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      ALDH1+ stem cells demonstrate more stem cell-like characteristics than CD44 +/CD24 –/low stem cells in different molecular subtypes of breast cancer

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          Abstract

          Background

          CD44 +/CD24 /low and ALDH1+ are both markers of breast cancer stem cell (BCSC), we compared the biological characteristics of CD44 +/CD24 /low and ALDH1+ BCSCs in the four molecular subtypes of breast cancer.

          Methods

          Four fresh blocks of breast cancer tissue were obtained from patients with Luminal A, Luminal B, human epidermal receptor-2 (HER2)-overexpression and triple-negative breast cancer, respectively. Flow cytometry was used to sort CD44 +/CD24 /low and ALDH1+ BCSCs. The mammosphere (MS) formation experiment and NOD/SCID mouse xenograft experiment were performed to compare the self-renewal and tumorigenic abilities of CD44 +/CD24 /low with those of ALDH1+ BCSCs.

          Results

          The proportions of CD44 +/CD24 /low BCSC and ALDH1+ BCSC in Luminal A, Luminal B, HER2 overexpression and triple-negative subtypes were 12.1% and 8.7%, 2.7% and 5.7%, 0.8% and 8.7%, 0.7% and 4.5%, respectively. The MS formation experiment demonstrated that ALDH1+ BCSC formed significantly more MSs than CD44 +/CD24 /low BCSC in the four molecular subtypes (P<0.001). The NOD/SCID mouse xenograft experiment demonstrated that the sizes of grafted tumors formed by ALDH1+ BCSC were larger than those formed by CD44 +/CD24 /low BCSC in the four molecular subtypes (P<0.05).

          Conclusions

          In the four molecular subtypes of breast cancer, ALDH1+ BCSC demonstrated better self-renewal and tumorigenic abilities than CD44 +/CD24 /low BCSC.

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          Most cited references23

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          Cancer statistics in China, 2015.

          With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population-based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.
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            Comprehensive molecular portraits of human breast tumors

            Summary We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer.
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              Cancer statistics, 2016.

              Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2016, 1,685,210 new cancer cases and 595,690 cancer deaths are projected to occur in the United States. Overall cancer incidence trends (13 oldest SEER registries) are stable in women, but declining by 3.1% per year in men (from 2009-2012), much of which is because of recent rapid declines in prostate cancer diagnoses. The cancer death rate has dropped by 23% since 1991, translating to more than 1.7 million deaths averted through 2012. Despite this progress, death rates are increasing for cancers of the liver, pancreas, and uterine corpus, and cancer is now the leading cause of death in 21 states, primarily due to exceptionally large reductions in death from heart disease. Among children and adolescents (aged birth-19 years), brain cancer has surpassed leukemia as the leading cause of cancer death because of the dramatic therapeutic advances against leukemia. Accelerating progress against cancer requires both increased national investment in cancer research and the application of existing cancer control knowledge across all segments of the population.
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                Author and article information

                Journal
                Transl Cancer Res
                Transl Cancer Res
                TCR
                Translational Cancer Research
                AME Publishing Company
                2218-676X
                2219-6803
                March 2020
                March 2020
                : 9
                : 3
                : 1652-1659
                Affiliations
                [1 ]deptDepartment of Breast Surgery, Sichuan Provincial People’s Hospital , University of Electronic Science and Technology of China , Chengdu 611731, China;
                [2 ]deptDepartment of Breast Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine , University of Electronic Science and Technology of China , Chengdu 611731, China;
                [3 ] Department of Breast and Thyroid Surgery, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi 563000, China,
                Author notes

                Contributions: (I) Conception and design: X Zhang; (II) Administrative support: J Chen; (III) Provision of study materials or patients: J Chen; (IV) Collection and assembly of data: S Liu; (V) Data analysis and interpretation: S Liu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Xiao Zhang. Department of Breast Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China. Email: BCacademic@ 123456163.com ; Yingying Su. Department of Breast and Thyroid Surgery, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi 563000, China. Email: sunny9585@ 123456163.com .
                Article
                tcr-09-03-1652
                10.21037/tcr.2020.01.53
                8798598
                35117513
                f1eeb7ec-6659-442d-b6b3-e5a09fd21eae
                2020 Translational Cancer Research. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                : 12 October 2019
                : 20 December 2019
                Funding
                Funded by: the Doctor’s Fund of Sichuan Provincial People’s Hospital
                Categories
                Original Article

                breast cancer,breast cancer stem cell (bcsc),cd44+/cd24–/low,aldh1+,molecular subtype

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