of the lymph node environment, thus rendering breast cancer cells more sensitive to ferroptosis. To test this, we determined the in vitro sensitivity of 4T1 triple negative breast cancer cells to ferroptosis when treated with various PUFAs and MUFAs. We also assessed the impact of various PUFA and MUFA fatty acid-enriched diets on breast cancer metastasis and ferroptosis resistance in the lymph nodes in vivo. In concordance with previously published work, our results demonstrated that pharmacological induction of ferroptosis in vitro increased lipid oxidation and was mitigated by fatty acid treatments with higher MUFA compared to PUFA content. In vivo, cancer cells in lymph nodes of mice on palm oil diets had lower lipid oxidation compared to cancer cells from tumors in the mammary fat pad. These findings support the hypothesis that dietary lipids can alter ferroptosis response and the extent of lipid oxidation in breast cancer cells within lymph nodes. Our research has the potential to further reveal mechanistic connections between dietary lipids, the lymphatic microenvironment, and breast cancer progression. Citation Format: Mahsa Yavari, Jordan Torpey, Marie Sabatier, Alanis Carmona, Krystina Szylo, Midori Flores, Mario Palma, Cameron Fraser, Yanshan Liang, Sheng Tony Hui, Oana Zeleznik, Heather Eliassen, Jessalyn Ubellacker. Precision diet and lipid modulating agents to induce lipid oxidation in 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 430.
Abstract 7633: CXCR6 positive circulating mucosal-associated invariant T cells play the anti-tumor effect in non-small cell lung caner immunotherapy
Authors: Jingjing Qu, Binggen Wu, Yuekang Li, Qian Shen, Wenjia Sun, Lijun Chen, Jianya Zhou, Jianying Zhou
Journal: Cancer Research (2024)

Abstract Background: Mucosal-associated invariant T (MAIT) cells is are unconventional innate-like T lymphocytes abundant in human tissues. Recent studies have shown that MAIT cells play important roles in regulating tumor immunity. However, the immune characteristics of MAIT cells in non-small cell lung cancer (NSCLC) and its correlation with ICIs treatment efficacy remain unclear. Method: In this study, we used single-cell RNA-sequencing (scRNA-seq), flow cytometry and multiplex immunofluorescence to assess the proportion and characteristics of CD8+MAIT cells in metastatic NSCLC patients who respond or not respond to anti-PD-1 therapy. Results: The proportions of activated and proliferating CD8+ T cells and MAIT cells were significantly higher in responders-derived PBMC or lung tissues prior to anti-PD-1 therapy. Both peripheral and tumor-infiltrating CD8MAIT cells displayed upregulated CXCR6(P&amp;lt;0.05). Besides, CXCR6+CD8MAIT cells from responders had higher expression of cytotoxicity-related genes, like CST7, GNLY, KLRG1, NKG7 and PRF1. Moreover, we found that patients with &amp;gt;1.7% of MAIT among peripheral CD8+ population showed a better response to immunotherapy. Conclusion: CD8MAIT cells may be considered a predictive biomarker for patients responding to anti-PD-1 therapy in NSCLC. The correlation between CD8MAIT and immunotherapy sensitivity may ascribe to high expression of CXCR6. Citation Format: Jingjing Qu, Binggen Wu, Yuekang Li, Qian Shen, Wenjia Sun, Lijun Chen, Jianya Zhou, Jianying Zhou. CXCR6 positive circulating mucosal-associated invariant T cells play the anti-tumor effect in non-small cell lung caner immunotherapy [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 7633.
Abstract 6436: Tumor-educated platelets for therapy stratification of metastasized castration resistant prostate cancer (CRPC)
Authors: Jonas A. Nilsson, Marie Lundholm, Lee-Ann Tjon-Kon-Fat, Linda Köhn, Camilla Thellenberg-Karlsson, Andreas Josefsson, Pernilla Wikström
Journal: Cancer Research (2024)

Abstract One in ten men diagnosed with prostate cancer will have metastases. At some point the metastases becomes castration therapy resistant, contributing leading to the high mortality of prostate cancer. Novel androgen directed treatments, like abiraterone and enzalutamide, have made substantial difference to therapy response, yet only within subgroups of CRPC patients. Correct therapy stratification may prolong the life of the patients, possibly turning a deadly disease into a more chronic disease. For this to happen we need predictive biomarkers that can be used to longitudinally follow the disease in order to identify vulnerabilities and to monitor acquired resistance, e.g. we need to develop personalized liquid biopsy platforms. Using the platelet enriched fraction of a blood sample we here show that we can use the platelets ability to sequester material during circulation to provide information derived from the tumor, a.k.a. tumor-educated platelets. This information could be used as a companion diagnostic to identify patients that will respond to therapy, and to longitudinally monitor tumor progression. In this study, a previously published three gene profile, plt3G profile, was validated in a larger cohort (n=97) and showed that combined analysis of the three genes transcripts (KLK3, FOLH1, NPY) could be used to identify long-term responders regarding progression-free survival after enzalutamide (n=47; PFS; LR p&amp;lt;0,001, HR 0,32, p&amp;lt;0,001) or abiraterone (n=50; PFS; LR p=0.007, HR 0.45, p=0,009) -treatment. Furthermore, progression and resistance development could be accurately longitudinal followed. The plt3G profile showed a significant overlap with circulating tumor DNA (ctDNA) biomarkers, but in addition also provided predictive information around treatment response. Tumor-educated platelets provide therapy-predictive biomarkers as well as biomarkers for longitudinal monitoring of disease progression and resistance development, which ultimately could provide information for therapy switching. Their easy accessibility makes tumor-educated platelets an attractive biosource to be used alone or in combination others, to enable a fluid biomarker platform with the aim to turn a lethal cancer disease into a more chronic disease. Citation Format: Jonas A. Nilsson, Marie Lundholm, Lee-Ann Tjon-Kon-Fat, Linda Köhn, Camilla Thellenberg-Karlsson, Andreas Josefsson, Pernilla Wikström. Tumor-educated platelets for therapy stratification of metastasized castration resistant prostate cancer (CRPC) [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 6436.
Abstract 1753: <i>SHOC2</i> is a genetic dependency in <i>NRAS</i>-mutant melanoma
Authors: Andrea Y. Gu, Tet-Woo Lee, Aziza Khan, Francis W. Hunter, Dean C. Singleton, Stephen M. F. Jamieson
Journal: Cancer Research (2024)

Abstract Melanoma is the most lethal form of skin cancer, with over 300,000 new cases worldwide every year. Specifically, melanoma with NRAS mutations are of particular clinical concern due to their association with a poor prognosis and lack of specific treatment options. Therefore, there is a pressing need for novel approaches to address the treatment of NRAS-mutant melanoma. A current approach to identify novel drug targets is based on the genetic concept of induced essentiality, where functional interactions that occur in response to oncogene addiction create a dependency on another gene. To identify genetic dependencies in NRAS-mutant melanoma, whole-genome CRISPR-Cas9 knockout screens were conducted in 6 NRAS-mutant and 7 NRAS-wild-type (wt) early-passage New Zealand melanoma (NZM) cell lines that were established and maintained at 5% oxygen to mimic physiological oxygen conditions. The NZM cell lines were stably transduced with the whole-genome Brunello lentiviral single guide (sg) RNA library and screened for up to 35 days. BAGEL (Bayesian Analysis of Gene Essentiality) analyses of the NZM whole-genome knockout screens, alongside CRISPR-Cas9 screening data using the Avana sgRNA library from an additional 28 melanoma cell lines, available on the Cancer Cell Line Encyclopaedia (CCLE) database, revealed prospective gene candidates that exhibit greater detrimental effects on the fitness of NRAS-mutant cell lines compared to the NRAS-wt lines. These genes are being further validated as essential genes for NRAS-mutant melanoma cells through custom sgRNA library knockout screens and in vitro individual gene knockout studies. In particular, we demonstrate that knockout of SHOC2, a gene that encodes a scaffold protein essential for activation of the MAPK signalling pathway, results in the prevention of ERK phosphorylation and a more substantial reduction in cell growth in NRAS-mutant NZM cell lines when compared to NRAS-wt lines. These results support previous studies that have identified SHOC2 as a potential therapeutic target for RAS-driven cancers and suggest that targeting of SHOC2 may have utility in NRAS-mutant melanoma, where greater treatment options are urgently needed. Citation Format: Andrea Y. Gu, Tet-Woo Lee, Aziza Khan, Francis W. Hunter, Dean C. Singleton, Stephen M. F. Jamieson. SHOC2 is a genetic dependency in NRAS-mutant melanoma [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 1753.
Abstract 2988: TUG1 exosomal lncRNA sponges let-7 miRNA family members and advances prostate cancer
Authors: Rahaba Makgotso Marima, Mandisa Mbeje, Jeyalakshmi Kandhavelu, Clement Penny, Zodwa Dlamini
Journal: Cancer Research (2024)

Abstract Exosomal long-non coding RNAs (lncRNAs) play an important role in cancer progression and have potential prognostic biomarker potential in several cancers including prostate cancer (PCa). Taurine-upregulated gene 1 (TUG1) is an oncogenic lncRNA overexpressed in PCa. This exosomal lncRNA has been reported to promote PCa migration, invasion and Epithelial-Mesenchymal Transition (EMT). However, TUG1 PCa prognostic mechanisms remain to be elucidated. This study aimed to profile differentially expressed lncRNAs in PCa high-grade tumor cells (PC-3) cells compared to low-grade PCa tumor cells (LNCaP). This was achieved by using a 384-well plate of PCa lncRNA gene panel. A human lncRNA database, LncSEA and other bioinformatics tools were used for annotation and enrichment analysis. RT-qPCR was used to confirm the gene array data. Up or down-regulation of ±2 and p &amp;lt;0.05 were considered significant. Forty two (42%) percent and 14% of lncRNAs were shown to be up and downregulated, respectively. Notably, TUG1 was shown to be upregulated in PC-3 cells from PCR array and RT-qPCR results. Bioinformatics analysis revealed that TUG1 is involved in several cancer hallmarks including apoptosis evasion, migration, invasion and EMT. Furthermore, lncRNA/miRNA complexes regulate a series of oncogenic signaling pathways and this study demonstrated that TUG1 sponges the let-7 miRNA family members (a highly conserved tumor suppressor miRNA family) and promotes PCa progression. Precise mechanisms of TUG1/let-7 axis in PCa prognosis need to be largely elucidated as this may hold potential to understanding lncRNA/miRNA-mediated PCa progression and thus be targeted for novel therapeutics. Citation Format: Rahaba Makgotso Marima, Mandisa Mbeje, Jeyalakshmi Kandhavelu, Clement Penny, Zodwa Dlamini. TUG1 exosomal lncRNA sponges let-7 miRNA family members and advances prostate 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 2988.