Article
Cell Biology
Jieyun Zhang, Fatao Liu, Yanan Yang, Nuoya Yu, Xiaoling Weng, Yue Yang, Zhe Gong, Shenglin Huang, Lu Gan, Sijie Sun, Xiaowei Zhang, Yiwei Gong, Yun Liu, Weijian Guo
Summary: Gastric cancer can be distinguished at the genetic level based on its metastatic potential, and we have identified potential driver mutations that promote metastasis. These mutations can facilitate metastasis by establishing an immunosuppressive microenvironment. This study provides possibilities for future targeted therapy of gastric cancer.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Jiani Yi, Mengting Wu, Zhihong Zheng, Qing Zhou, Xufan Li, Yan Lu, Pengyuan Liu
Summary: This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis. Distinct DNA methylation and gene expression patterns were found between low-metastasis and high-metastasis cell sublines. Integrated analysis identified 33 methylation-induced genes potentially involved in ovarian cancer metastasis. Epigenetic silencing of SFRP1 and LIPG was found to be a potential driver event in ovarian cancer metastasis.
JOURNAL OF GYNECOLOGIC ONCOLOGY
(2023)
Article
Biology
Yiyan Zhai, Jingyuan Zhang, Zhihong Huang, Rui Shi, Fengying Guo, Fanqin Zhang, Meilin Chen, Yifei Gao, Xiaoyu Tao, Zhengsen Jin, Siyu Guo, Yifan Lin, Peizhi Ye, Jiarui Wu
Summary: This study established a single-cell transcriptional atlas of gastric cancer (GC) and identified prognostic gene signatures associated with T-cells. By analyzing cell-cell communication, trajectory, and transcription factor regulatory network, we predicted the prognosis of GC patients and classified them into high-risk or low-risk groups based on immune-related gene expression.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Oncology
Youli Xia, Xiaping He, Lorna Renshaw, Carlos Martinez-Perez, Charlene Kay, Mark Gray, James Meehan, Joel S. Parker, Charles M. Perou, Lisa A. Carey, J. Michael Dixon, Arran Turnbull
Summary: This study identified molecular mechanisms underlying endocrine therapy resistance (ETR) in hormone receptor-positive breast cancer through in-depth genomic analysis. The results showed that ETR involves diverse changes in somatic genetic and transcriptomic profiles, including mutations, gene expression changes, and activation of signaling pathways. Overcoming resistance will require an individualized approach utilizing genomic and genetic biomarkers and drugs tailored to each patient.
CLINICAL CANCER RESEARCH
(2022)
Review
Oncology
Xueqi Yan, Yinghong Xie, Fan Yang, Yijia Hua, Tianyu Zeng, Chunxiao Sun, Mengzhu Yang, Xiang Huang, Hao Wu, Ziyi Fu, Wei Li, Shiping Jiao, Yongmei Yin
Summary: Breast cancer is a heterogeneous disease with a complex microenvironment involving tumor cells, immune cells, fibroblasts, and vascular cells. Recent advances in single-cell technologies have provided new insights into the diversity of tumor-infiltrating cells in breast cancer. Understanding the phenotypic and functional diversity of intra-tumoral cells is crucial for predicting prognosis and developing effective treatments for breast cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Lindsay Angus, Marcel Smid, Saskia M. Wilting, Manouk K. Bos, Neeltje Steeghs, Inge R. H. M. Konings, Vivianne C. G. Tjan-Heijnen, Johanna M. G. H. van Riel, Agnes J. van de Wouw, Edwin Cuppen, Martijn P. Lolkema, Agnes Jager, Stefan Sleijfer, John W. M. Martens
Summary: This study investigated the mutated genes and mutation patterns, as well as the expression levels of relevant genes, in 101 breast cancer metastatic lesions with ER-positive tumors. The analyses revealed two distinct patient groups, one showing ongoing, active ER and its associated signal route, and the other showing lower ER expression levels. The study highlights the importance of combining mutation and expression analyses to identify patients who may still benefit from anti-hormonal treatment targeting ER.
Article
Urology & Nephrology
J. Alberto Nakauma-Gonzalez, Maud Rijnders, Job van Riet, Michiel S. van der Heijden, Jens Voortman, Edwin Cuppen, Niven Mehra, Sandra van Wilpe, Sjoukje F. Oosting, L. Lucia Rijstenberg, Hans M. Westgeest, Ellen C. Zwarthoff, Ronald de Wit, Astrid A. M. van der Veldt, Harmen J. G. van de Werken, Martijn P. J. Lolkema, Joost L. Boormans
Summary: This study analyzed the molecular and genetic features of metastatic urothelial carcinoma (mUC) and identified different genomic and transcriptomic subtypes, providing potential therapeutic options for individualized treatment. The findings have significant clinical implications.
Article
Oncology
Zi-An Xia, You Zhou, Jun Li, Jiang He
Summary: This study identified five tissue-resident macrophage clusters with a mixed phenotype of M1-M2 macrophages through single-cell RNA sequencing analysis. The comprehensive analysis of multi-omics data revealed that these RTM clusters exhibited an elevated inflammatory response and reactive oxygen species pathway, and were positively correlated with T cell cytotoxicity and infiltration of CD8+ T cells, indicating their potential as predictive biomarkers for immune checkpoint therapy outcomes in breast cancer patients.
Article
Genetics & Heredity
Zachary T. Weber, Katharine A. Collier, David Tallman, Juliet Forman, Sachet Shukla, Sarah Asad, Justin Rhoades, Samuel Freeman, Heather A. Parsons, Nicole O. Williams, Romualdo Barroso-Sousa, Elizabeth H. Stover, Haider Mahdi, Carrie Cibulskis, Niall J. Lennon, Gavin Ha, Viktor A. Adalsteinsson, Sara M. Tolaney, Daniel G. Stover
Summary: This study analyzed high-frequency ctDNA sample series from metastatic triple-negative breast cancer patients, revealing diverse tumor clonal dynamics and genomic features. Despite technical challenges, monitoring ctDNA in metastatic cancers can aid in understanding response and progression, while minimizing patient risk and discomfort.
Article
Immunology
Xiaoxue Zi, Yang Peng, Yiran Zang, Shiying Chen, Mengshi Li, Kena Yu, Xu Liang, Peng Jin, Deyun Wang, Li Shi
Summary: By analyzing the tissue samples of patients with ACPs and healthy controls, we identified the differentially expressed genes and cilia-related genes in ACPs, as well as the morphological changes in ciliated cells. These findings provide new insights into the understanding of the pathogenesis of ACPs.
JOURNAL OF INFLAMMATION RESEARCH
(2023)
Article
Genetics & Heredity
Jie Tang, Kailing Tu, Keying Lu, Jiaxun Zhang, Kai Luo, Haoxuan Jin, Lei Wang, Lie Yang, Weiran Xiao, Qilin Zhang, Xiaoling Liu, Xin Yi Ge, Guibo Li, Zongguang Zhou, Dan Xie
Summary: In this study, despite low genomic divergence between primary and metastatic cancers in bulk data, single-cell whole-exome sequencing data revealed rare mutations and defined two separate cell populations, indicating diverse evolutionary trajectories between primary and metastatic tumor cells. Additionally, 24 metastatic cell-specific mutated genes were identified and their functions in cell migration capacity were validated.
Article
Oncology
Noortje Verschoor, Marcel Smid, Agnes Jager, Stefan Sleijfer, Saskia M. Wilting, John W. M. Martens
Summary: In this study, the researchers investigated the characteristics and therapy resistance of HER2-positive breast cancer through integrating genomics and transcriptomics data. They found that the genomic profiles of primary and metastatic HER2-positive breast cancers were similar, and certain genomic features were predictive of progression-free survival on post-biopsy anti-HER2 treatment. Additionally, a HER2-driven expression profile grouped different types of HER2-positive tumors and indicated the possibility of transformation to ER independence. Integrated genomic and transcriptomic analyses may play a key role in establishing therapeutic options.
BREAST CANCER RESEARCH
(2023)
Article
Cell Biology
Xiaojie Wang, Liang Wang, Mingyi Luo, Qian Bu, Chunqi Liu, Linhong Jiang, Rui Xu, Shaomin Wang, Haoluo Zhang, Jiamei Zhang, Xuemei Wan, Hongchun Li, Yonghai Wang, Bin Liu, Ying Zhao, Yuanyuan Chen, Yanping Dai, Min Li, Hongbo Wang, Jingwei Tian, Yinglan Zhao, Xiaobo Cen
Summary: Clarithromycin (CLA) treatment causes anxiety-like behaviors, possibly through altered glycerophospholipid metabolism.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Oncology
Say Li Kong, Xingliang Liu, Swee Jin Tan, Joyce A. Tai, Ler Yee Phua, Huay Mei Poh, Trifanny Yeo, Yong Wei Chua, Yu Xuan Haw, Wen Huan Ling, Raymond Chee Hui Ng, Tira J. Tan, Kiley Wei Jen Loh, Daniel Shao-Weng Tan, Quan Sing Ng, Mei Kim Ang, Chee Keong Toh, Yi Fang Lee, Chwee Teck Lim, Tony Kiat Hon Lim, Axel M. Hillmer, Yoon Sim Yap, Wan-Teck Lim
Summary: This study conducted concurrent analysis of CTCs and ctDNA using the DropCell platform, revealing the heterogeneity of metastatic tumor in circulation and the progressive genomic changes that may guide the selection of appropriate therapy against evolving tumor clonality. The findings emphasized the impact of the metastatic phenotype and correlated alterations detected in circulation with worse survival outcome for both lung and breast cancer patients. Notably, evolving genetic signatures were detected in CTCs and ctDNA samples during the course of treatment and disease progression.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yi-Ming Liu, Jing-Yu Ge, Yu-Fei Chen, Tong Liu, Lie Chen, Cui-Cui Liu, Ding Ma, Yi-Yu Chen, Yu-Wen Cai, Ying-Ying Xu, Zhi-Ming Shao, Ke-Da Yu
Summary: This study investigates the dynamic changes during the evolution of dissemination in breast cancer by using single-cell RNA sequencing and spatial transcriptomics. It identifies a distinct cell cluster with high levels of oxidative phosphorylation and reveals a switch between glycolysis and oxidative phosphorylation as an early event during lymph node metastasis in breast cancer cells.
Article
Oncology
Amber N. Hurson, Mustapha Abubakar, Alina M. Hamilton, Kathleen Conway, Katherine A. Hoadley, Michael Love, Andrew F. Olshan, Charles M. Perou, Montserrat Garcia-Closas, Melissa A. Troester
Summary: This study identified breast cancer risk factors associated with RNA-based TP53 and ER, providing a new etiologic schema of interest in breast cancer prevention research.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Achal Patel, Montserrat Garcia-Closas, Andrew F. Olshan, Charles M. Perou, Melissa A. Troester, Michael Love, Arjun Bhattacharya
Summary: This study identifies race-specific genetic associations with breast cancer risk of recurrence scores and suggests mediation of these associations by PAM50 subtype and expression, with implications for clinical interpretation of these scores.
Article
Oncology
Jonathan H. Shepherd, Karla Ballman, Mei-Yin C. Polley, Jordan D. Campbell, Cheng Fan, Sara Selitsky, Aranzazu Fernandez-Martinez, Joel S. Parker, Katherine A. Hoadley, Zhiyuan Hu, Yan Li, Matthew G. Soloway, Patricia A. Spears, Baljit Singh, Sara M. Tolaney, George Somlo, Elisa R. Port, Cynthia Ma, Charles Kuzma, Eleftherios Mamounas, Mehra Golshan, Jennifer R. Bellon, Deborah Collyar, Olwen M. Hahn, Clifford A. Hudis, Eric P. Winer, Ann Partridge, Terry Hyslop, Lisa A. Carey, Charles M. Perou, William M. Sikov
Summary: The long-term outcomes of the CALGB 40603 trial showed that adding carboplatin or bevacizumab did not significantly improve the overall survival of patients with stage II-III triple-negative breast cancer. However, patients who achieved a pathological complete response had better long-term outcomes, and immune activation markers were associated with treatment response and improved survival.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Carey K. Anders, Mark G. Woodcock, Amanda E. D. Van Swearingen, Dominic T. Moore, Maria J. Sambade, Sonia Laurie, Alexander Robeson, Oleg Kolupaev, Luz A. Cuaboy, Amy L. Garrett, Karen McKinnon, Kristen Cowens, Dante Bortone, Benjamin C. Calhoun, Alec D. Wilkinson, Lisa Carey, Trevor Jolly, Hyman Muss, Katherine Reeder-Hayes, Rebecca Kaltman, Rachel Jankowitz, Vinay Gudena, Oludamilola Olajide, Charles Perou, E. Claire Dees, Benjamin G. Vincent, Jonathan S. Serody
Summary: This study evaluated the efficacy of using a low dose of cyclophosphamide (Cy) to deplete regulatory T cells (T-regs) before initiating pembrolizumab in patients with triple negative breast cancer (TNBC). The results showed that Cy did not significantly decrease T-regs before pembrolizumab and there was a rapid recovery in T-regs after the first cycle of therapy. Baseline samples with increased B cell gene expression were associated with clinical response and immune-related toxicity (IRT).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Alina M. Hamilton, Amber N. Hurson, Linnea T. Olsson, Andrea Walens, Joseph Nsonwu-Farley, Erin L. Kirk, Yara Abdou, Stephanie M. Downs-Canner, Jonathan S. Serody, Charles M. Perou, Benjamin C. Calhoun, Melissa A. Troester, Katherine A. Hoadley
Summary: The immune microenvironment in breast cancer is closely related to race, age, tumor subtype, and grade. Black and young women have higher immune response, which may be associated with higher recurrence risk.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Medicine, Research & Experimental
Sm N. Udden, Qian Wang, Sunil Kumar, Venkat S. Malladi, Shwu-Yuan Wu, Shuguang Wei, Bruce A. Posner, Sophie Geboers, Noelle S. Williams, Yulun Liu, Jayesh K. Sharma, Ram S. Mani, Srinivas Malladi, Karla Parra, Mia Hofstad, Ganesh Raj, Jose M. Larios, Reshma Jagsi, Max S. Wicha, Ben Ho Park, Gaorav P. Gupta, Arul M. Chinnaiyan, Cheng-Ming Chiang, Prasanna G. Alluri
Summary: High-throughput screening of FDA-approved drugs identified BET inhibitor OTX015 as a top suppressor of ESR1 mutant cell growth, showing superior efficacy compared to fulvestrant. When combined with CDK4/6 inhibitor abemaciclib, OTX015 induced more potent tumor regression than current standard-of-care treatment.
Article
Medicine, General & Internal
Alicia Gunning, Sunil Kumar, Cassin Kimmel Williams, Barry M. Berger, Stephen P. Naber, Piyush B. Gupta, Catherine Del Vecchio Fitz, Charlotte Kuperwasser
Summary: The NavDx blood test is a reliable method for detecting and monitoring HPV-driven cancers by analyzing tumor tissue modified viral-HPV DNA. It has been clinically validated and integrated into clinical practice by over 1000 healthcare providers at over 400 medical sites in the US. The test is accredited by the College of American Pathologists and the New York State Department of Health and has demonstrated high sensitivity and specificity.
Article
Oncology
Frederick M. Howard, James Dolezal, Sara Kochanny, Galina Khramtsova, Jasmine Vickery, Andrew Srisuwananukorn, Anna Woodard, Nan Chen, Rita Nanda, Charles M. Perou, Olufunmilayo I. Olopade, Dezheng Huo, Alexander T. Pearson
Summary: Gene expression-based recurrence assays are recommended for guiding chemotherapy in hormone receptor-positive, HER2-negative breast cancer, but their high cost and limited availability pose challenges. This study presents a deep learning model that utilizes digital histology and clinical risk factors to predict recurrence assay results and the risk of recurrence, surpassing the performance of established clinical nomograms. The model can identify patients with excellent prognoses who may not require further genomic testing.
Article
Oncology
Holly Tovey, Orsolya Sipos, Joel S. Parker, Katherine A. Hoadley, Jelmar Quist, Sarah Kernaghan, Lucy Kilburn, Roberto Salgado, Sherene Loi, Richard D. Kennedy, Ioannis Roxanis, Patrycja Gazinska, Sarah E. Pinder, Judith Bliss, Charles M. Perou, Syed Haider, Anita Grigoriadis, Andrew Tutt, Maggie Chon U. Cheang
Summary: This study explored the predictive ability of DNA damage response (DDR) and immune markers in the treatment response of triple-negative breast cancer. High immune features predict response to docetaxel, while high DDR signature scores predict response to carboplatin. Patients can be divided into different subgroups based on their treatment sensitivity. Caution is needed when using transcriptional signatures derived from primary tumors to guide treatment.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Marni B. McClure, Yasunori Kogure, Naser Ansari-Pour, Yuki Saito, Hann-Hsiang Chao, Jonathan Shepherd, Mariko Tabata, Olufunmilayo I. Olopade, David C. Wedge, Katherine A. Hoadley, Charles M. Perou, Keisuke Kataoka
Summary: Hallmark signatures based on gene expression capture core cancer processes and have significant relationships with genetic alterations. TP53 mutation leads to diverse changes, including increased proliferation and glycolysis, similar to widespread copy-number alterations. Basal-like breast and bladder cancers demonstrate specific genetic and phenotypic changes related to squamous tumors, indicating potential therapeutic options across tumor types. These findings highlight the heterogeneity of hallmark signatures and suggest an oncogenic program induced by TP53 mutation and selected aneuploidy events.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Alina M. Hamilton, Sarah C. Van Alsten, Xiaohua Gao, Joseph Nsonwu-Farley, Benjamin C. Calhoun, Michael I. Love, Melissa A. Troester, Katherine A. Hoadley
Summary: Markers of genomic instability, including TP53 status and HRD, are candidate biomarkers of immunogenicity and immune-mediated survival in breast cancer. This study used RNA expression to investigate the association between genomic instability and the breast cancer immune microenvironment. The results showed that genomic instability signatures were associated with immune expression and improved recurrence-free survival, highlighting the potential of genomic instability as a marker for predicting immunotherapy response.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Yifeng Shi, Linnea T. Olsson, Katherine A. Hoadley, Benjamin C. Calhoun, J. S. Marron, Joseph Geradts, Marc Niethammer, Melissa A. Troester
Summary: Approaches for rapidly identifying patients at high risk of early breast cancer recurrence are needed. Image-based methods for prescreening tumor slides stained with hematoxylin and eosin (H&E) could provide temporal and financial efficiency. Deep learning was leveraged to extract image information and train a model to identify recurrence. Our image model identified 70% of early-recurrent low-intermediate grade tumors, providing complementary information for predicting early recurrence compared to existing markers.
Article
Oncology
Ryan M. Murphy, Jason Tasoulas, Alessandro Porrello, Miranda B. Carper, Yi-Hsuan Tsai, Alisha R. Coffey, Sunil Kumar, Peter YF. Zeng, Travis P. Schrank, Bentley R. Midkiff, Stephanie Cohen, Ashley H. Salazar, Michele C. Hayward, D. Neil Hayes, Andrew Olshan, Gaorav P. Gupta, Anthony C. Nichols, Wendell G. Yarbrough, Chad V. Pecot, Antonio L. Amelio
Summary: Over 70% of oropharyngeal head and neck squamous cell carcinoma (HNSC) cases in the United States are positive for human papillomavirus (HPV). This study identified robust expression of Synaptogyrin-3 (SYNGR3) gene in immune cells of HPV(+) squamous cancers and demonstrated that codetection of SYNGR3 and p16 by immunohistochemistry (IHC) can more reliably identify the low-risk subgroup of patients that may be appropriate for deescalation treatments.
CANCER RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Danielle J. Fassler, Luke A. Torre-Healy, Rajarsi Gupta, Alina M. Hamilton, Soma Kobayashi, Sarah C. Van Alsten, Yuwei Zhang, Tahsin Kurc, Richard A. Moffitt, Melissa A. Troester, Katherine A. Hoadley, Joel Saltz
Summary: This study evaluated the role of tumor-infiltrating lymphocytes (TILs) in breast cancer and assessed their significance as biomarkers using computational pathology. The findings suggest that the abundance and spatial distribution of TILs are associated with clinical prognosis, and are important for predicting the risk of recurrence.