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      Deep learning-based multi-modal data integration enhancing breast cancer disease-free survival prediction

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          Abstract

          Background

          The prognosis of breast cancer is often unfavorable, emphasizing the need for early metastasis risk detection and accurate treatment predictions. This study aimed to develop a novel multi-modal deep learning model using preoperative data to predict disease-free survival (DFS).

          Methods

          We retrospectively collected pathology imaging, molecular and clinical data from The Cancer Genome Atlas and one independent institution in China. We developed a novel Deep Learning Clinical Medicine Based Pathological Gene Multi-modal (DeepClinMed-PGM) model for DFS prediction, integrating clinicopathological data with molecular insights. The patients included the training cohort ( n = 741), internal validation cohort ( n = 184), and external testing cohort ( n = 95).

          Result

          Integrating multi-modal data into the DeepClinMed-PGM model significantly improved area under the receiver operating characteristic curve (AUC) values. In the training cohort, AUC values for 1-, 3-, and 5-year DFS predictions increased to 0.979, 0.957, and 0.871, while in the external testing cohort, the values reached 0.851, 0.878, and 0.938 for 1-, 2-, and 3-year DFS predictions, respectively. The DeepClinMed-PGM's robust discriminative capabilities were consistently evident across various cohorts, including the training cohort [hazard ratio (HR) 0.027, 95% confidence interval (CI) 0.0016–0.046, P < 0.0001], the internal validation cohort (HR 0.117, 95% CI 0.041–0.334, P < 0.0001), and the external cohort (HR 0.061, 95% CI 0.017–0.218, P < 0.0001). Additionally, the DeepClinMed-PGM model demonstrated C-index values of 0.925, 0.823, and 0.864 within the three cohorts, respectively.

          Conclusion

          This study introduces an approach to breast cancer prognosis, integrating imaging and molecular and clinical data for enhanced predictive accuracy, offering promise for personalized treatment strategies.

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          Most cited references41

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            Cancer statistics, 2023

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.
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              xCell: digitally portraying the tissue cellular heterogeneity landscape

              Tissues are complex milieus consisting of numerous cell types. Several recent methods have attempted to enumerate cell subsets from transcriptomes. However, the available methods have used limited sources for training and give only a partial portrayal of the full cellular landscape. Here we present xCell, a novel gene signature-based method, and use it to infer 64 immune and stromal cell types. We harmonized 1822 pure human cell type transcriptomes from various sources and employed a curve fitting approach for linear comparison of cell types and introduced a novel spillover compensation technique for separating them. Using extensive in silico analyses and comparison to cytometry immunophenotyping, we show that xCell outperforms other methods. xCell is available at http://xCell.ucsf.edu/. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1349-1) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Precis Clin Med
                Precis Clin Med
                pcm
                Precision Clinical Medicine
                Oxford University Press
                2096-5303
                2516-1571
                June 2024
                29 May 2024
                29 May 2024
                : 7
                : 2
                : pbae012
                Affiliations
                Guangdong Key Laboratory of Cross-Application of Data Science and Technology, Beijing Normal University-Hong Kong Baptist University United International College , Zhuhai 519087, China
                Faculty of Innovation Engineering, Macau University of Science and Technology , Taipa, Macao 999078, China
                Department of Computer and Information Engineering, Guangzhou Huali College , Guangzhou 511325, China
                Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou 510120, China
                Guangzhou National Laboratory , Guangzhou 510005, China
                Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet , Stockholm 17177, Sweden
                Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Breast Tumor Centre, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou 510120, China
                The Second Clinical Medical College, Southern Medical University , Guangzhou 510515, China
                Faculty of Medicine, Macau University of Science and Technology , Taipa, Macao 999078, China
                Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Breast Tumor Centre, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou 510120, China
                Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Breast Tumor Centre, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou 510120, China
                Faculty of Medicine, Macau University of Science and Technology , Taipa, Macao 999078, China
                Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Breast Tumor Centre, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou 510120, China
                Guangdong Key Laboratory of Cross-Application of Data Science and Technology, Beijing Normal University-Hong Kong Baptist University United International College , Zhuhai 519087, China
                Author notes
                Corresponding authors: Weifeng Su, wfsu@ 123456uic.edu.cn
                Corresponding authors: Herui Yao, yaoherui@ 123456mail.sysu.edu.cn
                Corresponding authors: Yunfang Yu, yuyf9@ 123456mail.sysu.edu.cn

                Zehua Wang, Ruichong Lin, Yanchun Li, and Jin Zeng contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-2913-8527
                Article
                pbae012
                10.1093/pcmedi/pbae012
                11190375
                38912415
                bf9d242e-047e-442f-a226-3081d983c6ea
                © The Author(s) 2024. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 February 2024
                : 19 May 2024
                : 22 May 2024
                : 21 June 2024
                Page count
                Pages: 14
                Funding
                Funded by: Guangdong Provincial Key Laboratory;
                Award ID: 2022B1212010006
                Award ID: UICR0600008-6
                Funded by: Guangdong Higher Education Upgrading Plan;
                Award ID: R0400001-22
                Award ID: R0400025-21
                Funded by: UIC, DOI 10.13039/100008522;
                Award ID: 2023YFE0204000
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2020A20070
                Award ID: 2021AKP0003
                Funded by: Macau Science and Technology Development Fund;
                Award ID: 2023B1212060013
                Funded by: Science and Technology Planning Project of Guangdong Province, DOI 10.13039/501100012245;
                Award ID: 82273204
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 2023A1515012412
                Award ID: 2023A1515011214
                Funded by: Guangdong Basic and Applied Basic Research Foundation, DOI 10.13039/501100021171;
                Award ID: 2023A03J0722
                Award ID: 202206010078
                Funded by: Guangzhou Science and Technology Project;
                Award ID: 2018007
                Funded by: Sun Yat-Sen University Clinical Research 5010 Program;
                Award ID: SYS-C-201801
                Funded by: Sun Yat-Sen Clinical Research Cultivating Program;
                Award ID: A2020558
                Funded by: Guangdong Medical Science and Technology Program;
                Award ID: 7670020025
                Funded by: Tencent Charity Foundation;
                Award ID: YXQH202209
                Award ID: SYSQH-II-2024–07
                Funded by: Sun Yat-sen Pilot Scientific Research Fund;
                Award ID: 2023KQNCX138
                Categories
                Research Article
                AcademicSubjects/MED00010

                breast cancer,multi-modality,deep learning,pathological,disease-free survival

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