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Ikeda Y, Kondo M, Suehiro JI, Oshima H, Kok SY, Takahashi K, Pauty J, Wang D, Sakurai H, Watabe T, Oshima M, Matsunaga YT. A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation. iScience 2025; 28:112517. [PMID: 40491477 PMCID: PMC12146038 DOI: 10.1016/j.isci.2025.112517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 01/08/2025] [Accepted: 04/18/2025] [Indexed: 06/11/2025] Open
Abstract
Circulating tumor cell (CTC) clusters are often detected in blood samples of patients with high-grade tumor and are associated with tumor metastasis and poor prognosis. However, the underlying mechanisms by which cancer cell clusters are released from primary tumors beyond blood vessel barriers remain unclear. In this study, a three-dimensional (3D) in vitro culture system was developed to visualize tumor intravasation by positioning tumor organoids with distinct genetic backgrounds to surround microvessels. We visualized tumor intravasation in a cluster unit, including collective migration toward microvessels, vessel co-option, and the release of CTC clusters-an invasion mechanism not previously reported. Furthermore, elevated levels of transforming growth factor β (TGF-β) and activin expression in endothelial cells within the coculture microenvironment were pivotal for facilitating tumor cell intravasation, which was associated with endothelial-to-mesenchymal transition (EndoMT) in microvessels. Our 3D in vitro system can be used to develop therapeutic strategies for tumor metastasis by targeting the release of CTC clusters.
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Affiliation(s)
- Yukinori Ikeda
- Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
- Department of Bioengineering, School of Engineering, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
| | - Makoto Kondo
- Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
- Department of Bioengineering, School of Engineering, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
| | - Jun-ichi Suehiro
- Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, Japan
| | - Hiroko Oshima
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
| | - Sau Yee Kok
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
| | - Kazuki Takahashi
- Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
- Department of Biochemistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan
| | - Joris Pauty
- Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
| | - Dong Wang
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
- WPI Nano Life Science Institute, Kanazawa University, Kanazawa 920-1192, Japan
| | - Hiroyuki Sakurai
- Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, Japan
| | - Tetsuro Watabe
- Department of Biochemistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan
| | - Masanobu Oshima
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
- WPI Nano Life Science Institute, Kanazawa University, Kanazawa 920-1192, Japan
| | - Yukiko T. Matsunaga
- Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
- Department of Bioengineering, School of Engineering, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
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Baglamis S, Sheraton VM, van Neerven SM, Logiantara A, Nijman LE, Hageman LA, Léveillé N, Elbers CC, Bijlsma MF, Vermeulen L, Krawczyk PM, Lenos KJ. Clonal dispersal is associated with tumor heterogeneity and poor prognosis in colorectal cancer. iScience 2025; 28:112403. [PMID: 40330878 PMCID: PMC12051713 DOI: 10.1016/j.isci.2025.112403] [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: 10/10/2024] [Revised: 01/27/2025] [Accepted: 04/07/2025] [Indexed: 05/08/2025] Open
Abstract
Clonal dispersal, resulting from the intermingling of tumor cell subpopulations, is thought to be a key driver of tumor heterogeneity. Despite advances in spatial modeling of cancer biology, quantification of clonal dispersal has been challenging. This study introduces a straightforward method, relying on fluorescent cell barcoding, to quantify clonal dispersal in various in vitro and in vivo models of colorectal cancer (CRC). Our approach allows for precise localization of clones and uncovering the degree of clonal mixing across different CRC models. Our findings suggest that clonal dispersal is correlated with the expression of genes involved in epithelial-mesenchymal transition and CMS4-related signaling pathways. We further identify a dispersal gene signature, associated with intratumor heterogeneity, which is a robust clinical predictor of poor prognosis and recurrence in CRC, highlighting its potential as a prognostic marker and a putative direction for therapeutic targeting.
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Affiliation(s)
- Selami Baglamis
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Vivek M. Sheraton
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
- University of Amsterdam, Informatics Institute, Computational Science Lab, 1090 GH Amsterdam, the Netherlands
| | - Sanne M. van Neerven
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
- University of Cambridge, Wellcome Trust–Cancer Research UK Gurdon Institute, Cambridge CB2 1QN, UK
| | - Adrian Logiantara
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Lisanne E. Nijman
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Laura A. Hageman
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
| | - Nicolas Léveillé
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Clara C. Elbers
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Maarten F. Bijlsma
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Louis Vermeulen
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
- Genentech, Department of Discovery Oncology, South San Francisco, CA 94080, USA
| | - Przemek M. Krawczyk
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, University of Amsterdam, Department of Medical Biology, 1105 AZ Amsterdam, the Netherlands
| | - Kristiaan J. Lenos
- Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, 1081 BT Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Oncode Institute, Amsterdam, 3521 AL Utrecht, the Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
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Wang Y, Yue X, Lou S, Feng P, Cui B, Liu Y. Gene Swin transformer: new deep learning method for colorectal cancer prognosis using transcriptomic data. Brief Bioinform 2025; 26:bbaf275. [PMID: 40515391 PMCID: PMC12165829 DOI: 10.1093/bib/bbaf275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 04/27/2025] [Accepted: 05/19/2025] [Indexed: 06/16/2025] Open
Abstract
Transcriptome sequencing has become essential in clinical tumor research, providing in-depth insights into the biology and functionality of tumor cells. However, the vast amount of data generated and the complex relationships between gene expressions make it challenging to effectively identify clinically relevant information. In this study, we developed a method called Gene Swin Transformer to address these challenges. This approach converts transcriptomic data into Synthetic Image Elements (SIEs). We utilized data from 12 datasets, including GSE17536-GSE103479 datasets (n = 1771) and The Cancer Genome Atlas (n = 459), to generate SIEs. These elements were then classified based on survival time using deep learning algorithms to predict colorectal cancer prognosis and build a reliable prognostic model. We trained and evaluated four deep learning models-BeiT, ResNet, Swin Transformer, and ViT Transformer-and compared their performance. The enhanced Swin-T model outperformed the other models, achieving weighted precision, recall, and F1 scores of 0.708, 0.692, and 0.705, respectively, along with area under the curve values of 80.2%, 72.7%, and 76.9% across three datasets. This model demonstrated the strongest prognostic prediction capabilities among those evaluated. Additionally, the PEX10 gene was identified as a key prognostic marker through both visual attention matrix analysis and bioinformatics methods. Our study demonstrates that the Gene Swin model effectively transforms Ribonucleic Acid (RNA) sequencing data into SIEs, enabling prognosis prediction through attention-based algorithms. This approach supports the development of a data-driven, unified, and automated model, offering a robust tool for classification and prediction tasks using RNA sequencing data. This advancement presents a novel clinical strategy for cancer treatment and prognosis forecasting.
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Affiliation(s)
- Yangyang Wang
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, No.150 Haping Road, Harbin, Heilongjiang 150081, China
| | - Xinyu Yue
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, No.150 Haping Road, Harbin, Heilongjiang 150081, China
| | - Shenghan Lou
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, No.150 Haping Road, Harbin, Heilongjiang 150081, China
| | - Peinan Feng
- School of Computer Science and Engineering, Northeastern University, No.195 Innovation Road, Hunnan District, Shenyang, Liaoning 110169, China
| | - Binbin Cui
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, No.150 Haping Road, Harbin, Heilongjiang 150081, China
| | - Yanlong Liu
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, No.150 Haping Road, Harbin, Heilongjiang 150081, China
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Szeto S, Kytölä S, Erkan EP, Ahtiainen M, Mecklin J, Kuopio T, Sallinen V, Lepistö A, Koskenvuo L, Renkonen‐Sinisalo L, Anttonen A, Heiskala K, Tulokas S, Mäkelä S, Wirta E, Tuunanen T, Salminen T, Ristimäki A, Seppälä TT. Performance Comparison of Droplet Digital PCR and Next-Generation Sequencing for Circulating Tumor DNA Detection in Non-Metastatic Rectal Cancer. Cancer Med 2025; 14:e70943. [PMID: 40346007 PMCID: PMC12062871 DOI: 10.1002/cam4.70943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 03/16/2025] [Accepted: 04/28/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Circulating tumor DNA (ctDNA) can potentially identify rectal cancer patients benefiting from neoadjuvant and adjuvant therapy. This study compared droplet digital PCR (ddPCR) and next-generation sequencing (NGS) for ctDNA detection in localized rectal cancer before and after surgery. METHODS Pre-therapy plasma and rectal tumor samples were collected from a development group (n = 41) and a validation group (n = 26). Mutations in tumor samples were identified using NGS, and ctDNA detection was performed with both ddPCR and NGS. Recurrence was assessed 1 year after surgery in the development group. RESULTS In the development group, ddPCR detected ctDNA in 24/41 (58.5%) and NGS panel in 15/41 (36.6%; p = 0.00075) of the baseline plasma. In the validation group, 21/26 (80.8%) patients had detectable ctDNA in the pre-therapy plasma. A positive ctDNA result was associated with higher clinical tumor stage and with lymph node positivity as detected by MRI. Postoperative ddPCR did not detect ctDNA before most recurrences. CONCLUSIONS We demonstrated a practical oligomarker ctDNA test for localized rectal cancer suitable for clinical workflow, and that ddPCR detects ctNA from pre-therapy plasma at a satisfactory level in advanced rectal cancers. Detecting ctDNA with ddPCR may help to assess the local severity, but the clinical utility of this approach should be evaluated in clinical trials.
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Affiliation(s)
- Säde Szeto
- Applied Tumor Genomics Research Program, Research Program Unit, Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
| | - Soili Kytölä
- Department of Genetics, HUS Diagnostic CenterHelsinki University HospitalHelsinkiFinland
- Department of GeneticsUniversity of HelsinkiHelsinkiFinland
| | - Erdogan Pekcan Erkan
- Applied Tumor Genomics Research Program, Research Program Unit, Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
- Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, Tampere University HospitalTampereFinland
| | - Maarit Ahtiainen
- Department of Molecular PathologyCentral Finland Hospital Nova, Wellbeing Services County of Central FinlandJyväskyläFinland
| | - Jukka‐Pekka Mecklin
- Department of Education and ScienceCentral Finland Hospital Nova, Wellbeing Services County of Central FinlandJyväskyläFinland
- Faculty of Sports and Health SciencesUniversity of JyväskyläJyväskyläFinland
| | - Teijo Kuopio
- Department of Molecular PathologyCentral Finland Hospital Nova, Wellbeing Services County of Central FinlandJyväskyläFinland
- Department of Biological and Environmental ScienceUniversity of JyväskyläJyväskyläFinland
| | - Ville Sallinen
- Department of Gastroenterological SurgeryHelsinki University Hospital and University of HelsinkiHelsinkiFinland
- Transplantation and Liver SurgeryHelsinki University Hospital and University of HelsinkiHelsinkiFinland
| | - Anna Lepistö
- Department of Gastroenterological SurgeryHelsinki University Hospital and University of HelsinkiHelsinkiFinland
| | - Laura Koskenvuo
- Department of Gastroenterological SurgeryHelsinki University Hospital and University of HelsinkiHelsinkiFinland
| | - Laura Renkonen‐Sinisalo
- Department of Gastroenterological SurgeryHelsinki University Hospital and University of HelsinkiHelsinkiFinland
| | - Anu Anttonen
- Department of OncologyHUS Comprehensive Cancer Centre and University of HelsinkiHelsinkiFinland
| | - Kukka Heiskala
- Department of OncologyHUS Comprehensive Cancer Centre and University of HelsinkiHelsinkiFinland
| | - Sanni Tulokas
- Department of OncologyHUS Comprehensive Cancer Centre and University of HelsinkiHelsinkiFinland
| | - Siru Mäkelä
- Department of OncologyHUS Comprehensive Cancer Centre and University of HelsinkiHelsinkiFinland
| | - Erkki‐Ville Wirta
- Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, Tampere University HospitalTampereFinland
- Department of Gastroenterology and Alimentary Tract SurgeryTampere University HospitalTampereFinland
| | - Tuija Tuunanen
- Department of OncologyTampere University HospitalTampereFinland
| | - Tapio Salminen
- Department of OncologyTampere University HospitalTampereFinland
| | - Ari Ristimäki
- Applied Tumor Genomics Research Program, Research Program Unit, Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
- Department of PathologyHUS Diagnostic Center, Helsinki University HospitalHelsinkiFinland
| | - Toni T. Seppälä
- Applied Tumor Genomics Research Program, Research Program Unit, Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
- Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, Tampere University HospitalTampereFinland
- Department of Gastroenterology and Alimentary Tract SurgeryTampere University HospitalTampereFinland
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5
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Esteva M, March S, Martín-Rabadan M, Torres-Solera E, Ripoll J. Health-related quality of life and lifestyle in long-term survivors of colorectal cancer and a matched non-cancer reference group. Clin Transl Oncol 2025:10.1007/s12094-025-03930-0. [PMID: 40299301 DOI: 10.1007/s12094-025-03930-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 04/06/2025] [Indexed: 04/30/2025]
Abstract
OBJECTIVE To compare the long-term health status of a group of survivors of colorectal cancer (CRC) with a reference group of individuals who did not have cancer. We determined the physical, mental, and general health-related quality of life (HRQoL); overall morbidities and CRC-specific morbidities related to the delayed effects of treatment; and maintenance of a healthy lifestyle in these two groups. METHODS This descriptive cross-sectional study was conducted from 2016 to 2019 in the Balearic Islands (Spain). CRC patients who were diagnosed from 2011 to 2012 and survived at least 5 years were randomly selected from the Majorca and Eivissa-Formentera cancer registries. The reference group consisted of individuals matched for gender and age who had no history of cancer. RESULTS We examined 201 CRC survivors and 199 matched individuals without cancer. The global analysis showed that the two groups had similar scores in the physical and mental components of the Short Form 12 (SF-12) HRQoL scale and in general health status. The CRC survivors had significantly higher prevalence of general comorbidity and CRC-specific comorbidity. Multivariate analyses and calculation of odds ratios (ORs) showed that the groups had similar physical HRQoL (Model 1, OR: 1.01, 95% CI: 0.99-1.03), mental HRQoL (Model 2, OR: 0.99, 95% CI: 0.66-1.01), and general HRQoL (Model 3, OR: 1.67, 95% CI: 0.39-1.13). However, the long-term CRC survivors had significantly greater ORs for an increased overall comorbidity index, number of CRC-specific comorbidity, and obesity in all three models (P < 0.05). CONCLUSIONS The CRC survivors and individuals without cancer had similar HRQoL, suggesting that CRC survivors do not need additional services that aim to improve HRQoL. Nonetheless, health care providers should be pro-active when caring for CRC survivors, because they are more likely to present with certain comorbidity and less likely to follow a healthy lifestyle.
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Affiliation(s)
- Magdalena Esteva
- Majorca Department of Primary Care, Unit of Research, Baleares Health Service [IbSalut], Escola Graduada 3, 07002, Palma, Majorca, Spain.
- Health Research Institute of the Balearic Islands (IdISBa), Edificio S, Hospital Son Espases, Carretera de Valldemossa, 79, 07120, Palma, Majorca, Spain.
| | - Sebastià March
- Majorca Department of Primary Care, Unit of Research, Baleares Health Service [IbSalut], Escola Graduada 3, 07002, Palma, Majorca, Spain
| | - María Martín-Rabadan
- Health Research Institute of the Balearic Islands (IdISBa), Edificio S, Hospital Son Espases, Carretera de Valldemossa, 79, 07120, Palma, Majorca, Spain
- Can Misses Healthcare Centre, Baleares Health Service [IbSalut], Corona, 20-36, 07800, Ibiza, Ibiza, Spain
| | - Elena Torres-Solera
- Majorca Department of Primary Care, Unit of Research, Baleares Health Service [IbSalut], Escola Graduada 3, 07002, Palma, Majorca, Spain
| | - Joana Ripoll
- Majorca Department of Primary Care, Unit of Research, Baleares Health Service [IbSalut], Escola Graduada 3, 07002, Palma, Majorca, Spain
- Health Research Institute of the Balearic Islands (IdISBa), Edificio S, Hospital Son Espases, Carretera de Valldemossa, 79, 07120, Palma, Majorca, Spain
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Liu Y, Xie Y, Chen Y, Duan J, Bao C, Wang J, Feng H, Wang M, Ren Y, Li P, Luo Q, Xu J, Jiang M, Men Y, Wu Y, Li J, Wang G, Lu W. A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice. Nat Commun 2025; 16:2854. [PMID: 40128211 PMCID: PMC11933685 DOI: 10.1038/s41467-025-57965-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 03/07/2025] [Indexed: 03/26/2025] Open
Abstract
Immune checkpoint blockade therapy using programmed cell death 1 (PD1) or programmed death ligand 1 (PD-L1) has made significant progress in the treatment of advanced cancers, with some patients achieving long-term remission without clinical recurrence. However, only a minority of colon cancer patients respond to the therapy. Here, we report a protease-cleavable anti-PD-L1 antibody liposome, eLipo anti-PD-L1, for enhancing colon cancer therapy. In vivo, eLipo anti-PD-L1 is cleaved by legumain at colon cancer site into pegylated anti-PD-L1 and cancer-homing doxorubicin liposome. Functional assessments show cancer-targeting, legumain-responding, tumor-penetrating, and immune-activating effects, as well as efficacy in treating colon cancer-bearing mice in vivo. Further mechanistic analysis implicates genes related to T cell differentiation and T cell receptor signaling as potential molecular mediators. Lastly, human colorectal cancer tissue evaluations verify expressions of PD-L1 and legumain, hinting a potential translatability. Our study thus suggests that eLipo anti-PD-L1 may be a feasible vector for co-delivery of immunochemotherapy for colon cancer.
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Affiliation(s)
- Yixuan Liu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Ying Xie
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Yuling Chen
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Jialun Duan
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Chunjie Bao
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Jinling Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Hexuan Feng
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Mengjie Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Yuxin Ren
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Peishan Li
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Qian Luo
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Jiarui Xu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Min Jiang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Yanchen Men
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Yang Wu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Jianwei Li
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Guiling Wang
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China
| | - Wanliang Lu
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China.
- Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China.
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Cox K, Ahmed H, Saha P, Liu WK, Aitken K, Bernard J, Bishop T, Minhas P, Papadopoulos M, Johnston F, Piggott A, Pereira E, Lui D, Afshar M. Six-Month Survivorship Prediction in Spinal Metastatic Patients by Oncologists Shows Reliable Prognostication. Global Spine J 2025; 15:961-968. [PMID: 38009792 PMCID: PMC11877491 DOI: 10.1177/21925682231218712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2023] Open
Abstract
STUDY DESIGN A retrospective analysis of oncologist-provided prognoses vs actual survival outcomes of patients referred with Metastatic spinal cord compression (MSCC) to a supra-regional multidisciplinary team (MDT). OBJECTIVES Prognostic scoring systems, such as the revised Tokuhashi, are commonly used to help guide the treatment of MSCC. However, scoring systems do not accommodate for the improved outcomes of contemporary cancer therapy. Oncologist-provided prognoses play an important role in real world rapid decision making. There is a paucity of evidence assessing the accuracy of the oncologist-provided prognosis. We conducted a retrospective study to evaluate this. METHODS Data was captured between January 2015 and December 2018. Patients were split into 2 groups: Group 1 (prognosis estimated <6 months) and Group 2 (prognosis estimated >6 months). Median overall survival (mOS) and hazard ratio for death (HR) was assessed. Receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the oncologist's prognosis. RESULTS 829 patients were included. mOS in Group 1 was 5.8 months (95% CI 4.2-7.4 m), and in Group 2 mOS was not reached. Log rank test gave a Chi2 of 131 (P < .001). Cox regression analysis revealed a HR of .30 (P < .001). Area under the ROC curve was 78%. CONCLUSIONS Oncologist-provided prognosis is accurate in this cohort of unselected, consecutive MSCC patients. It reduced reliance on scoring systems that can become outdated. Given the rapid progress in cancer treatment, the oncologist's prognostic prediction is integral in efficient and effective MSCC management to help rapidly determine surgical candidacy.
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Affiliation(s)
- Kofi Cox
- Department of Medicine, St. George’s University of London, London, UK
| | - Hassam Ahmed
- Department of Medicine, St. George’s University of London, London, UK
| | - Priyanshu Saha
- Department of Medicine, St. George’s University of London, London, UK
| | - Wing Kin Liu
- Department of Oncology, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | | | - Jason Bernard
- Department of Complex Neurosurgery, Atkinson Morley Wing, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Timothy Bishop
- Department of Complex Neurosurgery, Atkinson Morley Wing, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Pawan Minhas
- Department of Complex Neurosurgery, Atkinson Morley Wing, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Marios Papadopoulos
- Department of Complex Neurosurgery, Atkinson Morley Wing, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Francis Johnston
- Department of Complex Neurosurgery, Atkinson Morley Wing, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Alicia Piggott
- Department of Complex Neurosurgery, Atkinson Morley Wing, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Erlick Pereira
- Department of Complex Neurosurgery, Atkinson Morley Wing, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Darren Lui
- Department of Complex Neurosurgery, Atkinson Morley Wing, St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Mehran Afshar
- Department of Oncology, St. George’s University Hospitals NHS Foundation Trust, London, UK
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Khazaei Z, Goodarzi E, Momenabadi V, Asadilari F, Mirshekarpour H, Abbasi R, Naghibzadeh-Tahami A. Association between Socioeconomic Inequality and the Burden of Colon and Rectum Cancer in Asia: GLOBOCAN Sources and Methods. Asian Pac J Cancer Prev 2025; 26:647-656. [PMID: 40022713 PMCID: PMC12118043 DOI: 10.31557/apjcp.2025.26.2.647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 02/04/2025] [Indexed: 03/03/2025] Open
Abstract
INTRODUCTION Colon cancer is the third most common malignancy worldwide, which is increasing in middle-income countries. Our aim in this study was to investigate the association between socioeconomic inequality and the burden of Colon and rectum cancer in Asia. METHODS All accessible data sources from 1990 to 2019 Global Burden of Disease study were used to estimate the prevalence, mortality, and disability-adjusted life years and the burden of Colon and rectum cancer in Asia. We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). All estimates were presented as counts and age-standardized rates per 100,000 populations with uncertainty intervals (UIs). The concentration index was used to calculate inequality. RESULTS The incidence and mortality of colon and rectum cancer have been increasing in recent years. The highest incidence (49.37 per 100,000) and mortality (30.25 per 100,000) belong to Brunei. The concentration index showed that the incidence and mortality rate of colon cancer is higher in countries with a high life expectancy, education level, and Gross domestic product (GDP). The highest DALY of disease (626.12 per 100,000) and YLL (603.43 per 100,000) belonged to Brunei, and the highest YLD of disease (32.67 per 100,000) belonged to Taiwan. The results revealed that the burden of the disease, YLL, and YLD for colon cancer are concentrated more in countries with a higher human development index. CONCLUSION Considering the rising trend of colon cancer burden in Asia and given the fact that the incidence, mortality, and burden of the disease are concentrated more in countries with a higher socioeconomic status, it is essential to obtain accurate estimations in these countries and to identify the associated factors to prepare for potential changes in the burden of public health caused by the disease.
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Affiliation(s)
- Zaher Khazaei
- Department of Public Health, School of Health, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Elham Goodarzi
- Social Development and Health Promotion Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | | | - Farzaneh Asadilari
- Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| | - Hossein Mirshekarpour
- Nuclear Medicine, Department of Shafa Hospital, Kerman University of Medical Sciences and Health Services, Kerman, Iran
| | - Reza Abbasi
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences Kerman, Iran
| | - Ahmad Naghibzadeh-Tahami
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
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Qiu L, Luo W, Chen Y, Guo Z, Quan J, Chi J, Guan Y, Huang Y, Lin Y. The incidence, mortality, and survival rate of colorectal cancer in Xiamen, China, from 2011 to 2020. BMC Public Health 2025; 25:176. [PMID: 39819599 PMCID: PMC11736963 DOI: 10.1186/s12889-024-21010-w] [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: 03/11/2024] [Accepted: 12/06/2024] [Indexed: 01/19/2025] Open
Abstract
INTRODUCTION Currently, nearly one-third of newly diagnosed Colorectal cancer (CRC) cases and associated deaths worldwide are from China. Among Chinese provinces, Fujian exhibited the highest CRC mortality rate. This study aims to analyze long-term trends of CRC epidemiology in Xiamen, Fujian, China. METHODS Data were obtained from various cancer surveillance systems, including the Xiamen Cancer Register system, the Xiamen Death Register system, and the household registration system. Trends in incidence, mortality and survival rates from 2011 to 2020 were analyzed using annual percent changes (APC) and average annual percent changes (AAPC), stratified by sex and residency status. RESULTS A total of 7,406 new cases and 3,726 CRC-related deaths were reported from Xiamen. The age-standardized of incidence and mortality rates were 26.09 per 100,000 and 12.70 per 100,000, respectively. The observed 5-year survival rate was 46.65%, with an age-standardized survival of 51.24%. CRC incidence in Xiamen is significantly increasing (AAPC = 4.90%). In contrast, trends in CRC mortality and survival rates are not significant. Urban areas exhibited higher rates of CRC incidence, mortality, and survival rate compared to rural areas, though rural areas showed a more marked upward trend. CONCLUSIONS The burden of CRC in Xiamen is notably high, with a concerning increasing in incidence. This underscores the urgent need for targeted strategies to address this public health challenges.
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Affiliation(s)
- Lingxian Qiu
- Xiamen Center for Disease Control and Prevention, Xiamen City, China
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen City, China
| | - Wenting Luo
- Department of Research, The First Affiliated Hospital of Xiamen University, Xiamen, Xiamen City, China
| | - Youlan Chen
- Xiamen Center for Disease Control and Prevention, Xiamen City, China
| | - Zhinan Guo
- Xiamen Center for Disease Control and Prevention, Xiamen City, China
| | - Jiali Quan
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen City, China
| | - Jiahuang Chi
- Xiamen Center for Disease Control and Prevention, Xiamen City, China
| | - Yingying Guan
- Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen City, Fujian, China.
| | - Yue Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen City, China.
| | - Yilan Lin
- Xiamen Center for Disease Control and Prevention, Xiamen City, China.
- Xiamen Medical College, Xiamen City, China.
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Saha S, Ghosh S, Ghosh S, Nandi S, Nayak A. Unraveling the complexities of colorectal cancer and its promising therapies - An updated review. Int Immunopharmacol 2024; 143:113325. [PMID: 39405944 DOI: 10.1016/j.intimp.2024.113325] [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: 05/04/2024] [Revised: 10/01/2024] [Accepted: 10/02/2024] [Indexed: 10/30/2024]
Abstract
Colorectal cancer (CRC) continues to be a global health concern, necessitating further research into its complex biology and innovative treatment approaches. The etiology, pathogenesis, diagnosis, and treatment of colorectal cancer are summarized in this thorough review along with recent developments. The multifactorial nature of colorectal cancer is examined, including genetic predispositions, environmental factors, and lifestyle decisions. The focus is on deciphering the complex interactions between signaling pathways such as Wnt/β-catenin, MAPK, TGF-β as well as PI3K/AKT that participate in the onset, growth, and metastasis of CRC. There is a discussion of various diagnostic modalities that span from traditional colonoscopy to sophisticated molecular techniques like liquid biopsy and radiomics, emphasizing their functions in early identification, prognostication, and treatment stratification. The potential of artificial intelligence as well as machine learning algorithms in improving accuracy as well as efficiency in colorectal cancer diagnosis and management is also explored. Regarding therapy, the review provides a thorough overview of well-known treatments like radiation, chemotherapy, and surgery as well as delves into the newly-emerging areas of targeted therapies as well as immunotherapies. Immune checkpoint inhibitors as well as other molecularly targeted treatments, such as anti-epidermal growth factor receptor (anti-EGFR) as well as anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies, show promise in improving the prognosis of colorectal cancer patients, in particular, those suffering from metastatic disease. This review focuses on giving readers a thorough understanding of colorectal cancer by considering its complexities, the present status of treatment, and potential future paths for therapeutic interventions. Through unraveling the intricate web of this disease, we can develop a more tailored and effective approach to treating CRC.
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Affiliation(s)
- Sayan Saha
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Shreya Ghosh
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Suman Ghosh
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Sumit Nandi
- Department of Pharmacology, Gupta College of Technological Sciences, Asansol, West Bengal 713301, India
| | - Aditi Nayak
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India.
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Cai B, Zheng M, Li Y, Chen Z, Zhong C, Chen X, Chen G. Nomogram based on the log odds of negative lymph node/T stage can predict the prognosis of patients with colorectal cancer: a retrospective study based on SEER database and external validation in China. BMJ Open 2024; 14:e083942. [PMID: 39806584 PMCID: PMC11667382 DOI: 10.1136/bmjopen-2024-083942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 11/12/2024] [Indexed: 01/16/2025] Open
Abstract
OBJECTIVES This study investigated the prognostic role of log odds of negative lymph node/T stage (LONT) and established a nomogram based on LONT to predict the prognosis in colorectal cancer (CRC) patients. DESIGN A retrospective cohort study. SETTING AND PARTICIPANTS We enrolled 80 518 CRC patients from the Surveillance, Epidemiology and End Results database between 2010 and 2015. The dataset was split into a training cohort (56 364 patients) and a validation cohort (24 154 patients) at a ratio of 7:3. Furthermore, 500 CRC patients who underwent surgery in the Tenth Affiliated Hospital of Southern Medical University between 1 January 2017 and 20 December 2018, were recruited as the external validation set. OUTCOME MEASURES 1-, 3- and 5-year cancer-specific survival (CSS). METHODS The univariate and multivariate Cox regression analyses were carried out to identify the significant independent prognostic factors of CSS. A nomogram was established based on LONT to predict the prognosis. The performance of the nomogram was comprehensively assessed via the time-dependent receiver operating characteristic curve, concordance index (C-index), calibration curve and decision curve analysis (DCA) comprehensively. Moreover, Kaplan-Meier curves were performed to assess the CSS of the three risk subgroups. RESULT LONT was a significant independent prognostic factor for CSS (LONT1 vs LONT2, HR=0.670, 95% CI 0.642 to 0.698, p<0.001; LONT1 vs LONT3, HR=0.443, 95% CI 0.420 to 0.467, p<0.001). LONT, age, sex, race, subsite, differentiation, histology, tumour size, T stage, N stage, M stage and chemotherapy were included in the nomogram. The 1-, 3- and 5-year survival area under the curve were 0.856, 0.862 and 0.852, respectively. The C-index of the model was 0.809 (95% CI 0.825 to 0.839) in the model. The calibration curve and DCA verified the favourable predictive performance and clinical application of the nomogram. CONCLUSION CRC patients with a high LONT had a low incidence of CSS. The nomogram based on LONT could effectively predict the CSS of CRC.
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Affiliation(s)
- Boyong Cai
- Department of Gastroenterology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China
| | - Mengli Zheng
- Department of Gastroenterology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China
| | - Yimin Li
- Department of Gastroenterology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China
| | - Zhicao Chen
- Department of Gastroenterology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China
| | - Canxin Zhong
- Department of Gastroenterology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China
| | - Xiaochun Chen
- Department of Gastroenterology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China
| | - Guiquan Chen
- Department of Gastroenterology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China
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12
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Tan Z, Jiang L, Lu A, He X, Zuo Y, Yang J. Living with a permanent ostomy: a descriptive phenomenological study on postsurgical experiences in patients with colorectal cancer. BMJ Open 2024; 14:e087959. [PMID: 39532360 PMCID: PMC11574432 DOI: 10.1136/bmjopen-2024-087959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024] Open
Abstract
OBJECTIVES To explore the postsurgery lived experiences of patients with colorectal cancer with a permanent ostomy for informing initiatives to improve patient care and future quantitative research. DESIGN A descriptive qualitative phenomenological study. SETTING We conducted this study in the Colorectal Cancer Division at the Cancer Center of West China Hospital, Sichuan University, a premier institution renowned for its comprehensive cancer care and research. PARTICIPANTS 12 patients who had undergone surgeries for colorectal cancer with a permanent ostomy. RESULTS Our interviews revealed profound adjustments in the lives of colorectal cancer survivors living with permanent ostomies. Participants articulated a transition to a 'new normal', characterised by extensive daily life adjustments, psychological adaptation and ongoing management challenges. Key themes identified included the adaptation to a reshaped daily routine and altered perceptions of quality of life. Many faced substantial challenges in stoma care, requiring significant learning and adaptation. Psychological adaptations were marked by a redefinition of body autonomy and personal identity, alongside a recalibration of social interactions and privacy. The need for robust professional guidance and a comprehensive social support system was universally emphasised. CONCLUSIONS Patients with colorectal cancer with permanent ostomies navigate significant changes in their lives postsurgery, undertaking a complex process of reconstructing and adapting to a new normalcy. They recalibrate their physical, psychological and social well-being, demonstrating resilience and adaptability in the face of these challenges. Their pervasive expression of needs for information and support may reflect gaps in the existing patient education and support measures and communication strategies. Healthcare professionals and policy-makers should adopt a patient-centred approach acknowledging the multifaceted nature of postsurgery recovery and adaptation by fostering open communication, tailoring personalised education and facilitating supportive community networks.
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Affiliation(s)
- Zuo Tan
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lili Jiang
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Anqing Lu
- Department of Central Transportation, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Xiao He
- West China Medical Simulation Center, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yan Zuo
- West China School of Nursing, Sichuan University, Sichuan, China/Department of Gynecology and Obstetrics Nursing, West China Second University Hospital, Sichuan University/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, China, Chengdu, Sichuan, China
| | - Jie Yang
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Kołodziejski K, Masiewicz E, Alamri A, Zampetoulas V, Samuel L, Murray G, Lurie DJ, Broche LM, Kruk D. Markers of low field NMR relaxation features of tissues. Sci Rep 2024; 14:24901. [PMID: 39438494 PMCID: PMC11496659 DOI: 10.1038/s41598-024-74055-7] [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: 01/30/2024] [Accepted: 09/23/2024] [Indexed: 10/25/2024] Open
Abstract
This work presents an approach to exploiting Nuclear Magnetic Resonance (NMR) relaxometry data (1H spin-lattice relaxation rates covering the frequency range from below 1 kHz to 10 MHz) for the purpose of differentiating between pathological and reference tissues. Characteristic quantities (markers) that can be obtained in a straightforward manner, not resorting to an advanced analysis of 1H spin-lattice relaxation data, have been identified and compared for pathological and reference colon tissues. Moreover, the relaxation data have been parametrised in terms of Lorentzian spectral densities and the possibility of using the obtained dipolar relaxation constants and correlation times as biomarkers to assess the state of tissues has been discussed. It has also been demonstrated that the relaxation data for the reference and the pathological tissues can be attributed to two groups (for each case). The studies are a step towards exploiting the potential of NMR relaxometry for characterisation of pathological changes in tissues.
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Affiliation(s)
- Karol Kołodziejski
- Department of Physics and Biophysics, University of Warmia & Mazury in Olsztyn, Oczapowskiego 4, 10-719, Olsztyn, Poland
| | - Elzbieta Masiewicz
- Department of Physics and Biophysics, University of Warmia & Mazury in Olsztyn, Oczapowskiego 4, 10-719, Olsztyn, Poland
| | - Amnah Alamri
- School of Medicine, Medical Sciences and Nutrition, Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
- Department of Radiologic Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Vasileios Zampetoulas
- School of Medicine, Medical Sciences and Nutrition, Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - Leslie Samuel
- School of Medicine, Medical Sciences and Nutrition, Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
- Department of Oncology, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Graeme Murray
- School of Medicine, Medical Sciences and Nutrition, Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - David J Lurie
- School of Medicine, Medical Sciences and Nutrition, Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - Lionel M Broche
- School of Medicine, Medical Sciences and Nutrition, Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
| | - Danuta Kruk
- Department of Physics and Biophysics, University of Warmia & Mazury in Olsztyn, Oczapowskiego 4, 10-719, Olsztyn, Poland
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Hu ZX, Li Y, Yang X, Li YX, He YY, Niu XH, Nie TT, Guo XF, Yuan ZL. Constructing a nomogram to predict overall survival of colon cancer based on computed tomography characteristics and clinicopathological factors. World J Gastrointest Oncol 2024; 16:4104-4114. [DOI: 10.4251/wjgo.v16.i10.4104] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 08/18/2024] [Accepted: 09/06/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND The colon cancer prognosis is influenced by multiple factors, including clinical, pathological, and non-biological factors. However, only a few studies have focused on computed tomography (CT) imaging features. Therefore, this study aims to predict the prognosis of patients with colon cancer by combining CT imaging features with clinical and pathological characteristics, and establishes a nomogram to provide critical guidance for the individualized treatment.
AIM To establish and validate a nomogram to predict the overall survival (OS) of patients with colon cancer.
METHODS A retrospective analysis was conducted on the survival data of 249 patients with colon cancer confirmed by surgical pathology between January 2017 and December 2021. The patients were randomly divided into training and testing groups at a 1:1 ratio. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors associated with OS, and a nomogram model was constructed for the training group. Survival curves were calculated using the Kaplan–Meier method. The concordance index (C-index) and calibration curve were used to evaluate the nomogram model in the training and testing groups.
RESULTS Multivariate logistic regression analysis revealed that lymph node metastasis on CT, perineural invasion, and tumor classification were independent prognostic factors. A nomogram incorporating these variables was constructed, and the C-index of the training and testing groups was 0.804 and 0.692, respectively. The calibration curves demonstrated good consistency between the actual values and predicted probabilities of OS.
CONCLUSION A nomogram combining CT imaging characteristics and clinicopathological factors exhibited good discrimination and reliability. It can aid clinicians in risk stratification and postoperative monitoring and provide important guidance for the individualized treatment of patients with colon cancer.
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Affiliation(s)
- Zhe-Xing Hu
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Yin Li
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Xuan Yang
- Department of Radiology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China
| | - Yu-Xia Li
- College of Informatics, Huazhong Agriculture University, Wuhan 430070, Hubei Province, China
| | - Yao-Yao He
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Xiao-Hui Niu
- College of Informatics, Huazhong Agriculture University, Wuhan 430070, Hubei Province, China
| | - Ting-Ting Nie
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Xiao-Fang Guo
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Zi-Long Yuan
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
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15
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Boman S, Hed Myrberg I, Bruze G, Martling A, Nordenvall C, Nilsson P. Earnings and work loss after colon and rectal cancer: a Swedish nationwide matched cohort study. EClinicalMedicine 2024; 75:102770. [PMID: 39210942 PMCID: PMC11359760 DOI: 10.1016/j.eclinm.2024.102770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 07/17/2024] [Accepted: 07/17/2024] [Indexed: 09/04/2024] Open
Abstract
Background Colorectal cancer is common and prognosis is improving. The conditions of survivors of treatment, including financial consequences, are thus important. The aim of this study was to quantify loss of earnings and work loss in working-age patients with colon and rectal cancer relative to matched comparators. Methods The study utilised data from the CRCBaSe database that is generated from the nationwide Swedish ColoRectal Cancer Register and includes data from several Swedish nationwide registers. The study period was 1995-2020 for rectal cancer patients and 2007-2020 for colon cancer patients. A retrospective population-based nationwide cohort study on earnings, disposable income, and work loss, in survivors of stage I-III colorectal cancer treatment was undertaken. Median regression was used to analyse earnings and disposable income, and logistic regression to analyse the probability of work loss. Findings A cohort of 8863 colorectal cancer survivors diagnosed before 2017 and 52,514 comparators matched on birth year, legal sex, and county of residence, was analysed. There was a clear reduction in earnings between the calendar year prior to and the calendar year after diagnosis, from € 31,319 to € 23,924 for colon cancer patients and from € 32,636 to € 22,647 for rectal cancer patients, and earnings never fully recovered during the 5-year follow-up. Disposable income was practically unaltered. The probability of work loss increased in the calendar year of diagnosis, from 29.8% to 25.3% the previous year to 83.3% and 84.4% for colon and rectal cancer patients respectively, and never fully recovered. The probability of work loss was similar between colon and rectal cancer survivors, but was higher among patients with rectal cancer who had received neoadjuvant therapy. Interpretation This study shows that despite an extensive welfare system providing maintained disposable income, there is a financial burden in the form of increased risk of work loss and a reduction in earnings among survivors of colorectal cancer. Funding The study was supported by the Swedish Cancer Society, the Swedish Cancer and Allergy Foundation, and the Stockholm Cancer Society, and supported by grants provided by the Regional Agreement on Medical Training and Clinical Research (ALF) between the Stockholm County Council and Karolinska Institutet.
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Affiliation(s)
- S.E. Boman
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - I. Hed Myrberg
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - G. Bruze
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - A. Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Colorectal Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - C. Nordenvall
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Colorectal Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - P.J. Nilsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Colorectal Surgery, Karolinska University Hospital, Stockholm, Sweden
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16
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Kovacs Z, Banias L, Osvath E, Gurzu S. Synergistic Impact of ARSB, TP53, and Maspin Gene Expressions on Survival Outcomes in Colorectal Cancer: A Comprehensive Clinicopathological Analysis. APPLIED SCIENCES 2024; 14:5721. [DOI: 10.3390/app14135721] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
(1) Background: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality worldwide, with its prognosis influenced by genetic and clinicopathological factors. This study investigates the associations between the gene expressions of Arylsulfatase B (ARSB), TP53, and Maspin, alongside traditional clinicopathological features, and their impact on CRC survival outcomes. (2) Methods: 70 consecutive CRC cases were analyzed for ARSB, TP53, and Maspin gene expression using RT-qPCR, and their protein levels were assessed through immunohistochemistry. Clinicopathological parameters—age, gender, tumor localization, macroscopic and microscopic aspects, lymph node ratio, pT stage, and tumor budding—were evaluated for their prognostic significance. Kaplan–Meier survival analysis with Cox proportional hazards regression was used to determine their impact on overall survival. (3) Results: No significant survival differences were observed based on age, gender, tumor localization, and macroscopic aspect. The microscopic aspect and pT stage showed significant associations with survival, with poorer outcomes in G3 and pT3/pT4 stages, respectively. Immunohistochemical positivity for ARSB and Maspin indicated a longer survival, while TP53 protein expression alone did not significantly impact the prognosis. Dual high gene expression (ARSB + TP53, TP53 + Maspin) and triple high gene expression (ARSB + TP53 + Maspin) were significantly associated with better survival outcomes. (4) Conclusions: The combined gene expression profile of ARSB, TP53, and Maspin presents a novel prognostic marker in CRC, offering insights into the molecular dynamics of cancer cells and potential therapeutic targets. These findings emphasize the importance of integrating molecular markers with traditional clinicopathological factors for a more accurate prognostication and personalized treatment approach in CRC.
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Affiliation(s)
- Zsolt Kovacs
- Department of Biochemistry and Environmental Chmistry, University of Medicine, Pharmacy, Sciences and Technology “George Emil Palade”, 530149 Targu Mures, Romania
- Oncopathology and Translational Medicine Research Center, 530149 Targu Mures, Romania
| | - Laura Banias
- Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology “George Emil Palade”, 530149 Targu Mures, Romania
| | - Eva Osvath
- Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology “George Emil Palade”, 530149 Targu Mures, Romania
- Department of Oncology, Clinical County Hospital, 540139 Targu Mures, Romania
| | - Simona Gurzu
- Oncopathology and Translational Medicine Research Center, 530149 Targu Mures, Romania
- Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology “George Emil Palade”, 530149 Targu Mures, Romania
- Romanian Academy of Medical Sciences, 030173 Bucharest, Romania
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17
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Zhuang Y, Ai Y, Li P, Yue X, Li Y, Shan L, Wang T, Zhao P, Jin X. Amplifying colorectal cancer progression: impact of a PDIA4/SP1 positive feedback loop by circPDIA4 sponging miR-9-5p. Cancer Biol Med 2024; 21:j.issn.2095-3941.2024.0112. [PMID: 38907517 PMCID: PMC11523275 DOI: 10.20892/j.issn.2095-3941.2024.0112] [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: 03/27/2024] [Accepted: 04/29/2024] [Indexed: 06/24/2024] Open
Abstract
OBJECTIVE Colorectal cancer (CRC) is a prevalent malignant tumor with a high fatality rate. CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator. Nevertheless, the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied. METHODS Western blot, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression. The CCK-8 assay was used to assess cell growth. The Transwell assay was used to detect invasion and migration of cells. The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4 (or SP1) bind to one another. An in vivo assay was used to measure tumor growth. RESULTS It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues. CircPDIA4 knockdown prevented the invasion, migration, and proliferation of cells in CRC. Additionally, the combination of circPDIA4 and miR-9-5p was confirmed, as well as miR-9-5p binding to SP1. Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC. In addition, SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription. CircPDIA4 was shown to facilitate tumor growth in an in vivo assay. CONCLUSIONS The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression. This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.
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Affiliation(s)
- Yan Zhuang
- Department of Colorectal Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 300060, China
| | - Yiding Ai
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 300060, China
| | - Peng Li
- Department of Neurosurgery and Neuro-Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 300060, China
| | - Xin Yue
- Department of Colorectal Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 300060, China
| | - Yue Li
- Department of Gastro Colorectal Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin 300308, China
| | - Luling Shan
- Department of Gastro Colorectal Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin 300308, China
| | - Tongtong Wang
- Department of Gastro Colorectal Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin 300308, China
| | - Peng Zhao
- Department of Gastro Colorectal Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin 300308, China
| | - Xun Jin
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 300060, China
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18
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Yavuz R, Aras O, Çiyiltepe H, Çakır T, Ensari CÖ, Gömceli İ. Effect of Robotic Inferior Mesenteric Artery Ligation Level on Low Anterior Resection Syndrome in Rectum Cancer. J Laparoendosc Adv Surg Tech A 2024; 34:387-392. [PMID: 38574307 DOI: 10.1089/lap.2023.0472] [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] [Indexed: 04/06/2024] Open
Abstract
Background: Life expectancy of patients with rectal cancer is increasing day by day with innovative treatments. Low anterior resection syndrome (LARS), which disrupts the comfort of life in these patients, has become a serious problem. We aimed to evaluate the effect of high ligation (HL) and low ligation (LL) techniques on LARS in rectal cancer surgery performed with the robotic method. Materials and Methods: The data of patients diagnosed with mid-distal rectal cancer between 2016 and 2021 who underwent robotic low anterior resection by the same team in the same center with neoadjuvant chemoradiotherapy were retrospectively evaluated. Patients were divided into two groups as those who underwent HL and LL procedures. Preoperative, 8 weeks after neoadjuvant treatment, 3 and 12 months after ileostomy closure were evaluated. Results: A total of 84 patients (41 HL, 43 LL) were included in the study. There was no statistically significant difference between the demographic characteristics and pathology data of the patients. Although there was a decrease in LARS scores after neoadjuvant treatment, there was a statistically significant difference between the two groups at 3 and 12 months after ileostomy closure (P: .001, P: .015). Conclusions: In patients who underwent robotic low anterior resection, there is a statistically significant difference in the LARS score in the first 1 year with the LL technique compared with that of the HL technique, and the LL technique has superiority in reducing the development of LARS between the two oncologically indistinguishable methods.
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Affiliation(s)
- Rıdvan Yavuz
- Antalya Training and Research Hospital, Gastroenterology Surgery Department, Antalya, Turkey
| | - Orhan Aras
- Antalya Training and Research Hospital, Gastroenterology Surgery Department, Antalya, Turkey
| | - Hüseyin Çiyiltepe
- Antalya Training and Research Hospital, Gastroenterology Surgery Department, Antalya, Turkey
| | - Tebessüm Çakır
- Antalya Training and Research Hospital, Gastroenterology Surgery Department, Antalya, Turkey
| | - Cemal Özben Ensari
- Antalya Training and Research Hospital, Gastroenterology Surgery Department, Antalya, Turkey
| | - İsmail Gömceli
- Antalya Bilim University, Vocational School of Health Services, Antalya, Turkey
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Xie Y, Li J, Tao Q, Wu Y, Liu Z, Zeng C, Chen Y. Identification of glutamine metabolism-related gene signature to predict colorectal cancer prognosis. J Cancer 2024; 15:3199-3214. [PMID: 38706895 PMCID: PMC11064262 DOI: 10.7150/jca.91687] [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: 10/30/2023] [Accepted: 03/16/2024] [Indexed: 05/07/2024] Open
Abstract
Backgrounds: Colorectal cancer (CRC) is a highly malignant gastrointestinal malignancy with a poor prognosis, which imposes a significant burden on patients and healthcare providers globally. Previous studies have established that genes related to glutamine metabolism play a crucial role in the development of CRC. However, no studies have yet explored the prognostic significance of these genes in CRC. Methods: CRC patient data were downloaded from The Cancer Genome Atlas (TCGA), while glutamine metabolism-related genes were obtained from the Molecular Signatures Database (MSigDB) database. Univariate COX regression analysis and LASSO Cox regression were utilized to identify 15 glutamine metabolism-related genes associated with CRC prognosis. The risk scores were calculated and stratified into high-risk and low-risk groups based on the median risk score. The model's efficacy was assessed using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve analysis. Cox regression analysis was employed to determine the risk score as an independent prognostic factor for CRC. Differential immune cell infiltration between the high-risk and low-risk groups was assessed using the ssGSEA method. The clinical applicability of the model was validated by constructing nomograms based on age, gender, clinical staging, and risk scores. Immunohistochemistry (IHC) was used to detect the expression levels of core genes. Results: We identified 15 genes related to glutamine metabolism in CRC: NLGN1, RIMKLB, UCN, CALB1, SYT4, WNT3A, NRCAM, LRFN4, PHGDH, GRM1, CBLN1, NRG1, GLYATL1, CBLN2, and VWC2. Compared to the high-risk group, the low-risk group demonstrated longer overall survival (OS) for CRC. Clinical correlation analysis revealed a positive correlation between the risk score and the clinical stage and TNM stage of CRC. Immune correlation analysis indicated a predominance of Th2 cells in the low-risk group. The nomogram exhibited excellent discriminatory ability for OS in CRC. Immunohistochemistry revealed that the core gene CBLN1 was expressed at a lower level in CRC, while GLYATL1 was expressed at a higher level. Conclusions: In summary, we have successfully identified and comprehensively analyzed a gene signature associated with glutamine metabolism in CRC for the first time. This gene signature consistently and reliably predicts the prognosis of CRC patients, indicating its potential as a metabolic target for individuals with CRC.
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Affiliation(s)
- Yang Xie
- Department of Gastroenterology, digestive disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang China
| | - Jun Li
- Department of Gastroenterology, digestive disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang China
| | - Qing Tao
- Department of Gastroenterology, digestive disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang China
| | - Yonghui Wu
- Department of Gastroenterology, digestive disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang China
| | - Zide Liu
- Department of Gastroenterology, digestive disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang China
| | - Chunyan Zeng
- Department of Gastroenterology, digestive disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi, China
| | - Youxiang Chen
- Department of Gastroenterology, digestive disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi, China
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20
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Xu Y, Lv Y, Zhu Z, Chen Y, Zhou P, Ye L, Tang W, Xu J. Precision medicine in the treatment of colorectal cancer with liver metastases. Cancer Biol Med 2024; 20:j.issn.2095-3941.2023.0483. [PMID: 38318852 PMCID: PMC10845938 DOI: 10.20892/j.issn.2095-3941.2023.0483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 12/27/2023] [Indexed: 02/07/2024] Open
Affiliation(s)
- Yuqiu Xu
- Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yang Lv
- Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhehui Zhu
- Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yijiao Chen
- Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Peiwen Zhou
- Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Lechi Ye
- Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Wentao Tang
- Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jianmin Xu
- Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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21
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Bai M, Lu Y, Shi C, Yang J, Li W, Yin X, Huang C, Shen L, Xie L, Ba Y. Phase Ib study of anti-EGFR antibody (SCT200) in combination with anti-PD-1 antibody (SCT-I10A) for patients with RAS/BRAF wild-type metastatic colorectal cancer. Cancer Biol Med 2023; 21:j.issn.2095-3941.2023.0301. [PMID: 38148327 PMCID: PMC11271220 DOI: 10.20892/j.issn.2095-3941.2023.0301] [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: 08/15/2018] [Accepted: 11/22/2023] [Indexed: 12/28/2023] Open
Abstract
OBJECTIVE This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor (EGFR) antibody (SCT200) and an anti-programmed cell death 1 (PD-1) antibody (SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene (RAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (wt) metastatic colorectal cancer (mCRC). METHODS We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt mCRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate (ORR) and safety. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71% (18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events (TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt mCRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination group. CONCLUSIONS SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt mCRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting. (Registration No. NCT04229537).
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Affiliation(s)
- Ming Bai
- Department of GI Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin 300060, China
| | - Yao Lu
- Department of GI Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin 300060, China
| | - Chunmei Shi
- Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Jianwei Yang
- Fujian Provincial Cancer Hospital, Fuzhou 350014, China
| | - Wei Li
- Cancer Center, The First Hospital of Jilin University, Changchun 130021, China
| | - Xianli Yin
- Department of Medical Oncology Gastroenterology and Urology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Chenghui Huang
- Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Liangzhi Xie
- Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China
| | - Yi Ba
- Department of GI Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin 300060, China
- Department of Cancer Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100010, China
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22
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Huang JL, Liang L, Xie PE, Sun WL, Wang L, Cai ZW. Cucurbitacin B induces apoptosis in colorectal cells through reactive oxygen species generation and endoplasmic reticulum stress pathways. Exp Ther Med 2023; 26:484. [PMID: 37753296 PMCID: PMC10518646 DOI: 10.3892/etm.2023.12183] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 08/01/2023] [Indexed: 09/28/2023] Open
Abstract
Cucurbitacin B (CuB) is a member of the cucurbitacin family, which has shown potent anticancer pharmacological activity. Prolonged or severe endoplasmic reticulum stress (ERS) induces apoptosis; therefore, the present study investigated whether CuB may activate the ERS pathway to induce apoptosis. HT-29 and SW620 colorectal cancer (CRC) cells were treated with a range of concentrations of CuB for 48 h, and the viability and proliferation of cells were determined using Cell Counting Kit 8 (CCK8) and colony formation assays. Subsequently, the appropriate CuB concentration (5 µM) was selected for treatment of CRC cells for 48 h. Western blot analysis was used to measure the expression levels of ERS-related proteins, flow cytometry was used to evaluate apoptosis, the dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) production, and the relationship between ROS and ERS was determined by western blot analysis. Furthermore, flow cytometry was used to evaluate apoptosis after treatment with the ERS inhibitor 4-phenylbutyric acid, the ROS inhibitor N-acetylcysteine and following knockdown of CHOP expression. In addition, western blot analysis was performed to measure Bax and Bcl2 protein expression levels, and a CCK8 assay was performed to evaluate the viability of cells following knockdown of CHOP. Notably, CuB treatment increased apoptosis and inhibited cell proliferation in CRC cell lines, and these effects were mediated by ROS and ROS-regulated activation of the PERK and XBP1 ERS pathways. In conclusion, CuB may induce apoptosis in HT-29 and SW620 CRC cells via ROS and ERS.
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Affiliation(s)
- Jian-Lan Huang
- Department of Medical Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China
| | - Li Liang
- Department of Medical Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China
| | - Pei-En Xie
- Department of Medical Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China
| | - Wei-Liang Sun
- Department of Medical Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China
| | - Li Wang
- Department of Medical Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China
| | - Zheng-Wen Cai
- Department of Medical Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China
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23
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Wang X, Qiu W, Liu H, He M, He W, Li Z, Wu Z, Xu X, Chen P. The inducible secreting TLR5 agonist, CBLB502, enhances the anti-tumor activity of CAR133-NK92 cells in colorectal cancer. Cancer Biol Med 2023; 20:j.issn.2095-3941.2023.0033. [PMID: 37731205 PMCID: PMC10546094 DOI: 10.20892/j.issn.2095-3941.2023.0033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 07/17/2023] [Indexed: 09/22/2023] Open
Abstract
OBJECTIVE CAR-T/NK cells have had limited success in the treatment of solid tumors, such as colorectal cancer (CRC), in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative relapse after the initial response. This barrier might be overcome by enhancing the recruitment and durability of endogenous immune cells. METHODS Immunohistochemistry and flow cytometry were used to assess the expression of CD133 antigen in tissue microarrays and cell lines, respectively. Retroviral vector transduction was used to generate CBLB502-secreting CAR133-NK92 cells (CAR133-i502-NK92). The tumor killing capacity of CAR133-NK92 cells in vitro and in vivo were quantified via LDH release, the RTCA assay, and the degranulation test, as well as measuring tumor bioluminescence signal intensity in mice xenografts. RESULTS We engineered CAR133-i502-NK92 cells and demonstrated that those cells displayed enhanced proliferation (9.0 × 104 cells vs. 7.0 × 104 cells) and specific anti-tumor activities in vitro and in a xenogeneic mouse model, and were well-tolerated. Notably, CBLB502 secreted by CAR133-i502-NK92 cells effectively activated endogenous immune cells. Furthermore, in hCD133+/hCD133- mixed cancer xenograft models, CAR133-i502-NK92 cells suppressed cancer growth better than the counterparts (n = 5, P = 0.0297). Greater T-cell infiltration was associated with greater anti-tumor potency (P < 0.0001). CONCLUSIONS Armed with a CBLB502 TLR5 agonist, CAR133-NK92 cells were shown to be capable of specifically eliminating CD133-positive colon cancer cells in a CAR133-dependent manner and indirectly eradicating CD133-negative colon cancer cells in a CBLB502-specific endogenous immune response manner. This study describes a novel technique for optimizing CAR-T/NK cells for the treatment of antigenically-diverse solid tumors.
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Affiliation(s)
- Xiaohui Wang
- College of Biotechnology, Southwest University, Chongqing 400715, China
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Wei Qiu
- Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China
| | - Haoyu Liu
- College of Biotechnology, Southwest University, Chongqing 400715, China
| | - Min He
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Wei He
- College of Biotechnology, Southwest University, Chongqing 400715, China
| | - Zhan Li
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Zhiqiang Wu
- Department of Biotherapeutics, The First Medical Center, Chinese PLA General Hospital, Beijing 100038, China
| | - Xiang Xu
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Ping Chen
- College of Biotechnology, Southwest University, Chongqing 400715, China
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Yang M, Xu Z, Mi M, Ding Y, Pan Y, Yuan Y, Sun W, Weng S. CSCO guidelines for metastatic colorectal cancer: personalized medicine in clinical practice. Cancer Biol Med 2023; 20:j.issn.2095-3941.2023.0211. [PMID: 37700433 PMCID: PMC10546093 DOI: 10.20892/j.issn.2095-3941.2023.0211] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 07/21/2023] [Indexed: 09/14/2023] Open
Affiliation(s)
- Mengyuan Yang
- Department of Medical Oncology (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Ziheng Xu
- Department of Medical Oncology (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Mi Mi
- Department of Medical Oncology (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Yuwei Ding
- Department of Medical Oncology (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Yuefen Pan
- Department of Medical Oncology, Huzhou Central Hospital, Huzhou 313000, China
| | - Ying Yuan
- Department of Medical Oncology (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou 310009, China
- Cancer Center of Zhejiang University, Hangzhou 310058, China
- Binjiang Institute of Zhejiang University, Hangzhou 310052, China
| | - Weijing Sun
- Department of Medical Oncology, The University of Kansas, School of Medicine, Lawrence, KS 66045, United States
| | - Shanshan Weng
- Department of Medical Oncology (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou 310009, China
- Cancer Center of Zhejiang University, Hangzhou 310058, China
- Binjiang Institute of Zhejiang University, Hangzhou 310052, China
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Li W, Yang Z, Ding L, Wang Y, Zhao X, Chu JJ, Ji Q, Yao M, Wang J. A novel 4-(1,3,4-thiadiazole-2-ylthio)pyrimidine derivative inhibits cell proliferation by suppressing the MEK/ERK signaling pathway in colorectal cancer. ACTA PHARMACEUTICA (ZAGREB, CROATIA) 2023; 73:489-502. [PMID: 37708962 DOI: 10.2478/acph-2023-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/18/2023] [Indexed: 09/16/2023]
Abstract
Colorectal cancer (CRC) is one of the most common types of malignant cancers worldwide. Although molecularly targeted therapies have significantly improved treatment outcomes, most of these target inhibitors are resistant. Novel inhibitors as potential anticancer drug candidates are still needed to be discovered. Therefore, in the present study, we synthesized a novel 4-(1,3,4-thiadiazole-2-ylthio)pyrimidine derivative (compound 4) using fragment- and structure-based techniques and then investigated the anticancer effect and underlying mechanism of anti-CRC. The results revealed that compound 4 significantly inhibited HCT116 cell proliferation with IC 50 values of 8.04 ± 0.94 µmol L-1 after 48 h and 5.52 ± 0.42 µmol L-1 after 72 h, respectively. Compound 4 also inhibited colony formation, migration, and invasion of HCT116 cells in a dose-dependent manner, as well as inducing cell apoptosis and arresting the cell cycle in the G2/M phase. In addition, compound 4 was able to inhibit the activation of the MEK/ERK signaling in HCT116 cells. And compound 4 yielded the same effects as the MEK inhibitor U0126 on cell apoptosis and MEK/ERK-related proteins. These findings suggested that compound 4 inhi bited cell proliferation and growth, and induced cell apoptosis, indicating its use as a novel and potent anticancer agent against CRC via the MEK/ERK signaling pathway.
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Affiliation(s)
- Weiwei Li
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China
| | - Zhifu Yang
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China
| | - Likun Ding
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China
| | - Ying Wang
- Department of Pharmacy, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi Province 710032, China
| | - Xian Zhao
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China
| | - Jian Jie Chu
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China
| | - Qing Ji
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China
| | - Minna Yao
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China
| | - Jingwen Wang
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, China
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Wang GR, Xu H, Chen HZ, Chen YS, Ni ZJ, Fan LY, Zhang AH, Xu PP, Qian Y, Cai B, Chen JG. Survival of 48866 cancer patients: results from Nantong area, China. Front Oncol 2023; 13:1244545. [PMID: 37637071 PMCID: PMC10455932 DOI: 10.3389/fonc.2023.1244545] [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: 06/23/2023] [Accepted: 07/26/2023] [Indexed: 08/29/2023] Open
Abstract
Objective This study aimed to provide a realistic observation of survival by major site for 48,866 cancer patients treated at a tertiary cancer hospital in a rural area of China. Methods Patients with cancer registered between 2007 and 2017 in the Nantong rural area were followed up. The starting date for survival calculation was the date of the first diagnosis of cancer at the Nantong Tumor Hospital, and the closing date was December 31, 2020. Observed survival (OS) was analyzed according to ICD-10 site, sex, age, region, and hospitalization period using the life table method and compared using the Wilcoxon (Gehan) statistic. Results The overall 5-year OS rate was 40.48% for all 48,866 patients, 30.19% for males, and 51.90% for females. The top five cancer sites, accounting for 60.51% of the total cases, were the esophagus, lung, stomach, liver, and cervix, with 5-year OS rates of 33.72%, 18.64%, 32.10%, 19.04%, and 71.51%, respectively. The highest 5-year OS was observed in the thyroid (87.52%) and the lowest was in the pancreas (6.37%). Survival was significantly higher in younger patients than in older patients, with 5-year OSs of 69.26% and 19.84% in those aged 20-29 and 90-99 years, respectively. Five-year OSs improved significantly from 39.35% in 2007-2011 to 41.26% in 2012-2017. Conclusion Overall survival improved over the years, although the improvement at some sites was not significant. The observed survival varies from region to region, reflecting differences in the patterns of major sites, disparities in proportions of hospitalization, and demographic characteristics.
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Affiliation(s)
- Gao-Ren Wang
- Department of Epidemiology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, China
| | - Hong Xu
- Department of Chronic Disease Prevention and Control, Nantong Center for Disease Control and Prevention, Nantong, China
| | - Hai-Zhen Chen
- Department of Epidemiology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, China
| | - Yong-Sheng Chen
- Department of Epidemiology, Qidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong, China
| | - Zhuo-Jian Ni
- Department of Chronic Disease Prevention and Control, Haimen Center for Disease Control and Prevention, Haimen, China
| | - Li-Yun Fan
- Department of Chronic Disease Prevention and Control, Tongzhou Center for Disease Control and Prevention, Tongzhou, China
| | - Ai-Hong Zhang
- Department of Chronic Disease Prevention and Control, Rudong Center for Disease Control and Prevention, Rudong, China
| | - Pei-Pei Xu
- Department of Chronic Disease Prevention and Control, Rugao Center for Disease Control and Prevention, Rugao, China
| | - Yun Qian
- Department of Chronic Disease Prevention and Control, Hai’an Center for Disease Control and Prevention, Hai’an, China
| | - Bo Cai
- Department of Chronic Disease Prevention and Control, Nantong Center for Disease Control and Prevention, Nantong, China
| | - Jian-Guo Chen
- Department of Epidemiology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, China
- Department of Epidemiology, Qidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong, China
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Hui J, Zhou M, An G, Zhang H, Lu Y, Wang X, Zhao X. Regulatory role of exosomes in colorectal cancer progression and potential as biomarkers. Cancer Biol Med 2023; 20:j.issn.2095-3941.2023.0119. [PMID: 37553810 PMCID: PMC10476469 DOI: 10.20892/j.issn.2095-3941.2023.0119] [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: 04/12/2023] [Accepted: 06/29/2023] [Indexed: 08/10/2023] Open
Abstract
Colorectal cancer (CRC) remains an enormous challenge to human health worldwide. Unfortunately, the mechanism underlying CRC progression is not well understood. Mounting evidence has confirmed that exosomes play a vital role in CRC progression, which has attracted extensive attention among researchers. In addition to acting as messengers between CRC cells, exosomes also participate in the CRC immunomodulatory process and reshape immune function. As stable message carriers and liquid biopsy option under development, exosomes are promising biomarkers in the diagnosis or treatment of CRC. In this review we have described and analyzed the biogenesis and release of exosomes and current research on the role of exosomes in immune regulation and metastasis of CRC. Moreover, we have discussed candidate exosomal molecules as potential biomarkers to diagnose CRC, predict CRC progression, or determine CRC chemoresistance, and described the significance of exosomes in the immunotherapy of CRC. This review provides insight to further understand the role of exosomes in CRC progression and identify valuable biomarkers that facilitate the clinical management of CRC patients.
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Affiliation(s)
- Juan Hui
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an 710032, China
| | - Mingzhen Zhou
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an 710032, China
| | - Guangzhou An
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
- Department of Radiation Protection Medicine, Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Faculty of Preventive Medicine, Air Force Medical University, Xi’an 710032, China
| | - Hui Zhang
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
- Department of Traditional Chinese Medicine, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
| | - Yuanyuan Lu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an 710032, China
| | - Xin Wang
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xi’an 710038, China
| | - Xiaodi Zhao
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an 710032, China
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Cann CG, LaPelusa MB, Cimino SK, Eng C. Molecular and genetic targets within metastatic colorectal cancer and associated novel treatment advancements. Front Oncol 2023; 13:1176950. [PMID: 37409250 PMCID: PMC10319053 DOI: 10.3389/fonc.2023.1176950] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/30/2023] [Indexed: 07/07/2023] Open
Abstract
Colorectal cancer results in the deaths of hundreds of thousands of patients worldwide each year, with incidence expected to rise over the next two decades. In the metastatic setting, cytotoxic therapy options remain limited, which is reflected in the meager improvement of patient survival rates. Therefore, focus has turned to the identification of the mutational composition inherent to colorectal cancers and development of therapeutic targeted agents. Herein, we review the most up to date systemic treatment strategies for metastatic colorectal cancer based on the actionable molecular alterations and genetic profiles of colorectal malignancies.
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Affiliation(s)
- Christopher G. Cann
- Department of Medicine: Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Michael B. LaPelusa
- Department of Medicine: Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Sarah K. Cimino
- Department of Pharmacy, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Cathy Eng
- Department of Medicine: Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, United States
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Mo S, Ye L, Wang D, Han L, Zhou S, Wang H, Dai W, Wang Y, Luo W, Wang R, Xu Y, Cai S, Liu R, Wang Z, Cai G. Early Detection of Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Cancer via Circulating Tumor DNA Methylation. JAMA Oncol 2023; 9:770-778. [PMID: 37079312 PMCID: PMC10119774 DOI: 10.1001/jamaoncol.2023.0425] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 12/21/2022] [Indexed: 04/21/2023]
Abstract
Importance Detection of molecular residual disease and risk stratification as early as possible may improve the treatment of patients with cancer. Efficient pragmatic tests are therefore required. Objective To measure circulating tumor DNA (ctDNA) with 6 DNA methylation markers in blood samples and to evaluate the association of the presence of ctDNA with colorectal cancer (CRC) recurrence throughout the disease course. Design, Setting, and Participants In this multicenter prospective longitudinal cohort study performed from December 12, 2019, to February 28, 2022, 350 patients with stage I to III CRC were recruited from 2 hospitals for collection of blood samples before and after surgery, during and after adjuvant chemotherapy, and every 3 months for up to 2 years. A multiplex, ctDNA methylation, quantitative polymerase chain reaction assay was used to detect ctDNA in plasma samples. Results A total of 299 patients with stage I to III CRC were evaluated. Of 296 patients with preoperative samples, 232 (78.4%) tested positive for any of the 6 ctDNA methylation markers. A total of 186 patients (62.2%) were male, and the mean (SD) age was 60.1 (10.3) years. At postoperative month 1, ctDNA-positive patients were 17.5 times more likely to relapse than were ctDNA-negative patients (hazard ratio [HR], 17.5; 95% CI, 8.9-34.4; P < .001). The integration of ctDNA and carcinoembryonic antigen tests showed risk stratification for recurrence with an HR of 19.0 (95% CI, 8.9-40.7; P < .001). Furthermore, ctDNA status at postoperative month 1 was strongly associated with prognosis in patients treated with adjuvant chemotherapy of different durations and intensities. After adjuvant chemotherapy, ctDNA-positive patients had a significantly shorter recurrence-free survival than did the ctDNA-negative patients (HR, 13.8; 95% CI, 5.9-32.1; P < .001). Longitudinal ctDNA analysis after the postdefinitive treatment showed a discriminating effect in that ctDNA-positive patients had poorer recurrence-free survival than did the ctDNA-negative patients (HR, 20.6; 95% CI, 9.5-44.9; P < .001). The discriminating effect was enhanced (HR, 68.8; 95% CI, 18.4-257.7; P < .001) when ctDNA status was maintained longitudinally. Postdefinitive treatment analysis detected CRC recurrence earlier than radiologically confirmed recurrence, with a median lead time of 3.3 months (IQR, 0.5-6.5 months). Conclusions and Relevance The findings of this cohort study suggest that longitudinal assessment of ctDNA methylation may enable the early detection of recurrence, potentially optimizing risk stratification and postoperative treatment of patients with CRC.
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Affiliation(s)
- Shaobo Mo
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Li Ye
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dongyang Wang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lingyu Han
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shuang Zhou
- Singlera Genomics (Shanghai) Ltd, Shanghai, China
| | - Hui Wang
- Singlera Genomics (Shanghai) Ltd, Shanghai, China
| | - Weixing Dai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yichao Wang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wenqin Luo
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Renjie Wang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ye Xu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Rui Liu
- Singlera Genomics (Shanghai) Ltd, Shanghai, China
| | - Zheng Wang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Guoxiang Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Chen H, Yin L, Yang J, Ren N, Chen J, Lu Q, Huang Y, Feng Y, Wang W, Wang S, Liu Y, Song Y, Li Y, Jin J, Tan W, Lin D. Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy. Cancer Biol Med 2023; 20:j.issn.2095-3941.2022.0711. [PMID: 37144561 PMCID: PMC10157810 DOI: 10.20892/j.issn.2095-3941.2022.0711] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 03/06/2023] [Indexed: 05/06/2023] Open
Abstract
OBJECTIVE The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment. This study determined the effects of genetic variations in genes involved in apoptosis, pyroptosis, and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy (CRT). METHODS The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT. The associations between genetic variations and overall survival (OS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs) computed using a Cox proportional regression model. Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase (ALOX5) gene and the ALOX5 rs702365 variant. RESULTS We detected 16 genetic polymorphisms in CASP3, CASP7, TRAILR2, GSDME, CASP4, HO-1, ALOX5, GPX4, and NRF2 that were significantly associated with OS in the additive model (P < 0.05). There was a substantial cumulative effect of three genetic polymorphisms (CASP4 rs571407, ALOX5 rs2242332, and HO-1 rs17883419) on OS. Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS. We demonstrated, for the first time, that rs702365 [G] > [C] represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response. CONCLUSIONS Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.
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Affiliation(s)
- Hongxia Chen
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Luxi Yin
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jie Yang
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ningxin Ren
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jinna Chen
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qixuan Lu
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying Huang
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yanru Feng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Weihu Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shulian Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yueping Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yongwen Song
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yexiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jing Jin
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wen Tan
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dongxin Lin
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China
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Gong G, Zheng Y, Ganesan K, Xiong Q, Tsim KWK. Danggui Buxue Tang potentiates the cytotoxicity of 5-fluorouracil on colorectal adenocarcinoma cells: A signaling mediated by c-Jun N-terminal kinase. Phytother Res 2023. [PMID: 36810895 DOI: 10.1002/ptr.7782] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 01/12/2023] [Accepted: 02/02/2023] [Indexed: 02/24/2023]
Abstract
Danggui Buxue Tang (DBT) is a well-known Chinese herbal recipe often prescribed in clinical treatment for menopausal and cardiovascular symptoms. 5-Fluorouracil (5-FU) is a chemotherapy drug that treats several cancers; however, it causes severe adverse effects and multidrug resistance. Combining natural medications can reduce the side effects of 5-FU use. Hence, we aimed to determine the role of DBT in strengthening the anticancer capabilities of 5-FU in a cultured colorectal adenocarcinoma cell line (HT-29 cell) and xenograft nude mice. HT-29 cells cultured with DBT did not exhibit cytotoxicity. However, co-administration of DBT with 5-FU significantly increased apoptosis and the expression of apoptotic markers. The inhibition of proliferation induced by DBT and 5-FU was shown to be mediated by c-Jun N-terminal kinase signaling. In addition, the potentiation effect of 5-FU and DBT was demonstrated in reducing tumor size, expressions of Ki67 and CD34 in HT-29 xenograft mice. This finding suggests that DBT can work with 5-FU as a novel chemotherapeutic strategy for treating colon cancer.
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Affiliation(s)
- Guowei Gong
- Department of Bioengineering, Zunyi Medical University, Zhuhai, China.,Guangdong Key Laboratory for Functional Substances in Medicinal Edible Resources and Healthcare Products, School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou, China
| | - Yuzhong Zheng
- Guangdong Key Laboratory for Functional Substances in Medicinal Edible Resources and Healthcare Products, School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou, China
| | - Kumar Ganesan
- School of Chinese Medicine, the Hong Kong University, Hong Kong SAR, China
| | - Qingping Xiong
- Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Huai'an, China
| | - Karl Wah Keung Tsim
- Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, China
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Zhang L, Zheng J, Ismond KP, MacKay S, LeVatte M, Constable J, Alatise OI, Kingham TP, Wishart DS. Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings. Cancer Biomark 2023; 36:17-30. [PMID: 35871322 PMCID: PMC10627333 DOI: 10.3233/cbm-220034] [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] [Indexed: 01/25/2023]
Abstract
BACKGROUND African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa). OBJECTIVE To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test. METHODS Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects. RESULTS Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set. CONCLUSIONS Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa.
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Affiliation(s)
- Lun Zhang
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Jiamin Zheng
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | | | - Scott MacKay
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Marcia LeVatte
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Jeremy Constable
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Olusegun Isaac Alatise
- Department of Surgery, Obafemi Awolowo University and Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
| | - T. Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - David S. Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
- Department of Computing Science, University of Alberta, Edmonton, AB, Canada
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Ahmad A, Prakash R, Khan MS, Altwaijry N, Asghar MN, Raza SS, Khan R. Nanoparticle-Mediated PRDX2 Inhibition for Specific Targeting of CHK2-Null Colorectal Cancer. ACS Biomater Sci Eng 2022; 8:5210-5220. [PMID: 36446128 DOI: 10.1021/acsbiomaterials.2c01073] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Synthetic lethality is a pragmatic targeted cancer therapy approach in which cancer cells harboring genetic alterations are exploited for the specific killing of cancer cells. Earlier, we have established a synthetic lethal (SL) interaction between two genes that are CHK2 and PRDX2 in colorectal cancer (CRC) cells. The SL interaction between CHK2 and PRDX2 resulted in selective targeting of CHK2-defective CRC cells. N-Carbamoyl alanine (NCA) is a PRDX2 inhibitor and is a peptide-like organic compound, which degrades after oral administration in harsh gastric pH. To overcome the limitations of NCA, a chitosan-based nanocarrier was developed for the entrapment of NCA. In this study, we targeted the SL interaction between PRDX2 and CHK2 using NCA-loaded chitosan nanoparticles (NCA-Chit NPs) to selectively inhibit the CHK2-null HCT116 cells. NCA-Chit NPs were assessed for various physicochemical characterizations such as the hydrodynamic diameter (size), zeta potential, and polydispersity index using a Zetasizer. Additionally, morphological studies for the shape and size of NPs were confirmed by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Cellular uptake of NPs was confirmed using confocal microscopy, which exhibited that nanoparticles were able to internalize into the HCT116 cells. Blank Chit NPs were found to be cytocompatible as they did not exert any cytotoxic effects on hTERT, L929, and Caco-2 cells (intestinal epithelial cells). Importantly, NCA-Chit NPs were quite hemocompatible also. In the form of an NCA-chitosan nanoformulation, the efficacy was enhanced by about 8 times compared to free form of NCA towards selective killing of CHK2-null HCT116 cells as compared to HCT116 cells. The chitosan-based nanoformulation for NCA was developed to augment the efficacy of the NCA for enhanced cell death of colorectal cancer cells having CHK2 defects.
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Affiliation(s)
- Anas Ahmad
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali140306, Punjab, India
| | - Ravi Prakash
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College Hospital, Sarfarazganj, Lucknow226003, Uttar Pradesh, India
| | - Mohd Shahnawaz Khan
- Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Riyadh Province11451, Saudi Arabia
| | - Nojood Altwaijry
- Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Riyadh Province11451, Saudi Arabia
| | - Muhammad Nadeem Asghar
- Department of Medical Biology, University of Québec at Trois-Rivieres, Trois-Rivieres, QuébecG9A 5H7, Canada
| | - Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College Hospital, Sarfarazganj, Lucknow226003, Uttar Pradesh, India
| | - Rehan Khan
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali140306, Punjab, India
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HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer. Cell Death Dis 2022; 13:888. [PMID: 36270986 PMCID: PMC9587286 DOI: 10.1038/s41419-022-05335-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 10/04/2022] [Accepted: 10/10/2022] [Indexed: 11/08/2022]
Abstract
Histone deacetylase 6 (HDAC6), a member of the HDAC family, has been identified as a potential therapeutic target for tumor therapy, but the function and underlying mechanisms of HDAC6 in colon cancer are incompletely characterized. Our study showed that the infiltration ratio of M2 macrophages was increased in colon cancer tissues with high HDAC6 expression. Similarly, the knockdown of HDAC6 in colon cancer cells inhibited cocultured macrophage M2 polarization in vitro. Analysis of the antibody chip revealed that HDAC6 promoted sIL-6R release to enhance macrophage M2 polarization. Mass spectrometry and immunoprecipitation demonstrated that, mechanistically, HDAC6 interacted with transforming growth factor β-activated kinase 1 (TAK1), deacetylated TAK1 at T178 and promoted TAK1 phosphorylation. TAK1-p38 MAPK signaling could further increase the phosphorylation and activity of ADAM17, which is responsible for shedding of IL-6R. Notably, the expression of phosphorylated TAK1 was positively correlated with HDAC6 expression and macrophage M2 polarization in human colon cancer tissues. Our study revealed a new HDAC6-TAK1-ADAM17 regulatory axis that mediates sIL-6R release and macrophage polarization in colon cancer.
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Khalid MU, Laplante S, Madani A. Machines with vision for intraoperative guidance during gastrointestinal cancer surgery. Front Med (Lausanne) 2022; 9:1025382. [PMID: 36250078 PMCID: PMC9561352 DOI: 10.3389/fmed.2022.1025382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 09/15/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
| | - Simon Laplante
- Department of Surgery, University of Toronto, Toronto, ON, Canada
- Surgical Artificial Intelligence Research Academy, University Health Network, Toronto, ON, Canada
| | - Amin Madani
- Department of Surgery, University of Toronto, Toronto, ON, Canada
- Surgical Artificial Intelligence Research Academy, University Health Network, Toronto, ON, Canada
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Xu J, Sun Y, Gong D, Fan Y. Predictive Value of Geriatric Nutritional Risk Index in Patients with Colorectal Cancer: A Meta-Analysis. Nutr Cancer 2022; 75:24-32. [PMID: 36039473 DOI: 10.1080/01635581.2022.2115521] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Geriatric Nutritional Risk Index (GNRI) has been used as a predictor of adverse prognosis in patients with colorectal cancer (CRC). This meta-analysis sought to evaluate the prognostic role of GNRI in CRC patients. Two authors comprehensively searched the studies indexed in PubMed and Embase databases until March 15, 2022. Only observational studies evaluating the association between GNRI and adverse outcomes in patients with CRC were eligible. The prognostic value of GNRI was expressed by pooling the adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the low vs. high GNRI group. Eight retrospective studies enrolling 3239 CRC patients were included. When comparing the low with the high GNRI group, the pooled HR was 2.40 (95% CI 1.71-3.39) for overall survival, 1.63 (95% CI 1.35-1.96) for disease-free survival, and 1.85 (95% CI 1.21-1.83) for ≥ 2 Clavien-Dindo Grade postoperative complications, respectively. Moreover, malnutrition defined by the cutoff GNRI at 98 was associated with a reduced overall survival (HR 1.66; 95% CI 1.37-2.02). Low GNRI score may be a promising predictor of postoperative complications and long-term poor survival in Asian patients with CRC. Malnutrition defined by the GNRI can be applied to improve risk stratification of CRC.
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Affiliation(s)
- Juan Xu
- Department of Oncology, Ganyu District People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China
| | - Yimeng Sun
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Dandan Gong
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yu Fan
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
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Identification of Potential Prognostic Biomarkers Associated with Monocyte Infiltration in Lung Squamous Cell Carcinoma. BIOMED RESEARCH INTERNATIONAL 2022; 2022:6860510. [PMID: 35993054 PMCID: PMC9388304 DOI: 10.1155/2022/6860510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 05/26/2022] [Accepted: 06/22/2022] [Indexed: 11/18/2022]
Abstract
The five-year survival rate of lung squamous cell carcinoma is significantly lower than that of other cancer types. It is therefore urgent to discover novel prognosis biomarkers and therapeutic targets and understand their correction with infiltrating immune cells to improve the prognosis of patients with lung squamous cell carcinoma. In this study, we employed robust rank aggregation algorithms to overcome the shortcomings of small sizes and potential bias in each Gene Expression Omnibus dataset of lung squamous cell carcinoma and identified 513 robust differentially expressed genes including 220 upregulated and 293 downregulated genes from six microarray datasets. Functional enrichment analysis showed that these robust differentially expressed genes were obviously involved in the extracellular matrix and structure organization, epidermis development, cell adhesion molecule binding, p53 signaling pathway, and interleukin-17 signaling pathway to affect the progress of lung squamous cell carcinoma. We further identified six hub genes from 513 robust differentially expressed genes by protein-protein interaction network and 10 topological analyses. Moreover, the results of immune cell infiltration analysis from six integrated Gene Expression Omnibus datasets and our sequencing transcriptome data demonstrated that the abundance of monocytes was significantly lower in lung squamous cell carcinoma compared to controls. Immune correlation analysis and survival analysis of hub genes suggested that three hub genes, collagen alpha-1(VII) chain, mesothelin, and chordin-like protein 1, significantly correlated with tumor-infiltrating monocytes as well as may be potential prognostic biomarkers and therapy targets in lung squamous cell carcinoma. The investigation of the correlation of hub gene markers and infiltrating monocytes can also improve to well understand the molecular mechanisms of lung squamous cell carcinoma development.
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Zhang S, Wang Y, Zhang P, Ai L, Liu T. Cardiovascular Outcomes in the Patients With Colorectal Cancer: A Multi-Registry-Based Cohort Study of 197,699 Cases in the Real World. Front Cardiovasc Med 2022; 9:851833. [PMID: 35783821 PMCID: PMC9243221 DOI: 10.3389/fcvm.2022.851833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 03/17/2022] [Indexed: 11/24/2022] Open
Abstract
PURPOSE We aimed to investigate the mortality patterns and quantitatively assess the risks of cardiovascular death (CVD) in patients with colorectal cancer (CRC). We also established a competing-risk model to predict the probability of CVD for patients with CRC. PATIENTS AND METHODS Patients with CRC who diagnosed between 2007 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were included in the present study. The cumulative incidence function (CIF) was used for CVD and other causes of death, and Gray's test was used to determine the subgroup difference in CIF. The Fine-Gray proportional subdistribution hazards model was used for identifying independent risk factors for CVD. A novel competing-risk model was established to evaluate the probability of CVD for patients with CRC. The performance of the nomogram was measured by concordance index (C-index), calibration curve, decision curve analysis (DCA), and risk stratification. RESULTS After a median follow-up of 37.00 months, 79,455 deaths occurred, of whom 56,185 (70.71%) succumbed to CRC and 23,270 (29.29%) patients died due to non-CRC, among which CVD accounted for 9,702 (41.69%), being the major cause of non-cancer deaths. The 1-, 3-, and 5-year cumulative rates for CVD were 12.20, 24.25, and 30.51%, respectively. In multivariate analysis, age, race, marital status, tumor size, tumor stage, advanced stage, surgery, and chemotherapy were independent risk factors of CVD among patients with CRC. The nomogram was well calibrated and had good discriminative ability, with a c-index of 0.719 (95% CI, 0.738-0.742) in the training cohort and 0.719 (95% CI, 0.622-0.668) in the validation cohort. DCA demonstrated that nomogram produced more benefit within wide ranges of threshold probabilities for 1-, 3-, and 5-year CVD, respectively. CONCLUSION This study was the first to analyze the CIF and risk factors for CVD among CRC based on a competing-risk model. We have also built the first 1-, 3-, and 5-year competing nomogram for predicting CVD. This nomogram had excellent performance and could help clinicians to provide individualized management in clinical practice.
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Affiliation(s)
- Shilong Zhang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yan Wang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Pengfei Zhang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Luoyan Ai
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tianshu Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
- Centre for Evidence-Based Medicine, Fudan University, Shanghai, China
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Liu YJ, Han M, Li JP, Zeng SH, Ye QW, Yin ZH, Liu SL, Zou X. An Analysis Regarding the Association Between Connexins and Colorectal Cancer (CRC) Tumor Microenvironment. J Inflamm Res 2022; 15:2461-2476. [PMID: 35449599 PMCID: PMC9017696 DOI: 10.2147/jir.s361362] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 04/06/2022] [Indexed: 12/12/2022] Open
Abstract
Background Gap junctions, as one of the major ways to maintain social connections between cells, are now considered as one of the potential regulators of tumor metastasis. However, to date, studies on the relationship between gap junctions and colorectal cancer (CRC) are limited. Methods We synthesized connexins-coding gene expression data from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as MEXPRESS database, Gene Set Cancer Analysis (GSCA) database, Human Protein Atlas (HPA) database, Tumor Immune Single Cell Hub (TISCH) database, Search Tool for Retrieval of Gene Interaction Relationships (STRING), and Cytoscape software, etc., to investigate the biological mechanisms that may be involved in connexins. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of GJA4. Results We found that CRC patients can be divided into two connexin clusters and that patients in cluster C1 had shorter survival than in cluster C2. The infiltration of M1 macrophages and NK cells was lower in cluster C1, while the levels of M2 macrophages and immune checkpoints were higher, indicating an immunosuppressed state in cluster C1. In addition, the epithelial–mesenchymal transition (EMT) phenotype was significantly activated in cluster C1. We observed that GJA4 was up-regulated in colorectal cancer tissues, which was related to poor prognosis. It was mainly expressed in fibroblasts, but the expression levels in normal intestinal epithelial cells were low. Finally, we found that GJA4 was associated with M2 macrophages and may be a potential immunosuppressive factor. Conclusion We found that there is a significant correlation between abnormal connexins expression and patients’ prognosis, and connexins play an important role in stromal-tumor interactions. Connexins, especially GJA4, can help enhance our understanding of tumor microenvironment (TME) and may guide more effective immunotherapeutic strategies.
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Affiliation(s)
- Yuan-jie Liu
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Mei Han
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China
| | - Jie-pin Li
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
- Department of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, People’s Republic of China
| | - Shu-hong Zeng
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Qian-wen Ye
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Zhong-hua Yin
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Shen-lin Liu
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Xi Zou
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
- Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing, People’s Republic of China
- Correspondence: Xi Zou; Shen-lin Liu, Email ;
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