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Chen W, Zeng S, Zhong J, Zou J, Lei Y, Chen X, Mei Q, Luo Q. Mapping immune cell dynamics and macrophage plasticity in breast cancer tumor microenvironment through single-cell analysis. Discov Oncol 2025; 16:625. [PMID: 40293603 PMCID: PMC12037460 DOI: 10.1007/s12672-025-02419-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 04/17/2025] [Indexed: 04/30/2025] Open
Abstract
Breast cancer (BRCA) is a complex disease influenced by the tumor microenvironment, where interactions between immune cells and cancer cells play a crucial role in tumor progression and response to therapy. Understanding the intricacies of these interactions requires detailed analysis at the single-cell level, enabling the identification of specific immune cell subpopulations and their functional roles within the tumor milieu. This study comprehensively analyzed immune cell subpopulations and macrophage subtypes in BRCA using single-cell RNA sequencing technology and various computational tools. Initially, Sc-Type software accurately identified and annotated immune cell subpopulations, followed by CNV analysis using infercnv software, revealing significant CNV variations in epithelial cells. Subsequently, macrophages were re-clustered into 5 clusters, and their biological significance and functional features were assessed. CellChat analysis elucidated potential interactions between macrophage subtypes and BRCA cells, primarily through SPP1-CD44 and LGALS9-CD44 signaling networks. Additionally, CytoTRACE and Monocle were employed to analyze cellular plasticity and differentiation trajectories of macrophage subtypes. Furthermore, efferocytosis-related gene set scoring, transcription factor analysis, and risk score development were conducted, followed by immune infiltration and tumor mutation burden analysis, revealing increased immune infiltration and higher TMB levels in the high-risk group. These findings offer crucial insights into the interaction mechanisms of immune cells and macrophage subtypes within the BRCA tumor microenvironment, aiding in the understanding of tumor progression and therapeutic interventions.
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Affiliation(s)
- Wang Chen
- Department of Pharmacy, The Affiliated Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People's Republic of China
| | - Siyu Zeng
- Department of Pharmacy, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, No. 466, Xingangzhong Road, Haizhu District, Guangzhou, 510317, People's Republic of China
| | - Junyong Zhong
- Department of Oncology, Longgang Central Hospital of Shenzhen, Shenzhen, 518116, People's Republic of China
| | - Jian Zou
- Department of Pharmacy, The Affiliated Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People's Republic of China
- School of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Yanli Lei
- Department of Pharmacy, The 2, People's Hospital of Bijie, Bijie, , Guizhou, China
| | - Xiaohan Chen
- Department of Pharmacy, The Affiliated Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People's Republic of China
| | - Qinghua Mei
- Department of Pharmacy, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, No. 466, Xingangzhong Road, Haizhu District, Guangzhou, 510317, People's Republic of China.
| | - Qianhua Luo
- Department of Pharmacy, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, No. 466, Xingangzhong Road, Haizhu District, Guangzhou, 510317, People's Republic of China.
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Alkhaifi M, Zhang E, Peera M, Jerzak K, Czarnota G, Eisen A, Roberts A, Carmona-Gonzalez CA, Pezo R, Gandhi S. Risk Factors for Treatment Toxicity and High Side Effect Burden Among Breast Cancer Survivors: A Retrospective Chart Review. Cancers (Basel) 2025; 17:328. [PMID: 39858109 PMCID: PMC11764302 DOI: 10.3390/cancers17020328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES This study describes the sequelae, side effects, and toxicities experienced by Canadian breast cancer survivors at a breast cancer survivorship clinic at a tertiary academic cancer centre and identifies potential risk factors which may be associated with increased side effect burden. METHODS A retrospective chart review was performed of adult patients treated at the Sunnybrook Breast Cancer Survivorship Clinic from 6 July 2022, to 30 September 2023 (n = 435). RESULTS Most patients (72.6%) reported at least one side effect impacting their quality of life, and a smaller majority (55.4%) reported two or more side effects. The most common symptoms experienced were anxiety (29.4%), chronic pain (23.9%), hot flashes (21.4%), and fear of recurrence (19.8%). Older age was strongly correlated with a lower likelihood of experiencing greater side effect burden (p < 0.01). Patients who underwent chemotherapy were significantly more likely to experience higher side effect burden than patients who did not. Current smokers were more likely than nonsmokers or past smokers to have a higher burden, for both physical (p < 0.01) and psychological side effects (p < 0.01). The multivariate analysis demonstrated that younger age was strongly associated with greater side effect burden, higher likelihood of psychological and physical symptoms, and greater likelihood of requiring close follow-up. CONCLUSIONS The results highlight the need for survivorship resources tailored to survivors under the age of 55 and the importance of referring smokers to smoking cessation programs. Additional research is required to explore the significant reluctance among patients regarding discharge. Future studies should examine the acute needs of younger breast cancer survivors and investigate the impact of smoking and treatment modalities on the side effect burden.
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Affiliation(s)
- Muna Alkhaifi
- Department of Medical Oncology & Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (E.Z.); (K.J.); (A.E.); (S.G.)
| | - Elwyn Zhang
- Department of Medical Oncology & Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (E.Z.); (K.J.); (A.E.); (S.G.)
| | - Malika Peera
- Faculty of Health Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada;
| | - Katarzyna Jerzak
- Department of Medical Oncology & Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (E.Z.); (K.J.); (A.E.); (S.G.)
| | - Gregory Czarnota
- Department of Radiation Oncology Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada;
| | - Andrea Eisen
- Department of Medical Oncology & Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (E.Z.); (K.J.); (A.E.); (S.G.)
| | - Amanda Roberts
- Department of Surgical Oncology Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada;
| | - Carlos Amir Carmona-Gonzalez
- Division of Medical Oncology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada;
| | - Rosanna Pezo
- Department of Biological Sciences, Odette Cancer Research Program, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada;
| | - Sonal Gandhi
- Department of Medical Oncology & Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (E.Z.); (K.J.); (A.E.); (S.G.)
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Chen X, Cao Y, Huang S, Chen Y, Zhang CP. Current status and hotspots in breast cancer patient self-management research: A bibliometric and visual analysis via CiteSpace. Medicine (Baltimore) 2024; 103:e39945. [PMID: 39560549 PMCID: PMC11575949 DOI: 10.1097/md.0000000000039945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 09/13/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND Breast cancer remains a leading cause of cancer-related mortality worldwide. Patient self-management plays a pivotal role in enhancing outcomes and quality of life for individuals affected by this disease. This study employed bibliometric and visual analysis techniques utilizing CiteSpace to elucidate the current status and research hotspots in breast cancer patient self-management from January 1, 2005, to August 31, 2023. METHODS A comprehensive search was conducted in the Web of Science Core Collection (WoSCC). The retrieved literature was subjected to visualization and analysis using CiteSpace, focusing on publication timeline, article count, geographical distribution, institutional affiliations, journal sources, reference co-citation networks, and keyword analysis. RESULTS The analysis encompassed 1413 English-language documents. The United States emerged as the most prolific contributor, while the University of Toronto demonstrated the highest institutional output. The two-map overlay revealed prominent citation paths, indicating strong interconnections between publications in "Medicine, Medicine, Clinical" and "Health, Nursing, Medicine," as well as "Psychology, Education, Health" and "Health, Nursing, Medicine." The most frequently co-cited reference was "Self-Management: Enabling and Empowering Patients Living with Cancer as a Chronic Illness." High-frequency keywords identified included quality of life, chronic disease, self-management, patient education, randomized controlled trials, education, and intervention. These keywords formed 11 distinct clusters related to intervention content, methodologies, outcome indicators, and emerging research trends. Keyword burst analysis predicted future research hotspots focusing on patient needs, psychological distress, Internet technology, and mobile applications. CONCLUSIONS Research in breast cancer self-management is experiencing significant growth. Enhanced collaboration between countries, regions, and institutions is imperative. Further investigation is warranted, particularly in the domains of "quality of life," "patient education," and "mobile health." These findings provide valuable insights to guide future research directions in this critical field.
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Affiliation(s)
- Xinyue Chen
- Nursing School, Xinjiang Medical University, Urumqi, China
| | - Yan Cao
- Nursing School, Xinjiang Medical University, Urumqi, China
- Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, China
| | - Shan Huang
- Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, China
| | - Yanyan Chen
- Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, China
| | - Cui-ping Zhang
- Nursing School, Xinjiang Medical University, Urumqi, China
- Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, China
- Xinjiang Regional Research Center for Population Disease and Health Care, Urumqi, China
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Le Provost B, Parent MÉ, Villeneuve PJ, Waddingham CM, Brook JR, Lavigne E, Dugandzic R, Harris SA. Residential exposure to ambient fine particulate matter (PM 2.5) and nitrogen dioxide (NO 2) and incident breast cancer among young women in Ontario, Canada. Cancer Epidemiol 2024; 92:102606. [PMID: 38986354 DOI: 10.1016/j.canep.2024.102606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 06/10/2024] [Accepted: 06/23/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Air pollution has been classified as a human carcinogen based largely on findings for respiratory cancers. Emerging, but limited, evidence suggests that it increases the risk of breast cancer, particularly among younger women. We characterized associations between residential exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and breast cancer. Analyses were performed using data collected in the Ontario Environmental Health Study (OEHS). METHODS The OEHS, a population-based case-control study, identified incident cases of breast cancer in Ontario, Canada among women aged 18-45 between 2013 and 2015. A total of 465 pathologically confirmed primary breast cancer cases were identified from the Ontario Cancer Registry, while 242 population-based controls were recruited using random-digit dialing. Self-reported questionnaires were used to collect risk factor data and residential histories. Land-use regression and remote-sensing estimates of NO2 and PM2.5, respectively, were assigned to the residential addresses at interview, five years earlier, and at menarche. Logistic regression was used to estimate odds ratios (OR) and their 95 % confidence intervals (CI) in relation to an interquartile range (IQR) increase in air pollution, adjusting for possible confounders. RESULTS PM2.5 and NO2 were positively correlated with each other (r = 0.57). An IQR increase of PM2.5 (1.9 µg/m3) and NO2 (6.6 ppb) at interview residence were associated with higher odds of breast cancer and the adjusted ORs and 95 % CIs were 1.37 (95 % CI = 0.98-1.91) and 2.33 (95 % CI = 1.53-3.53), respectively. An increased odds of breast cancer was observed with an IQR increase in NO2 at residence five years earlier (OR = 2.16, 95 % CI: 1.41-3.31), while no association was observed with PM2.5 (OR = 0.96, 95 % CI 0.64-1.42). CONCLUSIONS Our findings support the hypothesis that exposure to ambient air pollution, especially those from traffic sources (i.e., NO2), increases the risk of breast cancer in young women.
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Affiliation(s)
- Blandine Le Provost
- Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada; Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED), École de Santé Publique, Université de Bordeaux, Bordeaux, France
| | - Marie-Élise Parent
- Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, Université du Québec, Laval, Québec, Canada; Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montreal, Quebec, Canada; Centre de recherche du CHUM, Montréal, Québec, Canada
| | - Paul J Villeneuve
- Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
| | | | - Jeffrey R Brook
- Divisions of Epidemiology and Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Department of Civil and Mineral Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Eric Lavigne
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Population Studies Division, Health Canada, Ottawa, Ontario, Canada
| | - Rose Dugandzic
- Office of Environmental Health, Health Canada, Ottawa, Ontario, Canada
| | - Shelley A Harris
- Divisions of Epidemiology and Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
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Zhang Y, Li J. Recent advancements in understanding of biological role of homeobox C9 in human cancers. World J Clin Oncol 2024; 15:1168-1176. [PMID: 39351453 PMCID: PMC11438841 DOI: 10.5306/wjco.v15.i9.1168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 07/14/2024] [Accepted: 08/02/2024] [Indexed: 08/29/2024] Open
Abstract
Homeobox (HOX) C9, a member of the HOX family, is an important transcription factor, and it plays a significant role in various biological processes. This family of genes is highly valued for their essential roles in establishing and maintaining the body axis during embryonic development and adult tissues. Further, HOXC9 plays a central role in neuronal differentiation, angiogenesis, and adipose distribution, which are essential for the development of the nervous system, maturation of tissues and organs, and maintenance of energy balance and metabolic health. Recent research has found that abnormal HOXC9 expression is closely associated with the development and progression of various tumor types. The HOXC9 expression level can be an indicator of tumor prognosis. Therefore, elucidating the association between HOXC9 expression and its regulatory mechanisms and tumorigenesis can provide novel insights on the diagnosis and treatment of patients with cancer.
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Affiliation(s)
- Yong Zhang
- Department of Clinical Laboratory, The Affiliated Lianyungang Oriental Hospital of Kangda College of Nanjing Medical University, Lianyungang 222042, Jiangsu Province, China
| | - Jing Li
- Department of Respiratory and Critical Care Medicine, The Affiliated Lianyungang Oriental Hospital of Kangda College of Nanjing Medical University, Lianyungang 222042, Jiangsu Province, China
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Szakun N, Liva S, Bodner ME, Wolff A, Kim MY, Cote AT. Prevalence of Sex-Specific Cardiovascular Disease Risk Factors, Medical Risk, and Engagement in Health-Promoting Behaviours in Premenopausal Females. CJC Open 2024; 6:301-313. [PMID: 38487073 PMCID: PMC10935687 DOI: 10.1016/j.cjco.2023.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 11/04/2023] [Indexed: 03/17/2024] Open
Abstract
Background Several sex-specific risk factors (SS-RFs) increase a women's risk for cardiovascular disease (CVD) but are often overlooked during risk assessment. The purpose of this study was to identify the prevalence of SS-RFs and assess CVD risk, knowledge, perceptions and behaviours in premenopausal Canadian women. Methods An online survey was distributed across Canada to premenopausal biological females (19-49 years of age). The survey gathered demographics, medical history, engagement in health-promoting behaviours, and knowledge and perceptions of CVD risk. CVD risk was calculated using medical risk and SS-RFs were tabulated from medical history. Results A total of 2559 participants (33 ± 8 years) completed the survey. The majority of our sample (82%) was classified as low medical risk. Of those classified as low risk, 35% had at least 1 SS-RF. Of high-risk individuals, 70% underestimated their risk, 21% of whom perceived themselves as low risk. Engagement in health behaviours was suboptimal. Knowledge of traditional CVD risk factors and prevention was relatively high; however, less than one-half were aware of SS-RFs such as early menopause (39.4%). Conclusions Considering both traditional and SS-RFs, 47% of premenopausal Canadian women may be at risk for developing CVD. Of those deemed low medical risk for developing CVD, more than one-third reported having at least 1 SS-RF. Canadian women have poor knowledge of the risks associated with SS-RFs, lack sufficient awareness of the need for prevention of CVD, and are not engaging in sufficient health-promoting behaviours to mitigate future CVD risk.
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Affiliation(s)
- Natalie Szakun
- School of Human Kinetics, Trinity Western University, Langley, British Columbia, Canada
| | - Sarah Liva
- School of Nursing, Trinity Western University, Langley, British Columbia, Canada
| | - Michael E. Bodner
- School of Human Kinetics, Trinity Western University, Langley, British Columbia, Canada
| | - Angela Wolff
- School of Nursing, Trinity Western University, Langley, British Columbia, Canada
| | - Mi-Yeon Kim
- School of Nursing, Trinity Western University, Langley, British Columbia, Canada
| | - Anita T. Cote
- School of Human Kinetics, Trinity Western University, Langley, British Columbia, Canada
- Faculty of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada
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