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Xu W, Zhang L, Qian X, Sun N, Tu X, Zhou D, Zheng X, Chen J, Xie Z, He T, Qu S, Wang Y, Yang K, Su K, Feng S, Ju B. A deep learning framework for hepatocellular carcinoma diagnosis using MS1 data. Sci Rep 2024; 14:26705. [PMID: 39496730 PMCID: PMC11535524 DOI: 10.1038/s41598-024-77494-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 10/22/2024] [Indexed: 11/06/2024] Open
Abstract
Clinical proteomics analysis is of great significance for analyzing pathological mechanisms and discovering disease-related biomarkers. Using computational methods to accurately predict disease types can effectively improve patient disease diagnosis and prognosis. However, how to eliminate the errors introduced by peptide precursor identification and protein identification for pathological diagnosis remains a major unresolved issue. Here, we develop a powerful end-to-end deep learning model, termed "MS1Former", that is able to classify hepatocellular carcinoma tumors and adjacent non-tumor (normal) tissues directly using raw MS1 spectra without peptide precursor identification. Our model provides accurate discrimination of subtle m/z differences in MS1 between tumor and adjacent non-tumor tissue, as well as more general performance predictions for data-dependent acquisition, data-independent acquisition, and full-scan data. Our model achieves the best performance on multiple external validation datasets. Additionally, we perform a detailed exploration of the model's interpretability. Prospectively, we expect that the advanced end-to-end framework will be more applicable to the classification of other tumors.
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Affiliation(s)
- Wei Xu
- College of Basic Medical Science, Zhejiang Chinese Medical University, 548 Binwen Rd, Hangzhou, 310053, China
- Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, 548 Binwen Rd, Hangzhou, 310053, China
| | - Liying Zhang
- SanOmics AI Co., Ltd, Lingping District, Hangzhou, 311103, China
| | - Xiaoliang Qian
- SanOmics AI Co., Ltd, Lingping District, Hangzhou, 311103, China
| | - Nannan Sun
- SanOmics AI Co., Ltd, Lingping District, Hangzhou, 311103, China
| | - Xiao Tu
- College of Basic Medical Science, Zhejiang Chinese Medical University, 548 Binwen Rd, Hangzhou, 310053, China
- Key Laboratory of Zhejiang Province, Management of Kidney Disease, Hangzhou, 310000, China
| | - Dengfeng Zhou
- SanOmics AI Co., Ltd, Lingping District, Hangzhou, 311103, China
| | - Xiaoping Zheng
- Pathology Department, Shulan (Hangzhou) Hospital, Hangzhou, China
| | - Jia Chen
- School of Life Sciences, Key Laboratory of Structural Biology of Zhejiang Province, Westlake University, Hangzhou, 310024, China
- The Biomedical Research Core Facility, Mass Spectrometry and Metabolomics Core Facility, Westlake University, Hangzhou, 310024, China
| | - Zewen Xie
- SanOmics AI Co., Ltd, Lingping District, Hangzhou, 311103, China
| | - Tao He
- SanOmics AI Co., Ltd, Lingping District, Hangzhou, 311103, China
| | - Shugang Qu
- SanOmics AI Co., Ltd, Lingping District, Hangzhou, 311103, China
| | - Yinjia Wang
- The First People's Hospital of Kunming, Intensive Care Unit, Kunming, 650032, China.
| | - Keda Yang
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310015, China.
| | - Kunkai Su
- The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310013, China.
| | - Shan Feng
- School of Life Sciences, Key Laboratory of Structural Biology of Zhejiang Province, Westlake University, Hangzhou, 310024, China.
- The Biomedical Research Core Facility, Mass Spectrometry and Metabolomics Core Facility, Westlake University, Hangzhou, 310024, China.
| | - Bin Ju
- SanOmics AI Co., Ltd, Lingping District, Hangzhou, 311103, China.
- Innovative Institute of Basic Medical Sciences, Zhejiang University, Hangzhou, 310022, Zhejiang, China.
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Cardoso Rial R. AI in analytical chemistry: Advancements, challenges, and future directions. Talanta 2024; 274:125949. [PMID: 38569367 DOI: 10.1016/j.talanta.2024.125949] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/09/2024] [Accepted: 03/17/2024] [Indexed: 04/05/2024]
Abstract
This article explores the influence and applications of Artificial Intelligence (AI) in analytical chemistry, highlighting its potential to revolutionize the analysis of complex data sets and the development of innovative analytical methods. Additionally, it discusses the role of AI in interpreting large-scale data and optimizing experimental processes. AI has been fundamental in managing heterogeneous data and in advanced analysis of complex spectra in areas such as spectroscopy and chromatography. The article also examines the historical development of AI in chemistry, its current challenges, including the interpretation of AI models and the integration of large volumes of data. Finally, it forecasts future trends and the potential impact of AI on analytical chemistry, emphasizing the need for ethical and secure approaches in the use of AI.
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Affiliation(s)
- Rafael Cardoso Rial
- Federal Institute of Mato Grosso do Sul, 79750-000, Nova Andradina, MS, Brazil.
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Huang J, Bai X, Qiu Y, He X. Application of AI on cholangiocarcinoma. Front Oncol 2024; 14:1324222. [PMID: 38347839 PMCID: PMC10859478 DOI: 10.3389/fonc.2024.1324222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 01/08/2024] [Indexed: 02/15/2024] Open
Abstract
Cholangiocarcinoma, classified as intrahepatic, perihilar, and extrahepatic, is considered a deadly malignancy of the hepatobiliary system. Most cases of cholangiocarcinoma are asymptomatic. Therefore, early detection of cholangiocarcinoma is significant but still challenging. The routine screening of a tumor lacks specificity and accuracy. With the application of AI, high-risk patients can be easily found by analyzing their clinical characteristics, serum biomarkers, and medical images. Moreover, AI can be used to predict the prognosis including recurrence risk and metastasis. Although they have some limitations, AI algorithms will still significantly improve many aspects of cholangiocarcinoma in the medical field with the development of computing power and technology.
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Affiliation(s)
| | | | | | - Xiaodong He
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Vlocskó M, Piffkó J, Janovszky Á. Intraoperative Assessment of Resection Margin in Oral Cancer: The Potential Role of Spectroscopy. Cancers (Basel) 2023; 16:121. [PMID: 38201548 PMCID: PMC10777979 DOI: 10.3390/cancers16010121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 12/21/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024] Open
Abstract
In parallel with the increasing number of oncological cases, the need for faster and more efficient diagnostic tools has also appeared. Different diagnostic approaches are available, such as radiological imaging or histological staining methods, but these do not provide adequate information regarding the resection margin, intraoperatively, or are time consuming. The purpose of this review is to summarize the current knowledge on spectrometric diagnostic modalities suitable for intraoperative use, with an emphasis on their relevance in the management of oral cancer. The literature agrees on the sensitivity, specificity, and accuracy of spectrometric diagnostic modalities, but further long-term prospective, multicentric clinical studies are needed, which may standardize the intraoperative assessment of the resection margin and the use of real-time spectroscopic approaches.
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Affiliation(s)
| | | | - Ágnes Janovszky
- Department of Oral and Maxillofacial Surgery, Albert Szent-Györgyi Medical School, University of Szeged, Kálvária 57, H-6725 Szeged, Hungary; (M.V.); (J.P.)
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King ME, Lin M, Spradlin M, Eberlin LS. Advances and Emerging Medical Applications of Direct Mass Spectrometry Technologies for Tissue Analysis. ANNUAL REVIEW OF ANALYTICAL CHEMISTRY (PALO ALTO, CALIF.) 2023; 16:1-25. [PMID: 36944233 DOI: 10.1146/annurev-anchem-061020-015544] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Offering superb speed, chemical specificity, and analytical sensitivity, direct mass spectrometry (MS) technologies are highly amenable for the molecular analysis of complex tissues to aid in disease characterization and help identify new diagnostic, prognostic, and predictive markers. By enabling detection of clinically actionable molecular profiles from tissues and cells, direct MS technologies have the potential to guide treatment decisions and transform sample analysis within clinical workflows. In this review, we highlight recent health-related developments and applications of direct MS technologies that exhibit tangible potential to accelerate clinical research and disease diagnosis, including oncological and neurodegenerative diseases and microbial infections. We focus primarily on applications that employ direct MS technologies for tissue analysis, including MS imaging technologies to map spatial distributions of molecules in situ as well as handheld devices for rapid in vivo and ex vivo tissue analysis.
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Affiliation(s)
- Mary E King
- Department of Chemistry, The University of Texas at Austin, Austin, Texas, USA;
- Department of Surgery, Baylor College of Medicine, Houston, Texas, USA;
| | - Monica Lin
- Department of Chemistry, The University of Texas at Austin, Austin, Texas, USA;
| | - Meredith Spradlin
- Department of Chemistry, The University of Texas at Austin, Austin, Texas, USA;
| | - Livia S Eberlin
- Department of Surgery, Baylor College of Medicine, Houston, Texas, USA;
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Gigante E, Cazier H, Albuquerque M, Laouirem S, Beaufrère A, Paradis V. MALDI Imaging, a Powerful Multiplex Approach to Decipher Intratumoral Heterogeneity: Combined Hepato-Cholangiocarcinomas as Proof of Concept. Cancers (Basel) 2023; 15:cancers15072143. [PMID: 37046807 PMCID: PMC10093162 DOI: 10.3390/cancers15072143] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/27/2023] [Accepted: 03/29/2023] [Indexed: 04/08/2023] Open
Abstract
Combined hepato-cholangiocarcinomas (cHCC-CCA) belong to the spectrum of primary liver carcinomas, which include hepatocellular carcinomas (HCC) and intrahepatic cholangiocarcinomas (iCCA) at both ends of the spectrum. Mainly due to the high intratumor heterogeneity of cHCC-CCA, its diagnosis and pathological description remain challenging. Taking advantage of in situ non-targeted molecular mapping provided by MALDI (Matrix Assisted Laser Desorption Ionization) imaging, we sought to develop a multiscale and multiparametric morphological approach, integrating molecular and conventional pathological analysis. MALDI imaging was applied to five representative cases of resected cHCC-CCA. Principal component analysis and segmentations with MALDI imaging techniques identified areas related to either iCCA or HCC and also hidden tumor areas not visible microscopically. In addition, the overlap between MALDI segmentation and immunostaining provided a comprehensive description of cHCC-CCA tumor heterogeneity by identifying transitional and micro-metastatic areas. Moreover, a list of peptides derived from in silico digestion was obtained for each immunohistochemical marker and was matched within the peptide peak list acquired by MALDI. Comparison of immunostaining images with ions from in silico digestion revealed an accurate identification of iCCA and HCC areas. Our study provides further evidence on the performance of MALDI imaging in exploring intratumor heterogeneity and offering virtual multiplex immunostaining through a single acquisition.
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Affiliation(s)
- Elia Gigante
- Centre de Recherche sur L'inflammation, Inserm, Université Paris Cité, F-75018 Paris, France
- Service d’Hépato-Gastroentérologie et Cancérologie Digestive, Hôpital Robert Debré, F-51090 Reims, France
| | - Hélène Cazier
- Centre de Recherche sur L'inflammation, Inserm, Université Paris Cité, F-75018 Paris, France
- Plateforme iMAP, Centre de Recherche sur L'inflammation, Inserm, Université Paris Cité, F-75018 Paris, France
| | - Miguel Albuquerque
- Département de Pathologie, Assistance Publique-Hôpitaux de Paris, FHU MOSAIC, Hôpital Beaujon, F-92110 Clichy, France
| | - Samira Laouirem
- Centre de Recherche sur L'inflammation, Inserm, Université Paris Cité, F-75018 Paris, France
| | - Aurélie Beaufrère
- Centre de Recherche sur L'inflammation, Inserm, Université Paris Cité, F-75018 Paris, France
- Département de Pathologie, Assistance Publique-Hôpitaux de Paris, FHU MOSAIC, Hôpital Beaujon, F-92110 Clichy, France
| | - Valérie Paradis
- Centre de Recherche sur L'inflammation, Inserm, Université Paris Cité, F-75018 Paris, France
- Département de Pathologie, Assistance Publique-Hôpitaux de Paris, FHU MOSAIC, Hôpital Beaujon, F-92110 Clichy, France
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Xiong M, Xu Y, Zhao Y, He S, Zhu Q, Wu Y, Hu X, Liu L. Quantitative analysis of artificial intelligence on liver cancer: A bibliometric analysis. Front Oncol 2023; 13:990306. [PMID: 36874099 PMCID: PMC9978515 DOI: 10.3389/fonc.2023.990306] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 02/03/2023] [Indexed: 02/18/2023] Open
Abstract
Objective To provide the current research progress, hotspots, and emerging trends for AI in liver cancer, we have compiled a relative comprehensive and quantitative report on the research of liver disease using artificial intelligence by employing bibliometrics in this study. Methods In this study, the Web of Science Core Collection (WoSCC) database was used to perform systematic searches using keywords and a manual screening strategy, VOSviewer was used to analyze the degree of cooperation between countries/regions and institutions, as well as the co-occurrence of cooperation between authors and cited authors. Citespace was applied to generate a dual map to analyze the relationship of citing journals and citied journals and conduct a strong citation bursts ranking analysis of references. Online SRplot was used for in-depth keyword analysis and Microsoft Excel 2019 was used to collect the targeted variables from retrieved articles. Results 1724 papers were collected in this study, including 1547 original articles and 177 reviews. The study of AI in liver cancer mostly began from 2003 and has developed rapidly from 2017. China has the largest number of publications, and the United States has the highest H-index and total citation counts. The top three most productive institutions are the League of European Research Universities, Sun Yat Sen University, and Zhejiang University. Jasjit S. Suri and Frontiers in Oncology are the most published author and journal, respectively. Keyword analysis showed that in addition to the research on liver cancer, research on liver cirrhosis, fatty liver disease, and liver fibrosis were also common. Computed tomography was the most used diagnostic tool, followed by ultrasound and magnetic resonance imaging. The diagnosis and differential diagnosis of liver cancer are currently the most widely adopted research goals, and comprehensive analyses of multi-type data and postoperative analysis of patients with advanced liver cancer are rare. The use of convolutional neural networks is the main technical method used in studies of AI on liver cancer. Conclusion AI has undergone rapid development and has a wide application in the diagnosis and treatment of liver diseases, especially in China. Imaging is an indispensable tool in this filed. Mmulti-type data fusion analysis and development of multimodal treatment plans for liver cancer could become the major trend of future research in AI in liver cancer.
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Affiliation(s)
- Ming Xiong
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yaona Xu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yang Zhao
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Si He
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qihan Zhu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yi Wu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaofei Hu
- Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Li Liu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China.,Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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Hakoda H, Kiritani S, Kokudo T, Yoshimura K, Iwano T, Tanimoto M, Ishizawa T, Arita J, Akamatsu N, Kaneko J, Takeda S, Hasegawa K. Probe electrospray ionization mass spectrometry-based rapid diagnosis of liver tumors. J Gastroenterol Hepatol 2022; 37:2182-2188. [PMID: 35945170 DOI: 10.1111/jgh.15976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 07/28/2022] [Accepted: 08/03/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Prompt differential diagnosis of liver tumors is clinically important and sometimes difficult. A new diagnostic device that combines probe electrospray ionization-mass spectrometry (PESI-MS) and machine learning may help provide the differential diagnosis of liver tumors. METHODS We evaluated the diagnostic accuracy of this new PESI-MS device using tissues obtained and stored from previous surgically resected specimens. The following cancer tissues (with collection dates): hepatocellular carcinoma (HCC, 2016-2019), intrahepatic cholangiocellular carcinoma (ICC, 2014-2019), and colorectal liver metastasis (CRLM, 2014-2019) from patients who underwent hepatic resection were considered for use in this study. Non-cancerous liver tissues (NL) taken from CRLM cases were also incorporated into the analysis. Each mass spectrum provided by PESI-MS was tested using support vector machine, a type of machine learning, to evaluate the discriminatory ability of the device. RESULTS In this study, we used samples from 91 of 139 patients with HCC, all 24 ICC samples, and 103 of 202 CRLM samples; 80 NL from CRLM cases were also used. Each mass spectrum was obtained by PESI-MS in a few minutes and was evaluated by machine learning. The sensitivity, specificity, and diagnostic accuracy of the PESI-MS device for discriminating HCC, ICC, and CRLM from among a mix of all three tumors and from NL were 98.9%, 98.1%, and 98.3%; 87.5%, 93.1%, and 92.6%; and 99.0%, 97.9%, and 98.3%, respectively. CONCLUSION This study demonstrated that PESI-MS and machine learning could discriminate liver tumors accurately and rapidly.
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Affiliation(s)
- Hiroyuki Hakoda
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Sho Kiritani
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kentaro Yoshimura
- Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
| | - Tomohiko Iwano
- Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
| | - Meguri Tanimoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takeaki Ishizawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Sen Takeda
- Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
- Department of Anatomy, Teikyo University School of Medicine, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Preliminary Evaluation of Artificial Intelligence-Based Anti-Hepatocellular Carcinoma Molecular Target Study in Hepatocellular Carcinoma Diagnosis Research. BIOMED RESEARCH INTERNATIONAL 2022; 2022:8365565. [PMID: 36193305 PMCID: PMC9526586 DOI: 10.1155/2022/8365565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/21/2022] [Accepted: 08/29/2022] [Indexed: 11/18/2022]
Abstract
In this paper, in-depth research analysis of anti-hepatocellular carcinoma molecular targets for hepatocellular carcinoma diagnosis was conducted using artificial intelligence. Because BRD4 plays an important role in gene transcription for cell cycle regulation and apoptosis, tumor-targeted therapy by inhibiting the expression or function of BRD4 has received increasing attention in the field of antitumor research. Study subjects in small samples were used as the validation set for validating each diagnostic model constructed based on the training set. The diagnostic effect of each model in the validation set is evaluated by calculating the sensitivity, specificity, and compliance rate, and the model with the best and most stable diagnostic value is selected by combining the results of model construction, validation, and evaluation. The total sample was divided into a training set and test set by using a stratified sampling method in the ratio of 7 : 3. Logistic regression, weighted k-nearest neighbor, decision tree, and BP artificial neural network were used in the training set to construct diagnostic models for early-stage liver cancer, respectively, and the optimal parameters of the corresponding models were obtained, and then, the constructed models were validated in the test set. To evaluate the diagnostic efficacy, stability, and generalization ability of the four classification methods more robustly, a 10-fold crossover test was performed for each classification method. BRD4 is an epigenetic regulator that is associated with the upregulation of expression of various oncogenic drivers in tumors. Targeting BRD4 with pharmacological inhibitors has emerged as a novel approach for tumor treatment. However, before we implemented this topic, there were no detailed studies on whether BRD4 could be used for the treatment of HCC, the role of BRD4 in HCC cell proliferation and apoptosis, and the ability of small molecule BRD4 inhibitors to induce apoptosis in hepatocellular carcinoma cells.
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Wang Y, Chen Z, Shima K, Zhong D, Yang L, Wang Q, Jiang R, Dong J, Lei Y, Li X, Cao L. Rapid diagnosis of papillary thyroid carcinoma with machine learning and probe electrospray ionization mass spectrometry. JOURNAL OF MASS SPECTROMETRY : JMS 2022; 57:e4831. [PMID: 35562642 DOI: 10.1002/jms.4831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 04/21/2022] [Accepted: 04/22/2022] [Indexed: 06/15/2023]
Abstract
Frozen section examination could provide pathological diagnosis for surgery of thyroid nodules, which is time-consuming, skill- and experience-dependent. This study developed a rapid classification method for thyroid nodules and machine learning. Total 69 tissues were collected including 43 nodules and 26 nodule-adjacent tissues. Intraoperative frozen section was first performed to give accurate diagnosis, and the rest frozen specimen were pretreated for probe electrospray ionization mass measurement. By multivariate analysis of mass scan data, a series compounds were found downregulated in the extraction solution of papillary thyroid carcinoma (PTC), but some were found upregulated by mass spectrometry imaging. m/z 758.5713 ([PC[34:2] + H]+ ), m/z 772.5845 ([PC[32:0] + K]+ ), and m/z 786.6037 ([PC[36:2] + H]+ ) were firstly identified as potential biomarkers for nodular goiter (NG). Machine learning was employed by means of support vector machine (SVM) and random forest (RF) algorithms. For classification of PTC from NG, SVM and RF algorithms exhibited the same performance and the concordance was 94.2% and 94.4% between prediction and pathological diagnosis with positive and negative mass dataset, respectively. For the classification of PTC from PTC adjacent tissues, SVM was better than RF and the concordance was 93.8% and 83.3% with positive and negative mass dataset, respectively. With the identified compounds as training features, the sensitivity and specificity are 87.5% and 88.9% for the test set. The developed method could also correctly predict the malignancy of one medullary thyroid carcinoma and one adenomatous goiter (benign). The diagnosis time is about 10 min for one specimen, and it is very promising for the intraoperative diagnosis of papillary thyroid carcinoma.
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Affiliation(s)
- Ye Wang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Zhenhe Chen
- Shimadzu China Innovation Center, Shimadzu Corporation, Beijing, China
| | - Keisuke Shima
- Shimadzu China Innovation Center, Shimadzu Corporation, Beijing, China
| | - Dingrong Zhong
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Lei Yang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Qingyang Wang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Ruiying Jiang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Jing Dong
- Shimadzu China Innovation Center, Shimadzu Corporation, Beijing, China
| | - Yajuan Lei
- Shimadzu China Innovation Center, Shimadzu Corporation, Beijing, China
| | - Xiaodong Li
- Shimadzu China Innovation Center, Shimadzu Corporation, Beijing, China
| | - Lei Cao
- Shimadzu China Innovation Center, Shimadzu Corporation, Beijing, China
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Chen HY, Ge P, Liu JY, Qu JL, Bao F, Xu CM, Chen HL, Shang D, Zhang GX. Artificial intelligence: Emerging player in the diagnosis and treatment of digestive disease. World J Gastroenterol 2022; 28:2152-2162. [PMID: 35721881 PMCID: PMC9157617 DOI: 10.3748/wjg.v28.i20.2152] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/24/2021] [Accepted: 04/24/2022] [Indexed: 02/06/2023] Open
Abstract
Given the breakthroughs in key technologies, such as image recognition, deep learning and neural networks, artificial intelligence (AI) continues to be increasingly developed, leading to closer and deeper integration with an increasingly data-, knowledge- and brain labor-intensive medical industry. As society continues to advance and individuals become more aware of their health needs, the problems associated with the aging of the population are receiving increasing attention, and there is an urgent demand for improving medical technology, prolonging human life and enhancing health. Digestive system diseases are the most common clinical diseases and are characterized by complex clinical manifestations and a general lack of obvious symptoms in the early stage. Such diseases are very difficult to diagnose and treat. In recent years, the incidence of diseases of the digestive system has increased. As AI applications in the field of health care continue to be developed, AI has begun playing an important role in the diagnosis and treatment of diseases of the digestive system. In this paper, the application of AI in assisted diagnosis and the application and prospects of AI in malignant and benign digestive system diseases are reviewed.
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Affiliation(s)
- Hai-Yang Chen
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Peng Ge
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Jia-Yue Liu
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Jia-Lin Qu
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Fang Bao
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Cai-Ming Xu
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Hai-Long Chen
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Dong Shang
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Gui-Xin Zhang
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China
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12
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Fast Classification of Thyroid Nodules with Ultrasound Guided-Fine Needle Biopsy Samples and Machine Learning. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12115364] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
A rapid classification method was developed for the malignant and benign thyroid nodules with ultrasound guided-fine needle aspiration biopsy (FNAB) samples. With probe electrospray ionization mass spectrometry, the mass-scan data of FNAB samples were used as datasets for machine learning. The patients were marked as malignant (98 patients), benign (110 patients) or undetermined (42 patients) by experienced doctors in terms of ultrasound, the B-Raf (BRAF) gene, and cytopathology inspections. Pairwise coupling was performed on 163 ions to generate 3630 ion ratios as new features for classifier training. With the new features, the performance of the multilayer perception (MLP) classifier is much better than that with the 163 ions as features directly. After training, the accuracy of the MLP classifier is as high as 92.0%. The accuracy of the single-blind test is 82.4%, which proved the good generalization ability of the MLP classifier. The overall concordance is 73.0% between prediction and six-month follow-up for patients in the undetermined group. Especially, the classifier showed high accuracy for the undetermined patients with suspicious for papillary carcinoma diagnosis (90.9%). In summary, the machine learning method based on FNAB samples has potential for real clinical applications.
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13
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Giordano S, Siciliano AM, Donadon M, Soldani C, Franceschini B, Lleo A, Di Tommaso L, Cimino M, Torzilli G, Saiki H, Nakajima H, Takeda S, Davoli E. Versatile Mass Spectrometry-Based Intraoperative Diagnosis of Liver Tumor in a Multiethnic Cohort. APPLIED SCIENCES 2022; 12:4244. [DOI: 10.3390/app12094244] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Currently used techniques for intraoperative assessment of tumor resection margins are time-consuming and laborious and, more importantly, lack specificity. Moreover, pathological diagnosis during surgery does not often give a clear outcome. Recent advances in mass spectrometry (MS) and instrumentation have made it possible to obtain detailed molecular information from tissue specimens in real-time, with minimal sample pre-treatment. Probe Electro Spray Ionization MS (PESI-MS), combined with artificial intelligence (AI), has demonstrated its effectiveness in distinguishing liver cancer tissues from healthy tissues in a large Italian population group. As the MS profile can reflect the patient’s ethnicity, dietary habits, or particular operating room procedures, the AI algorithm must be well trained to distinguish different groups. We used a large dataset composed of liver tumor and healthy specimens, from the Italian and Japanese populations, to develop a versatile algorithm free from ethnic bias. The system can classify tissues with discrepancies <5% from the pathologist’s diagnosis. These results demonstrate the potential of the PESI-MS system to distinguish tumor from surrounding non-tumor tissues in patients, with minimal bias from race/ethnicity or etiological characteristics or operating room procedures.
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Affiliation(s)
- Silvia Giordano
- Shimadzu Italia S.r.l., Via G.B. Cassinis, 7, 20139 Milano, Italy
| | - Angela Marika Siciliano
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy
| | - Matteo Donadon
- Department of Biomedical Science, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy
- Laboratory of Hepatobiliary Immunopathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy
| | - Cristiana Soldani
- Laboratory of Hepatobiliary Immunopathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy
| | - Barbara Franceschini
- Laboratory of Hepatobiliary Immunopathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy
| | - Ana Lleo
- Department of Biomedical Science, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy
- Laboratory of Hepatobiliary Immunopathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy
- Internal Medicine and Hepatology Unit, Department of Gastroenterology, Humanitas Clinical and Research Hospital—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Luca Di Tommaso
- Department of Biomedical Science, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy
- Department of Pathology, Humanitas University, Humanitas Clinical and Research Hospital—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Matteo Cimino
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy
- Laboratory of Hepatobiliary Immunopathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy
| | - Guido Torzilli
- Department of Biomedical Science, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy
| | | | | | - Sen Takeda
- Department of Anatomy, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi, Tokyo 173-8605, Japan
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Yamanashi, 1110, Chuo, Yamanashi 409-3898, Japan
| | - Enrico Davoli
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy
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14
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Christou CD, Tsoulfas G. Role of three-dimensional printing and artificial intelligence in the management of hepatocellular carcinoma: Challenges and opportunities. World J Gastrointest Oncol 2022; 14:765-793. [PMID: 35582107 PMCID: PMC9048537 DOI: 10.4251/wjgo.v14.i4.765] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 08/24/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) constitutes the fifth most frequent malignancy worldwide and the third most frequent cause of cancer-related deaths. Currently, treatment selection is based on the stage of the disease. Emerging fields such as three-dimensional (3D) printing, 3D bioprinting, artificial intelligence (AI), and machine learning (ML) could lead to evidence-based, individualized management of HCC. In this review, we comprehensively report the current applications of 3D printing, 3D bioprinting, and AI/ML-based models in HCC management; we outline the significant challenges to the broad use of these novel technologies in the clinical setting with the goal of identifying means to overcome them, and finally, we discuss the opportunities that arise from these applications. Notably, regarding 3D printing and bioprinting-related challenges, we elaborate on cost and cost-effectiveness, cell sourcing, cell viability, safety, accessibility, regulation, and legal and ethical concerns. Similarly, regarding AI/ML-related challenges, we elaborate on intellectual property, liability, intrinsic biases, data protection, cybersecurity, ethical challenges, and transparency. Our findings show that AI and 3D printing applications in HCC management and healthcare, in general, are steadily expanding; thus, these technologies will be integrated into the clinical setting sooner or later. Therefore, we believe that physicians need to become familiar with these technologies and prepare to engage with them constructively.
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Affiliation(s)
- Chrysanthos D Christou
- Department of Transplantation Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54622, Greece
| | - Georgios Tsoulfas
- Department of Transplantation Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54622, Greece
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15
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Shigeeda W, Yosihimura R, Fujita Y, Saiki H, Deguchi H, Tomoyasu M, Kudo S, Kaneko Y, Kanno H, Inoue Y, Saito H. Utility of mass spectrometry and artificial intelligence for differentiating primary lung adenocarcinoma and colorectal metastatic pulmonary tumor. Thorac Cancer 2021; 13:202-209. [PMID: 34812577 PMCID: PMC8758431 DOI: 10.1111/1759-7714.14246] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/07/2021] [Accepted: 11/08/2021] [Indexed: 11/27/2022] Open
Abstract
Background Rapid intraoperative diagnosis for unconfirmed pulmonary tumor is extremely important for determining the optimal surgical procedure (lobectomy or sublobar resection). Attempts to diagnose malignant tumors using mass spectrometry (MS) have recently been described. This study evaluated the usefulness of MS and artificial intelligence (AI) for differentiating primary lung adenocarcinoma (PLAC) and colorectal metastatic pulmonary tumor. Methods Pulmonary samples from 40 patients who underwent pulmonary resection for PLAC (20 tumors, 20 normal lungs) or pulmonary metastases originating from colorectal metastatic pulmonary tumor (CRMPT) (20 tumors, 20 normal lungs) were collected and analyzed retrospectively by probe electrospray ionization‐MS. AI using random forest (RF) algorithms was employed to evaluate the accuracy of each combination. Results The accuracy of the machine learning algorithm applied using RF to distinguish malignant tumor (PLAC or CRMPT) from normal lung was 100%. The algorithms offered 97.2% accuracy in differentiating PLAC and CRMPT. Conclusions MS combined with an AI system demonstrated high accuracy not only for differentiating cancer from normal tissue, but also for differentiating between PLAC and CRMPT with a short working time. This method shows potential for application as a support tool facilitating rapid intraoperative diagnosis to determine the surgical procedure for pulmonary resection.
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Affiliation(s)
- Wataru Shigeeda
- Department of Thoracic Surgery, Iwate Medical University, Iwate, Japan
| | | | - Yuji Fujita
- Division of Critical Care Medicine, Department of Critical Care, Disaster and General Medicine, Iwate Medical University, Iwate, Japan
| | | | - Hiroyuki Deguchi
- Department of Thoracic Surgery, Iwate Medical University, Iwate, Japan
| | - Makoto Tomoyasu
- Department of Thoracic Surgery, Iwate Medical University, Iwate, Japan
| | - Satoshi Kudo
- Department of Thoracic Surgery, Iwate Medical University, Iwate, Japan
| | - Yuka Kaneko
- Department of Thoracic Surgery, Iwate Medical University, Iwate, Japan
| | - Hironaga Kanno
- Department of Thoracic Surgery, Iwate Medical University, Iwate, Japan
| | - Yoshihiro Inoue
- Division of Critical Care Medicine, Department of Critical Care, Disaster and General Medicine, Iwate Medical University, Iwate, Japan
| | - Hajime Saito
- Department of Thoracic Surgery, Iwate Medical University, Iwate, Japan
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16
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Anteby R, Klang E, Horesh N, Nachmany I, Shimon O, Barash Y, Kopylov U, Soffer S. Deep learning for noninvasive liver fibrosis classification: A systematic review. Liver Int 2021; 41:2269-2278. [PMID: 34008300 DOI: 10.1111/liv.14966] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/23/2021] [Accepted: 05/13/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS While biopsy is the gold standard for liver fibrosis staging, it poses significant risks. Noninvasive assessment of liver fibrosis is a growing field. Recently, deep learning (DL) technology has revolutionized medical image analysis. This technology has the potential to enhance noninvasive fibrosis assessment. We systematically examined the application of DL in noninvasive liver fibrosis imaging. METHODS Embase, MEDLINE, Web of Science, and IEEE Xplore databases were used to identify studies that reported on the accuracy of DL for classification of liver fibrosis on noninvasive imaging. The search keywords were "liver or hepatic," "fibrosis or cirrhosis," and "neural or DL networks." Risk of bias and applicability were evaluated using the QUADAS-2 tool. RESULTS Sixteen studies were retrieved. Imaging modalities included ultrasound (n = 10), computed tomography (n = 3), and magnetic resonance imaging (n = 3). The studies analyzed a total of 40 405 radiological images from 15 853 patients. All but two of the studies were retrospective. In most studies the "ground truth" reference was the METAVIR score for pathological staging (n = 9.56%). The majority of the studies reported an accuracy >85% when compared to histopathology. Fourteen studies (87.5%) had a high risk of bias and concerns regarding applicability. CONCLUSIONS Deep learning has the potential to play an emerging role in liver fibrosis classification. Yet, it is still limited by a relatively small number of retrospective studies. Clinicians should facilitate the use of this technology by sharing databases and standardized reports. This may optimize the noninvasive evaluation of liver fibrosis on a large scale.
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Affiliation(s)
- Roi Anteby
- School of Public Health, Harvard University, Boston, MA, USA
| | - Eyal Klang
- Department of Population Health Science and Policy, Institute for Healthcare Delivery Science, New York, NY, USA.,Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.,Deep Vision Lab, The Chaim Sheba Medical Center, Ramat Gan, Israel.,Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel
| | - Nir Horesh
- Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.,Department of Surgery and Transplantation B, Sheba Medical Center, Tel Hashomer, Israel
| | - Ido Nachmany
- Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.,Department of Surgery and Transplantation B, Sheba Medical Center, Tel Hashomer, Israel
| | - Orit Shimon
- Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.,Department of Anesthesia, Rabin Medical Center, Beilinson Hospital, Petach Tikvah, Israel
| | - Yiftach Barash
- Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.,Deep Vision Lab, The Chaim Sheba Medical Center, Ramat Gan, Israel.,Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel
| | - Uri Kopylov
- Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.,Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel
| | - Shelly Soffer
- Deep Vision Lab, The Chaim Sheba Medical Center, Ramat Gan, Israel.,Internal Medicine B, Assuta Medical Center, Ashdod, Israel.,Ben-Gurion University of the Negev, Be'er Sheva, Israel
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17
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Katz L, Tata A, Woolman M, Zarrine-Afsar A. Lipid Profiling in Cancer Diagnosis with Hand-Held Ambient Mass Spectrometry Probes: Addressing the Late-Stage Performance Concerns. Metabolites 2021; 11:metabo11100660. [PMID: 34677375 PMCID: PMC8537725 DOI: 10.3390/metabo11100660] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/18/2021] [Accepted: 09/22/2021] [Indexed: 02/06/2023] Open
Abstract
Untargeted lipid fingerprinting with hand-held ambient mass spectrometry (MS) probes without chromatographic separation has shown promise in the rapid characterization of cancers. As human cancers present significant molecular heterogeneities, careful molecular modeling and data validation strategies are required to minimize late-stage performance variations of these models across a large population. This review utilizes parallels from the pitfalls of conventional protein biomarkers in reaching bedside utility and provides recommendations for robust modeling as well as validation strategies that could enable the next logical steps in large scale assessment of the utility of ambient MS profiling for cancer diagnosis. Six recommendations are provided that range from careful initial determination of clinical added value to moving beyond just statistical associations to validate lipid involvements in disease processes mechanistically. Further guidelines for careful selection of suitable samples to capture expected and unexpected intragroup variance are provided and discussed in the context of demographic heterogeneities in the lipidome, further influenced by lifestyle factors, diet, and potential intersect with cancer lipid pathways probed in ambient mass spectrometry profiling studies.
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Affiliation(s)
- Lauren Katz
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada; (L.K.); (M.W.)
- Techna Institute for the Advancement of Technology for Health, University Health Network, 100 College Street, Toronto, ON M5G 1P5, Canada
| | - Alessandra Tata
- Laboratorio di Chimica Sperimentale, Istituto Zooprofilattico delle Venezie, Viale Fiume 78, 36100 Vicenza, Italy;
| | - Michael Woolman
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada; (L.K.); (M.W.)
- Techna Institute for the Advancement of Technology for Health, University Health Network, 100 College Street, Toronto, ON M5G 1P5, Canada
| | - Arash Zarrine-Afsar
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada; (L.K.); (M.W.)
- Techna Institute for the Advancement of Technology for Health, University Health Network, 100 College Street, Toronto, ON M5G 1P5, Canada
- Department of Surgery, University of Toronto, 149 College Street, Toronto, ON M5T 1P5, Canada
- Keenan Research Center for Biomedical Science & the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
- Correspondence: ; Tel.: +1-416-581-8473
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18
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Chronic Liver Disease and Liver Cancer: What the Hepatologists, Oncologists, and Surgeons Want to Know from Radiologists. Magn Reson Imaging Clin N Am 2021; 29:269-278. [PMID: 34243916 DOI: 10.1016/j.mric.2021.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Effective communication between radiologists and physicians involved in the management of patients with chronic liver disease is paramount to ensuring appropriate and advantageous incorporation of liver imaging findings into patient care. This review discusses the clinical benefits of innovations in radiology reporting, what information the various stakeholders wish to know from the radiologist, and how radiology can help to ensure the effective communication of findings.
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19
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Fukuhara S, Iwasaki E, Iwano T, Machida Y, Tamagawa H, Kawasaki S, Seino T, Yokose T, Endo Y, Yoshimura K, Kashiwagi K, Kitago M, Ogata H, Takeda S, Kanai T. New strategy for evaluating pancreatic tissue specimens from endoscopic ultrasound-guided fine needle aspiration and surgery. JGH OPEN 2021; 5:953-958. [PMID: 34386605 PMCID: PMC8341188 DOI: 10.1002/jgh3.12617] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/03/2021] [Accepted: 07/07/2021] [Indexed: 01/07/2023]
Abstract
Background and Aim Preoperative histological evaluation of pancreatic neoplasms is important for guiding the resection strategy and preventing postoperative adverse events. However, conventional endoscopic methods have technical limitations that reduce the accuracy of the histopathological examination. Probe electrospray ionization mass spectrometry (PESI‐MS) may be a useful technique for rapidly evaluating small specimens. Methods This single‐center prospective study included patients with pancreatic neoplasms between October 2018 and December 2019. Pancreatic ductal adenocarcinoma (PDAC) specimens were obtained via endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) and non‐neoplastic tissue was obtained via surgery. Specimens were subjected to PESI‐MS and the mass spectra were analyzed using partial least squares regression‐discriminant analysis. Results The study included 40 patients with 20 nonneoplastic specimens and 19 PDAC specimens (1 case of neuroendocrine carcinoma was omitted). All nonneoplastic specimens were sufficient for PESI‐MS analysis, although only 7 of 19 PDAC specimens were sufficient for PESI‐MS analysis because of poor sample quality or insufficient quantity (<1 mg). Among the 27 analyzed cases, the mass spectra clearly differentiated between the PDAC and nonneoplastic specimens. Conclusions This study revealed that PESI‐MS could differentiate between PDAC and nonneoplastic specimens, even in cases where EUS‐FNA produced very small specimens.
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Affiliation(s)
- Seiichiro Fukuhara
- Center for Diagnostic and Therapeutic Endoscopy Keio University School of Medicine Tokyo Japan
| | - Eisuke Iwasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Tomohiko Iwano
- Department of Anatomy and Cell Biology University of Yamanashi Faculty of Medicine Yamanashi Japan
| | - Yujiro Machida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Hiroki Tamagawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Shintaro Kawasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Takashi Seino
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan
| | - Takahiro Yokose
- Department of Surgery Keio University School of Medicine Tokyo Japan
| | - Yutaka Endo
- Department of Surgery Keio University School of Medicine Tokyo Japan
| | - Kentaro Yoshimura
- Department of Anatomy and Cell Biology University of Yamanashi Faculty of Medicine Yamanashi Japan
| | - Kazuhiro Kashiwagi
- Center for Preventive Medicine Keio University School of Medicine Tokyo Japan
| | - Minoru Kitago
- Department of Surgery Keio University School of Medicine Tokyo Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy Keio University School of Medicine Tokyo Japan
| | - Sen Takeda
- Department of Anatomy and Cell Biology University of Yamanashi Faculty of Medicine Yamanashi Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Keio University School of Medicine Tokyo Japan
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20
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Morimoto Y, Oya T, Ichimura-Shimizu M, Matsumoto M, Ogawa H, Kobayashi T, Sumida S, Kakimoto T, Yamashita M, Cheng C, Tsuneyama K. Applying Probe Electrospray Ionization Mass Spectrometry to Cytological Diagnosis: A Preliminary Study by Using Cultured Lung Cancer Cells. Acta Cytol 2021; 65:430-439. [PMID: 34098551 DOI: 10.1159/000516639] [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: 12/27/2020] [Accepted: 04/18/2021] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Cytology and histology are 2 indispensable diagnostic tools for cancer diagnosis, which are rapidly increasing in importance with aging populations. We applied mass spectrometry (MS) as a rapid approach for swiftly acquiring nonmorphological information of interested cells. Conventional MS, which primarily rely on promoting ionization by pre-applying a matrix to cells, has the drawback of time-consuming both on data acquisition and analysis. As an emerging method, probe electrospray ionization-MS (PESI-MS) with a dedicated probe is capable to pierce sample and measure specimen in small amounts, either liquid or solid, without the requirement for sample pretreatment. Furthermore, PESI-MS is timesaving compared to the conventional MS. Herein, we investigated the capability of PESI-MS to characterize the cell types derived from the respiratory tract of human tissues. STUDY DESIGN PESI-MS analyses with DPiMS-2020 were performed on various type of cultured cells including 5 lung squamous cell carcinomas, 5 lung adenocarcinomas, 5 small-cell carcinomas, 4 malignant mesotheliomas, and 2 normal controls. RESULTS Several characteristic peaks were detected at around m/z 200 and 800 that were common in all samples. As expected, partial least squares-discriminant analysis of PESI-MS data distinguished the cancer cell types from normal control cells. Moreover, distinct clusters divided squamous cell carcinoma from adenocarcinoma. CONCLUSION PESI-MS presented a promising potential as a novel diagnostic modality for swiftly acquiring specific cytological information.
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Affiliation(s)
- Yuki Morimoto
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Takeshi Oya
- Department of Molecular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Mayuko Ichimura-Shimizu
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Minoru Matsumoto
- Department of Molecular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Hirohisa Ogawa
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Tomoko Kobayashi
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Satoshi Sumida
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Takumi Kakimoto
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Michiko Yamashita
- Department of Morphological Laboratory Science, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Chunmei Cheng
- Pharmacology and Histopathology, Novo Nordisk Research Centre China, Beijing, China
| | - Koichi Tsuneyama
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan,
- Department of Molecular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan,
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21
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Lang Q, Zhong C, Liang Z, Zhang Y, Wu B, Xu F, Cong L, Wu S, Tian Y. Six application scenarios of artificial intelligence in the precise diagnosis and treatment of liver cancer. Artif Intell Rev 2021. [DOI: 10.1007/s10462-021-10023-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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22
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Rankin‐Turner S, Heaney LM. Applications of ambient ionization mass spectrometry in 2020: An annual review. ANALYTICAL SCIENCE ADVANCES 2021; 2:193-212. [PMID: 38716454 PMCID: PMC10989608 DOI: 10.1002/ansa.202000135] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 06/26/2024]
Abstract
Recent developments in mass spectrometry (MS) analyses have seen a concerted effort to reduce the complexity of analytical workflows through the simplification (or removal) of sample preparation and the shortening of run-to-run analysis times. Ambient ionization mass spectrometry (AIMS) is an exemplar MS-based technology that has swiftly developed into a popular and powerful tool in analytical science. This increase in interest and demonstrable applications is down to its capacity to enable the rapid analysis of a diverse range of samples, typically in their native state or following a minimalistic sample preparation approach. The field of AIMS is constantly improving and expanding, with developments of powerful and novel techniques, improvements to existing instrumentation, and exciting new applications added with each year that passes. This annual review provides an overview of applications of AIMS techniques over the past year (2020), with a particular focus on the application of AIMS in a number of key fields of research including biomedical sciences, forensics and security, food sciences, the environment, and chemical synthesis. Novel ambient ionization techniques are introduced, including picolitre pressure-probe electrospray ionization and fiber spray ionization, in addition to modifications and improvements to existing techniques such as hand-held devices for ease of use, and USB-powered ion sources for on-site analysis. In all, the information provided in this review supports the view that AIMS has become a leading approach in MS-based analyses and that improvements to existing methods, alongside the development of novel approaches, will continue across the foreseeable future.
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Affiliation(s)
- Stephanie Rankin‐Turner
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreMarylandUSA
| | - Liam M. Heaney
- School of Sport, Exercise and Health SciencesLoughborough UniversityLoughboroughLeicestershireUK
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Moldogazieva NT, Mokhosoev IM, Zavadskiy SP, Terentiev AA. Proteomic Profiling and Artificial Intelligence for Hepatocellular Carcinoma Translational Medicine. Biomedicines 2021; 9:biomedicines9020159. [PMID: 33562077 PMCID: PMC7914649 DOI: 10.3390/biomedicines9020159] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 01/27/2021] [Accepted: 02/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver with high morbidity and mortality rates worldwide. Since 1963, when alpha-fetoprotein (AFP) was discovered as a first HCC serum biomarker, several other protein biomarkers have been identified and introduced into clinical practice. However, insufficient specificity and sensitivity of these biomarkers dictate the necessity of novel biomarker discovery. Remarkable advancements in integrated multiomics technologies for the identification of gene expression and protein or metabolite distribution patterns can facilitate rising to this challenge. Current multiomics technologies lead to the accumulation of a huge amount of data, which requires clustering and finding correlations between various datasets and developing predictive models for data filtering, pre-processing, and reducing dimensionality. Artificial intelligence (AI) technologies have an enormous potential to overcome accelerated data growth, complexity, and heterogeneity within and across data sources. Our review focuses on the recent progress in integrative proteomic profiling strategies and their usage in combination with machine learning and deep learning technologies for the discovery of novel biomarker candidates for HCC early diagnosis and prognosis. We discuss conventional and promising proteomic biomarkers of HCC such as AFP, lens culinaris agglutinin (LCA)-reactive L3 glycoform of AFP (AFP-L3), des-gamma-carboxyprothrombin (DCP), osteopontin (OPN), glypican-3 (GPC3), dickkopf-1 (DKK1), midkine (MDK), and squamous cell carcinoma antigen (SCCA) and highlight their functional significance including the involvement in cell signaling such as Wnt/β-catenin, PI3K/Akt, integrin αvβ3/NF-κB/HIF-1α, JAK/STAT3 and MAPK/ERK-mediated pathways dysregulated in HCC. We show that currently available computational platforms for big data analysis and AI technologies can both enhance proteomic profiling and improve imaging techniques to enhance the translational application of proteomics data into precision medicine.
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Affiliation(s)
- Nurbubu T. Moldogazieva
- Laboratory of Bioinformatics, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
- Correspondence: or
| | - Innokenty M. Mokhosoev
- Department of Biochemistry and Molecular Biology, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia; (I.M.M.); (A.A.T.)
| | - Sergey P. Zavadskiy
- Department of Pharmacology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia;
| | - Alexander A. Terentiev
- Department of Biochemistry and Molecular Biology, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia; (I.M.M.); (A.A.T.)
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