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Pan L, Zhou Y, Kuang Y, Wang C, Wang W, Hu X, Chen X. Progress of research on γδ T cells in colorectal cancer (Review). Oncol Rep 2024; 52:160. [PMID: 39364743 PMCID: PMC11478060 DOI: 10.3892/or.2024.8819] [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: 06/17/2024] [Accepted: 09/20/2024] [Indexed: 10/05/2024] Open
Abstract
Colorectal cancer (CRC) ranks as the third most prevalent malignancy and second leading cause of cancer‑related fatalities worldwide. Immunotherapy alone or in combination with chemotherapy has a favorable survival benefit for patients with CRC. Unlike αβ T cells, which are prone to drug resistance, γδ T cells do not exhibit major histocompatibility complex restriction and can target tumor cells through diverse mechanisms. Recent research has demonstrated the widespread involvement of Vδ1T, Vδ2T, and γδ T17 cells in tumorigenesis and progression. In the present review, the influence of different factors, including immune checkpoint molecules, the tumor microenvironment and microorganisms, was summarized on the antitumor/protumor effects of these cells, aiming to provide insights for the development of more efficient and less toxic immunotherapy‑based anticancer drugs.
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Affiliation(s)
- Lijuan Pan
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, P.R. China
| | - Yiru Zhou
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
| | - Yeye Kuang
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
| | - Chan Wang
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
| | - Weimin Wang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, P.R. China
| | - Xiaotong Hu
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
| | - Xiabin Chen
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, P.R. China
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Yan Y, Zhang W, Wang Y, Yi C, Yu B, Pang X, Li K, Li H, Dai Y. Crosstalk between intestinal flora and human iron metabolism: the role in metabolic syndrome-related comorbidities and its potential clinical application. Microbiol Res 2024; 282:127667. [PMID: 38442456 DOI: 10.1016/j.micres.2024.127667] [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: 11/21/2023] [Revised: 01/31/2024] [Accepted: 02/25/2024] [Indexed: 03/07/2024]
Abstract
The interaction of iron and intestinal flora, both of which play crucial roles in many physiologic processes, is involved in the development of Metabolic syndrome (MetS). MetS is a pathologic condition represented by insulin resistance, obesity, dyslipidemia, and hypertension. MetS-related comorbidities including type 2 diabetes mellitus (T2DM), obesity, metabolism-related fatty liver (MAFLD), hypertension polycystic ovary syndrome (PCOS), and so forth. In this review, we examine the interplay between intestinal flora and human iron metabolism and its underlying mechanism in the pathogenesis of MetS-related comorbidities. The composition and metabolites of intestinal flora regulate the level of human iron by modulating intestinal iron absorption, the factors associated with iron metabolism. On the other hand, the iron level also affects the abundance, composition, and metabolism of intestinal flora. The crosstalk between these factors is of significant importance in human metabolism and exerts varying degrees of influence on the manifestation and progression of MetS-related comorbidities. The findings derived from these studies can enhance our comprehension of the interplay between intestinal flora and iron metabolism, and open up novel potential therapeutic approaches toward MetS-related comorbidities.
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Affiliation(s)
- Yijing Yan
- School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Wenlan Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yulin Wang
- School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Chunmei Yi
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Bin Yu
- School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xiaoli Pang
- School of Nursing, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Kunyang Li
- School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - HuHu Li
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Yongna Dai
- School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
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Yu X, Wang L, Niu Z, Zhu L. Controversial role of γδ T cells in colorectal cancer. Am J Cancer Res 2024; 14:1482-1500. [PMID: 38726287 PMCID: PMC11076236 DOI: 10.62347/hwmb1163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 03/29/2024] [Indexed: 05/12/2024] Open
Abstract
Colorectal cancer (CRC) is the third most frequent type of cancer, and the second leading cause of cancer-related deaths worldwide. Current treatments for patients with CRC do not substantially improve the survival and quality of life of patients with advanced CRC, thus necessitating the development of new treatment strategies. The emergence of immunotherapy has revitalized the field, showing great potential in advanced CRC treatment. Owing to the ability of tumor cells to evade the immune system through major histocompatibility complex shedding and heterogeneous and low antigen spreading, only a few patients respond to immunotherapy. γδ T cells have heterogeneous structures and functions, and their key roles in immune regulation, tumor immunosurveillance, and specific primary immune responses have increasingly been recognized. γδ T cells recognize and kill CRC cells efficiently, thus inhibiting tumor progress through various mechanisms. However, γδ T cells can potentially promote tumor development and metastasis. Thus, given this dual role in prognosis, these cells can act as either a "friend" or "foe" of CRC. In this review, we explore the characteristics of γδ T cells and their functions in CRC, highlighting their application in immunotherapy.
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Affiliation(s)
- Xianzhe Yu
- Department of Medical Oncology, Cancer Center and Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan UniversityChengdu, Sichuan, The People’s Republic of China
- Department of Gastrointestinal Surgery, Chengdu Second People’s HospitalNo. 10 Qinyun Nan Street, Chengdu, Sichuan, The People’s Republic of China
| | - Leibo Wang
- Department of Surgery, Beijing Jishuitan Hospital Guizhou HospitalGuiyang, Guizhou, The People’s Republic of China
| | - Zhongxi Niu
- Department of Thoracic Surgery, The Third Medical Center of PLA General HospitalBeijing, The People’s Republic of China
| | - Lingling Zhu
- Department of Medical Oncology, Cancer Center and Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan UniversityChengdu, Sichuan, The People’s Republic of China
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Mizokami H, Okabe A, Choudhary R, Mima M, Saeda K, Fukuyo M, Rahmutulla B, Seki M, Goh BC, Kondo S, Dochi H, Moriyama-Kita M, Misawa K, Hanazawa T, Tan P, Yoshizaki T, Fullwood MJ, Kaneda A. Enhancer infestation drives tumorigenic activation of inactive B compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma. EBioMedicine 2024; 102:105057. [PMID: 38490101 PMCID: PMC10951899 DOI: 10.1016/j.ebiom.2024.105057] [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: 03/25/2023] [Revised: 02/13/2024] [Accepted: 02/28/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignant epithelial tumor endemic to Southern China and Southeast Asia. While previous studies have revealed a low frequency of gene mutations in NPC, its epigenomic aberrations are not fully elucidated apart from DNA hypermethylation. Epigenomic rewiring and enhancer dysregulation, such as enhancer hijacking due to genomic structural changes or extrachromosomal DNA, drive cancer progression. METHODS We conducted Hi-C, 4C-seq, ChIP-seq, and RNA-seq analyses to comprehensively elucidate the epigenome and interactome of NPC using C666-1 EBV(+)-NPC cell lines, NP69T immortalized nasopharyngeal epithelial cells, clinical NPC biopsy samples, and in vitro EBV infection in HK1 and NPC-TW01 EBV(-) cell lines. FINDINGS In C666-1, the EBV genome significantly interacted with inactive B compartments of host cells; the significant association of EBV-interacting regions (EBVIRs) with B compartment was confirmed using clinical NPC and in vitro EBV infection model. EBVIRs in C666-1 showed significantly higher levels of active histone modifications compared with NP69T. Aberrant activation of EBVIRs after EBV infection was validated using in vitro EBV infection models. Within the EBVIR-overlapping topologically associating domains, 14 H3K4me3(+) genes were significantly upregulated in C666-1. Target genes of EBVIRs including PLA2G4A, PTGS2 and CITED2, interacted with the enhancers activated in EBVIRs and were highly expressed in NPC, and their knockdown significantly reduced cell proliferation. INTERPRETATION The EBV genome contributes to NPC tumorigenesis through "enhancer infestation" by interacting with the inactive B compartments of the host genome and aberrantly activating enhancers. FUNDING The funds are listed in the Acknowledgements section.
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Affiliation(s)
- Harue Mizokami
- Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan; Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan
| | - Atsushi Okabe
- Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan; Health and Disease Omics Center, Chiba University, Chiba, 260-8670, Japan
| | - Ruchi Choudhary
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore
| | - Masato Mima
- Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan; Department of Otorhinolaryngology/Head and Neck Surgery, Graduate School of Medicine, Hamamatsu University School of Medicine, Shizuoka, 431-3125, Japan
| | - Kenta Saeda
- Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan; Department of Otorhinolaryngology/Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan
| | - Masaki Fukuyo
- Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan
| | - Bahityar Rahmutulla
- Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan
| | - Motoaki Seki
- Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan
| | - Boon-Cher Goh
- Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore, 117599, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD3, 16 Medical Drive, Singapore, 117600, Singapore
| | - Satoru Kondo
- Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan
| | - Hirotomo Dochi
- Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan
| | - Makiko Moriyama-Kita
- Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan
| | - Kiyoshi Misawa
- Department of Otorhinolaryngology/Head and Neck Surgery, Graduate School of Medicine, Hamamatsu University School of Medicine, Shizuoka, 431-3125, Japan
| | - Toyoyuki Hanazawa
- Department of Otorhinolaryngology/Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan
| | - Patrick Tan
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore, 169857, Singapore
| | - Tomokazu Yoshizaki
- Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan
| | - Melissa Jane Fullwood
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore; Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore, 117599, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore.
| | - Atsushi Kaneda
- Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan; Health and Disease Omics Center, Chiba University, Chiba, 260-8670, Japan.
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Tang YJ, Zhang J, Wang J, Tian RD, Zhong WW, Yao BS, Hou BY, Chen YH, He W, He YH. Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature. World J Gastrointest Surg 2024; 16:932-943. [PMID: 38577076 PMCID: PMC10989323 DOI: 10.4240/wjgs.v16.i3.932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/29/2023] [Accepted: 02/23/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 (ACVRL1) and phospholipase A2 group IVA (PLA2G4A) genes and review the available relevant literature. CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools. At the onset 6 years ago, the patient had received treatment at a local hospital for abdominal pain persisting for 7 d, under the diagnosis of diffuse peritonitis, acute gangrenous appendicitis with perforation, adhesive intestinal obstruction, and pelvic abscess. The surgical treatment included exploratory laparotomy, appendectomy, intestinal adhesiolysis, and pelvic abscess removal. The patient's condition improved and he was discharged. However, the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge. On the basis of these features and results of subsequent colonoscopy, the clinical diagnosis was established as inflammatory bowel disease (IBD). Accordingly, aminosalicylic acid, immunotherapy, and related symptomatic treatment were administered, but the symptoms of the patient did not improve significantly. Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes. ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation, respectively. This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes. Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms. CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD. Orally administered Kangfuxin liquid may have therapeutic potential.
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Affiliation(s)
- Yong-Jing Tang
- Department of Infectious Diseases, The Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Jian Zhang
- Department of Gastroenterology, Dafang County People's Hospital, Bijie 551600, Guizhou Province, China
| | - Jie Wang
- Department of Internal Medicine, Puchang Branch, Medical Community, Suiyang County People's Hospital, Zunyi 563300, Guizhou Province, China
| | - Ren-Dong Tian
- Department of Infectious Diseases, The Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Wei-Wei Zhong
- Department of Infectious Diseases, Jingmen Central Hospital, Jingmen 448000, Hubei Province, China
| | - Ben-Sheng Yao
- Department of Infectious Diseases, Dafang County People's Hospital, Bijie 551600, Guizhou Province, China
| | - Bing-Yu Hou
- Department of Gastroenterology, Dafang County People's Hospital, Bijie 551600, Guizhou Province, China
| | - Ying-Hua Chen
- Department of Infectious Diseases, The Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Wei He
- Department of Infectious Diseases, The Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Yi-Huai He
- Department of Infectious Diseases, The Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
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Lei Z, Tang R, Wu Y, Mao C, Xue W, Shen J, Yu J, Wang X, Qi X, Wei C, Xu L, Zhu J, Li Y, Zhang X, Ye C, Chen X, Yang X, Zhou S, Su C. TGF-β1 induces PD-1 expression in macrophages through SMAD3/STAT3 cooperative signaling in chronic inflammation. JCI Insight 2024; 9:e165544. [PMID: 38441961 PMCID: PMC11128204 DOI: 10.1172/jci.insight.165544] [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: 09/19/2022] [Accepted: 02/27/2024] [Indexed: 03/07/2024] Open
Abstract
Programmed cell death protein 1 (PD-1), a coinhibitory T cell checkpoint, is also expressed on macrophages in pathogen- or tumor-driven chronic inflammation. Increasing evidence underscores the importance of PD-1 on macrophages for dampening immune responses. However, the mechanism governing PD-1 expression in macrophages in chronic inflammation remains largely unknown. TGF-β1 is abundant within chronic inflammatory microenvironments. Here, based on public databases, significantly positive correlations between PDCD1 and TGFB1 gene expression were observed in most human tumors. Of note, among immune infiltrates, macrophages as the predominant infiltrate expressed higher PDCD1 and TGFBR1/TGFBR2 genes. MC38 colon cancer and Schistosoma japonicum infection were used as experimental models for chronic inflammation. PD-1hi macrophages from chronic inflammatory tissues displayed an immunoregulatory pattern and expressed a higher level of TGF-β receptors. Either TGF-β1-neutralizing antibody administration or macrophage-specific Tgfbr1 knockdown largely reduced PD-1 expression on macrophages in animal models. We further demonstrated that TGF-β1 directly induced PD-1 expression on macrophages. Mechanistically, TGF-β1-induced PD-1 expression on macrophages was dependent on SMAD3 and STAT3, which formed a complex at the Pdcd1 promoter. Collectively, our study shows that macrophages adapt to chronic inflammation through TGF-β1-triggered cooperative SMAD3/STAT3 signaling that induces PD-1 expression and modulates macrophage function.
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Affiliation(s)
- Zhigang Lei
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Rui Tang
- Department of Tropical Infectious Diseases, Naval Medical University, Shanghai, China
| | - Yu Wu
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Chenxu Mao
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Weijie Xue
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Junyao Shen
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Jiaojiao Yu
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Xiaohong Wang
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Xin Qi
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Chuan Wei
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Lei Xu
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Jifeng Zhu
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Yalin Li
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Xiujun Zhang
- Department of Liver Diseases, Institute of Hepatology, the Third People’s Hospital of Changzhou, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Chunyan Ye
- Department of Liver Diseases, Institute of Hepatology, the Third People’s Hospital of Changzhou, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Xiaojun Chen
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Xiaojun Yang
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of General Surgery, the Friendship Hospital of Ili Kazak Autonomous Prefecture, Yining, Xinjiang Uygur Autonomous Region, China
| | - Sha Zhou
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
| | - Chuan Su
- State Key Laboratory of Reproductive Medicine and Offspring Health, National Vaccine Innovation Platform of Nanjing Medical University, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
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Cho SH, Kim YM, An HJ, Kim JH, Kim NK. miR-665-Mediated Regulation of AHCYL2 and BVES Genes in Recurrent Implantation Failure. Genes (Basel) 2024; 15:244. [PMID: 38397233 PMCID: PMC10888078 DOI: 10.3390/genes15020244] [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: 01/09/2024] [Revised: 02/06/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
The primary goal of this investigation was to identify mRNA targets affected by dysregulated miRNAs in RIF. This was accomplished by comprehensively analyzing mRNA and miRNA expression profiles in two groups: female subjects with normal reproductive function (control, n = 5) and female subjects experiencing recurrent implantation failure (RIF, n = 5). We conducted transcriptome sequencing and small RNA sequencing on endometrial tissue samples from these cohorts. Subsequently, we validated a selection of intriguing findings using real-time PCR with samples from the same cohort. In total, our analysis revealed that 929 mRNAs exhibited differential expression patterns between the control and RIF patient groups. Notably, our investigation confirmed the significant involvement of dysregulated genes in the context of RIF. Furthermore, we uncovered promising correlation patterns within these mRNA/miRNA pairs. Functional categorization of these miRNA/mRNA pairs highlighted that the differentially expressed genes were predominantly associated with processes such as angiogenesis and cell adhesion. We identified new target genes that are regulated by miR-665, including Blood Vessel Epicardial Substance (BVES) and Adenosylhomocysteinase like 2 (AHCYL2). Our findings suggest that abnormal regulation of genes involved in angiogenesis and cell adhesion, including BVES and AHCYL2, contributes to the endometrial dysfunction observed in women with recurrent implantation failure (RIF) compared to healthy women.
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Affiliation(s)
- Sung Hwan Cho
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea; (S.H.C.); (H.J.A.)
- College of Medicine, Konyang University, Daejeon 35365, Republic of Korea
| | - Young Myeong Kim
- Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea;
| | - Hui Jeong An
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea; (S.H.C.); (H.J.A.)
- College of Life Science, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea
| | - Ji Hyang Kim
- Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13496, Republic of Korea
| | - Nam Keun Kim
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea; (S.H.C.); (H.J.A.)
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Azimnasab-Sorkhabi P, Soltani-Asl M, Soleiman Ekhtiyari M, Kfoury Junior JR. Landscape of unconventional γδ T cell subsets in cancer. Mol Biol Rep 2024; 51:238. [PMID: 38289417 DOI: 10.1007/s11033-024-09267-1] [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: 12/20/2023] [Accepted: 01/18/2024] [Indexed: 02/01/2024]
Abstract
T cells are broadly categorized into two groups, namely conventional and unconventional T cells. Conventional T cells are the most prevalent and well-studied subset of T cells. On the other hand, unconventional T cells exhibit diverse functions shared between innate and adaptive immune cells. During recent decades, γδ T cells have received attention for their roles in cancer immunity. These cells can detect various molecules, such as lipids and metabolites. Also, they are known for their distinctive ability to recognize and target cancer cells in the tumor microenvironment (TME). This feature of γδ T cells could provide a unique therapeutic tool to fight against cancer. Understanding the role of γδ T cells in TME is essential to prepare the groundwork to use γδ T cells for clinical purposes. Here, we provide recent knowledge regarding the role γδ T cell subsets in different cancer types.
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Affiliation(s)
- Parviz Azimnasab-Sorkhabi
- Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil.
| | - Maryam Soltani-Asl
- Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil
- The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | | | - Jose Roberto Kfoury Junior
- Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil
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9
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Huang KK, Ma H, Chong RHH, Uchihara T, Lian BSX, Zhu F, Sheng T, Srivastava S, Tay ST, Sundar R, Tan ALK, Ong X, Lee M, Ho SWT, Lesluyes T, Ashktorab H, Smoot D, Van Loo P, Chua JS, Ramnarayanan K, Lau LHS, Gotoda T, Kim HS, Ang TL, Khor C, Lee JWJ, Tsao SKK, Yang WL, Teh M, Chung H, So JBY, Yeoh KG, Tan P. Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression. Cancer Cell 2023; 41:2019-2037.e8. [PMID: 37890493 PMCID: PMC10729843 DOI: 10.1016/j.ccell.2023.10.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 08/08/2023] [Accepted: 10/06/2023] [Indexed: 10/29/2023]
Abstract
Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to transform to GC. By highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression, our results raise opportunities for GC precision prevention and interception.
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Affiliation(s)
- Kie Kyon Huang
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Haoran Ma
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Roxanne Hui Heng Chong
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Tomoyuki Uchihara
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Benedict Shi Xiang Lian
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Feng Zhu
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Taotao Sheng
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
| | - Supriya Srivastava
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Su Ting Tay
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Raghav Sundar
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Department of Haematology-Oncology, National University Health System, Singapore 119074, Singapore
| | - Angie Lay Keng Tan
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Xuewen Ong
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Minghui Lee
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Shamaine Wei Ting Ho
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
| | | | | | - Duane Smoot
- Department of Internal Medicine, Meharry Medical College, Nashville, TN, USA
| | - Peter Van Loo
- The Francis Crick Institute, London, UK; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Joy Shijia Chua
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Kalpana Ramnarayanan
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Louis Ho Shing Lau
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Hyun Soo Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Seoul, Korea
| | - Tiing Leong Ang
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore 529889, Singapore
| | - Christopher Khor
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore 169854, Singapore
| | - Jonathan Wei Jie Lee
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; iHealthtech, National University of Singapore, Singapore, Singapore; SynCTI, National University of Singapore, Singapore 117599, Singapore; Department of Gastroenterology & Hepatology, National University Hospital, Singapore 119074, Singapore
| | - Stephen Kin Kwok Tsao
- Department of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Wei Lyn Yang
- Department of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Ming Teh
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Hyunsoo Chung
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
| | - Jimmy Bok Yan So
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Division of Surgical Oncology, National University Cancer Institute of Singapore (NCIS), Singapore, Singapore.
| | - Khay Guan Yeoh
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Department of Gastroenterology & Hepatology, National University Hospital, Singapore 119074, Singapore.
| | - Patrick Tan
- Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore; Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore; Singhealth/Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Singapore 168752, Singapore.
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10
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Alzamami A. Implications of single-cell immune landscape of tumor microenvironment for the colorectal cancer diagnostics and therapy. Med Oncol 2023; 40:352. [PMID: 37950801 DOI: 10.1007/s12032-023-02226-z] [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: 09/11/2023] [Accepted: 10/18/2023] [Indexed: 11/13/2023]
Abstract
Colorectal cancer (CRC) originates from the polyps lining the colon and is among the most common types of cancer. With the increasing popularity of single-cell sequencing technologies, researchers have been able to better understand the immune landscape of colorectal cancer, by analyzing their expression and interactions in detail with the tumor microenvironment (TME) at single-cell level. Since the tumor-immune cell interactions play a critical part in the advancement as well as treatment response in colorectal cancer, the release of inhibitory factors such as T cells are important for recognizing and destroying cancer cells. Such information is vital to identify immunotherapeutic targets for cure and monitoring response to treatments. Therefore, a comprehensive single-cell studies-based overview of key immunogenic agents regulating the TME of CRC is provided in this review. Tumor-associated macrophages can promote tumor growth and resistance to treatment by releasing factors that inhibit the function of other immune cells. Additionally, colorectal cancer cells can express programmed cell death protein 1 and its ligand, which can also inhibit T-cell function. Researchers have found that certain types of immune cells, prominently T cells, natural killer, and dendritic cells, can have a positive impact on the prognosis of colorectal cancer patients. Treatments like immune checkpoint inhibitors and CAR-T therapies that help to release the inhibitory signals from the cancer cells allow the immune cells to function more effectively.
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Affiliation(s)
- Ahmad Alzamami
- Clinical Laboratory Science Department, College of Applied Medical Sciences, Shaqra University, 11961, Al-Quwayiyah, Saudi Arabia.
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11
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Lin P, Yan Y, Zhang Z, Dong Q, Yi J, Li Q, Zhang A, Kong X. The γδ T cells dual function and crosstalk with intestinal flora in treating colorectal cancer is a promising area of study. Int Immunopharmacol 2023; 123:110733. [PMID: 37579540 DOI: 10.1016/j.intimp.2023.110733] [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: 05/30/2023] [Revised: 07/24/2023] [Accepted: 07/27/2023] [Indexed: 08/16/2023]
Abstract
The occurrence of colorectal cancer (CRC) is highly prevalent and severely affects human health, with the third-greatest occurrence and the second-greatest rate of death globally. Current CRC treatments, including surgery, radiotherapy, and chemotherapy, do not significantly improve CRC patients' survival rate and quality of life, so it is essential to develop new treatment strategies. Adoptive cell therapy and other immunotherapy came into being. Currently, there has been an especially significant emphasis on γδ T cells as being the primary recipient of adoptive cell therapy. The present investigation found that γδ T cells possess the capability to trigger cytotoxicity in CRC cells, secrete cytokines, recruit immune cells for the purpose of destroying cancer cells, and inhibit the progress of CRC indirectly. Nevertheless, It is possible for γδ T cells to initiate a storm of inflammatory factors and inhibit the immune response to promote the advancement of CRC. This review demonstrates a close association between the γδ T cell initiation pathway and their close association with the intestinal flora. It has been observed that the intestinal flora performs a vital function in facilitating the stimulation and functioning of γδ T cells. The tumor-fighting effect is mainly regulated by desulphurizing Vibrio and lactic acid bacteria. In contrast, the regulation of tumor-promoting impact is closely related to Clostridia and ETBF. This review systematically combs γδ T cell dual function and their relationship to intestinal flora, which offers a conceptual framework for the γδ T cell application for CRC therapies.
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Affiliation(s)
- Peizhe Lin
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yijing Yan
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Ze Zhang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Qiutong Dong
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Jia Yi
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Qingbo Li
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Ao Zhang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xianbin Kong
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
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12
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Huang LT, Li TJ, Li ML, Luo HY, Wang YB, Wang JH. Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells. BMC Complement Med Ther 2023; 23:130. [PMID: 37095470 PMCID: PMC10123985 DOI: 10.1186/s12906-023-03944-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/29/2023] [Indexed: 04/26/2023] Open
Abstract
BACKGROUND With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide. METHODS Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes. RESULTS With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking. CONCLUSIONS The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.
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Affiliation(s)
- Le-Tian Huang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tie-Jun Li
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ming-Lin Li
- Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Han-Yong Luo
- Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Bing Wang
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Jia-He Wang
- Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
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13
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Wang G, Zhou J, Sun K, Yao H, Li Y, Yin H, Chen D, Shang B, Zhu J, Hou L, Zhang R, Liang Y. Evaluation of clinical significances and anti-tumor effects with several prognostic factors in patients with acute myeloid leukemia. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2023. [DOI: 10.1016/j.jrras.2022.100492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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14
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Wang N, Bai X, Wang X, Wang D, Ma G, Zhang F, Ye J, Lu F, Ji C. A Novel Fatty Acid Metabolism-Associated Risk Model for Prognosis Prediction in Acute Myeloid Leukaemia. Curr Oncol 2023; 30:2524-2542. [PMID: 36826154 PMCID: PMC9955245 DOI: 10.3390/curroncol30020193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/09/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults, with an unfavourable outcome and a high rate of recurrence due to its heterogeneity. Dysregulation of fatty acid metabolism plays a crucial role in the development of several tumours. However, the value of fatty acid metabolism (FAM) in the progression of AML remains unclear. In this study, we obtained RNA sequencing and corresponding clinicopathological information from the TCGA and GEO databases. Univariate Cox regression analysis and subsequent LASSO Cox regression analysis were utilized to identify prognostic FAM-related genes and develop a potential prognostic risk model. Kaplan-Meier analysis was used for prognostic significances. We also performed ROC curve to illustrate that the risk model in prognostic prediction has good performance. Moreover, significant differences in immune infiltration landscape were found between high-risk and low-risk groups using ESTIMATE and CIBERSOT algorithms. In the end, differential expressed genes (DEGs) were analyzed by gene set enrichment analysis (GSEA) to preliminarily explore the possible signaling pathways related to the prognosis of FAM and AML. The results of our study may provide potential prognostic biomarkers and therapeutic targets for AML patients, which is conducive to individualized precision therapy.
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Affiliation(s)
- Nana Wang
- Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Xiaoran Bai
- Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Xinlu Wang
- Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Dongmei Wang
- Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Guangxin Ma
- Hematology and Oncology Unit, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Fan Zhang
- Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Jingjing Ye
- Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Fei Lu
- Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
- Correspondence: (F.L.); (C.J.)
| | - Chunyan Ji
- Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China
- Correspondence: (F.L.); (C.J.)
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15
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Gao Z, Bai Y, Lin A, Jiang A, Zhou C, Cheng Q, Liu Z, Chen X, Zhang J, Luo P. Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment. Mol Cancer 2023; 22:31. [PMID: 36793048 PMCID: PMC9930367 DOI: 10.1186/s12943-023-01722-0] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 01/16/2023] [Indexed: 02/17/2023] Open
Abstract
As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy in recent years. They have extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious in tumor patients, have become pioneer drugs in the field of tumor immunotherapy since they were incorporated into clinical practice. In addition, γδT cells that have infiltrated into tumor tissues are found to be in a state of exhaustion or anergy, and there is upregulation of many immune checkpoints (ICs) on their surface, suggesting that γδT cells have a similar ability to respond to ICIs as traditional effector T cells. Studies have shown that targeting ICs can reverse the dysfunctional state of γδT cells in the tumor microenvironment (TME) and exert antitumor effects by improving γδT-cell proliferation and activation and enhancing cytotoxicity. Clarification of the functional state of γδT cells in the TME and the mechanisms underlying their interaction with ICs will solidify ICIs combined with γδT cells as a good treatment option.
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Affiliation(s)
- Zhifei Gao
- grid.284723.80000 0000 8877 7471The Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong 510282 People’s Republic of China ,grid.284723.80000 0000 8877 7471The Second Clinical Medical School, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282 People’s Republic of China
| | - Yifeng Bai
- grid.54549.390000 0004 0369 4060The Department of Oncology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 611731 China
| | - Anqi Lin
- grid.284723.80000 0000 8877 7471The Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong 510282 People’s Republic of China
| | - Aimin Jiang
- grid.73113.370000 0004 0369 1660The Department of Urology, Changhai hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Chaozheng Zhou
- grid.284723.80000 0000 8877 7471The Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong 510282 People’s Republic of China ,grid.284723.80000 0000 8877 7471The First Clinical Medical School, Southern Medical University, Guangzhou, China
| | - Quan Cheng
- grid.216417.70000 0001 0379 7164The Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan China ,grid.216417.70000 0001 0379 7164National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zaoqu Liu
- grid.412633.10000 0004 1799 0733The Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan China
| | - Xin Chen
- The Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
| | - Jian Zhang
- The Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong, 510282, People's Republic of China.
| | - Peng Luo
- The Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong, 510282, People's Republic of China.
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16
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Shen P, Yu J, Long X, Huang X, Tong C, Wang X. Effect of forsythoside A on the transcriptional profile of bovine mammary epithelial cells challenged with lipoteichoic acid. Reprod Domest Anim 2023; 58:89-96. [PMID: 36128756 DOI: 10.1111/rda.14265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/02/2022] [Accepted: 09/19/2022] [Indexed: 01/07/2023]
Abstract
Mastitis is a common disease of the dairy cattle, which affects the development of the dairy industry and leads to huge economic losses. Forsythoside A (FTA) has anti-inflammatory, antioxidant, antiviral and anti-apoptotic effects. However, the therapeutic effect and molecular mechanism of FTA on dairy cow mastitis remain unclear. In this study, bovine mammary epithelial cells (BMECs) were stimulated with lipoteichoic acid (LTA), a key virulence factor of Staphylococcus aureus (S. aureus), to construct in vitro models, and then treated with FTA. Subsequently, the differentially expressed genes (DEGs) in different groups were determined by RNA sequencing (RNA-Seq) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyse the possible function of the DEGs, real-time quantitative PCR (RT-qPCR) was used to verify whether the expression levels of these DEGs were consistent with RNA-Seq results. The results showed that cell division cycle 20B (CDC20B), endothelial cell surface expressed chemotaxis and apoptosis regulator (ECSCR), complement factor H-related 5 (CFHR5) and phospholipase A2 group IVA (PLA2G4A) were down-regulated after FTA treatment. In contrast, Kruppel-like factor 15 (KLF15) and Metallothionein 1E (MT1E) were up-regulated. These DEGs are involved in processes such as apoptosis, inflammation and development of cancer. This study provides valuable insights into the transcriptome changes in BMECs after FTA treatment. Further analysis may help identify the underlying molecular mechanisms.
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Affiliation(s)
- Puxiu Shen
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Jingcheng Yu
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Xiaochuan Long
- College of Animal Science, Phase II, West Campus of Guizhou University, Xibei Community Service Center, Guiyang, Guizhou, China
| | - Xiankai Huang
- College of Animal Science, Phase II, West Campus of Guizhou University, Xibei Community Service Center, Guiyang, Guizhou, China
| | - Chao Tong
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China.,Wushu Overseas Students Pioneer Park, Wuhu, China
| | - Xinzhuang Wang
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
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17
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Giannotta C, Autino F, Massaia M. Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time? Front Immunol 2023; 14:1167443. [PMID: 37143664 PMCID: PMC10153673 DOI: 10.3389/fimmu.2023.1167443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 03/31/2023] [Indexed: 05/06/2023] Open
Abstract
In the last years, the tumor microenvironment (TME) has emerged as a promising target for therapeutic interventions in cancer. Cancer cells are highly dependent on the TME to growth and evade the immune system. Three major cell subpopulations are facing each other in the TME: cancer cells, immune suppressor cells, and immune effector cells. These interactions are influenced by the tumor stroma which is composed of extracellular matrix, bystander cells, cytokines, and soluble factors. The TME can be very different depending on the tissue where cancer arises as in solid tumors vs blood cancers. Several studies have shown correlations between the clinical outcome and specific patterns of TME immune cell infiltration. In the recent years, a growing body of evidence suggests that unconventional T cells like natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells are key players in the protumor or antitumor TME commitment in solid tumors and blood cancers. In this review, we will focus on γδ T cells, especially Vγ9Vδ2 T cells, to discuss their peculiarities, pros, and cons as potential targets of therapeutic interventions in blood cancers.
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Affiliation(s)
- Claudia Giannotta
- Laboratorio di Immunologia dei Tumori del Sangue (LITS), Centro Interdipartimentale di Biotecnologie Molecolari “Guido Tarone”, Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Università Degli Studi di Torino, Torino, Italy
| | - Federica Autino
- Laboratorio di Immunologia dei Tumori del Sangue (LITS), Centro Interdipartimentale di Biotecnologie Molecolari “Guido Tarone”, Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Università Degli Studi di Torino, Torino, Italy
| | - Massimo Massaia
- Laboratorio di Immunologia dei Tumori del Sangue (LITS), Centro Interdipartimentale di Biotecnologie Molecolari “Guido Tarone”, Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Università Degli Studi di Torino, Torino, Italy
- Struttura Complessa (SC) Ematologia, Azienda Ospedaliera (AO) S. Croce e Carle, Cuneo, Italy
- *Correspondence: Massimo Massaia,
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18
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Ping G, Tian Y, Zhou Z. Constructing a Tregs-associated signature to predict the prognosis of colorectal cancer patients: A STROBE-compliant retrospective study. Medicine (Baltimore) 2022; 101:e31382. [PMID: 36451426 PMCID: PMC9704903 DOI: 10.1097/md.0000000000031382] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality worldwide. Regulatory T cells (Tregs) are a key constituent of immune cells in the tumor microenvironment (TME) and are significantly associated with patient outcomes. Our study aimed to construct a Treg-associated signature to predict the prognosis of CRC patients. The genes' expression values and patients' clinicopathological features were downloaded from TCGA and gene expression omnibus (GEO) databases. The single-cell RNA (scRNA) sequencing data of CRC were analyzed through the Deeply Integrated human Single-Cell Omics database. WGCNA analysis was used to select Tregs-associated genes (TrAGs). The infiltrated levels of immune and stromal cells were accessed through the ESTIMATE algorithm. Cox regression analysis and the LASSO algorithm were implemented to construct prognostic models. Gene set enrichment analysis (GSEA) was performed to annotate enriched gene sets. Based on scRNA sequencing data, our study uncovered that more Tregs were significantly enriched in the TME of CRC. Then we identified 123 differentially expressed TrAGs which mainly participated in immune regulation. Given that CRC patients were reclassified into 2 subgroups with distinct overall survival based on 26 differentially expressed TrAGs with prognostic values, we subsequently constructed a signature for CRC. After training and validating in independent cohorts, we proved that this prognostic model can be well applied to predict the prognosis of CRC patients. Further analysis exhibited that more tumor-suppressing immune cells and higher immune checkpoint genes were enriched in CRC patients with high-risk scores. Moreover, immunohistochemistry analysis validated that the genes in the prognostic model were significantly elevated in CRC tissues. We were the first to construct a prognostic signature for CRC based on TrAGs and further revealed that the poor prognosis of patients was mainly attributed to the tumor-suppressing microenvironment and upregulated immune checkpoint genes in tumor tissues.
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Affiliation(s)
- Guoqiang Ping
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yichen Tian
- Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ziqiang Zhou
- Department of Pathology, Zibo Central Hospital, Zibo, Shandong, China
- *Correspondence: Ziqiang Zhou, Department of Pathology, Zibo Central Hospital, No. 54 Gongqingtuanxi Road, Zhangdian District, Zibo 255020, China (e-mail: )
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19
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Pouliquen DL, Malloci M, Boissard A, Henry C, Guette C. Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma. Int J Mol Sci 2022; 23:ijms232213732. [PMID: 36430209 PMCID: PMC9691155 DOI: 10.3390/ijms232213732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 10/31/2022] [Accepted: 11/03/2022] [Indexed: 11/09/2022] Open
Abstract
Curcumin exhibits both immunomodulatory properties and anticarcinogenic effects which have been investigated in different experimental tumor models and cancer types. Its interactions with multiple signaling pathways have been documented through proteomic studies on malignant cells in culture; however, in vivo approaches are scarce. In this study, we used a rat model of highly invasive peritoneal mesothelioma to analyze the residual tumor proteomes of curcumin-treated rats in comparison with untreated tumor-bearing rats (G1) and provide insights into the modifications in the tumor microenvironment/malignant cell crosstalk. The cross-comparing analyses of the histological sections of residual tumors from two groups of rats given curcumin twice on days 21 and 26 after the tumor challenge (G2) or four times on days 7, 9, 11 and 14 (G3), in comparison with G1, identified a common increase in caveolin-1 which linked with significant abundance changes affecting 115 other proteins. The comparison of G3 vs. G2 revealed additional features for 65 main proteins, including an increase in histidine-rich glycoprotein and highly significant abundance changes for 22 other proteins regulating the tumor microenvironment, linked with the presence of numerous activated T cells. These results highlight new features in the multiple actions of curcumin on tumor microenvironment components and cancer cell invasiveness.
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Affiliation(s)
- Daniel L. Pouliquen
- Université d’Angers, Inserm, CNRS, Nantes Université, CRCI2NA, F-49000 Angers, France
- Correspondence: ; Tel.: +33-2-41352854
| | - Marine Malloci
- Nantes Université, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR Bonamy, F-44000 Nantes, France
| | - Alice Boissard
- Université d’Angers, ICO, Inserm, CNRS, Nantes Université, CRCI2NA, F-49000 Angers, France
| | - Cécile Henry
- Université d’Angers, ICO, Inserm, CNRS, Nantes Université, CRCI2NA, F-49000 Angers, France
| | - Catherine Guette
- Université d’Angers, ICO, Inserm, CNRS, Nantes Université, CRCI2NA, F-49000 Angers, France
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20
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Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition. Int J Mol Sci 2022; 23:ijms231810845. [PMID: 36142758 PMCID: PMC9504245 DOI: 10.3390/ijms231810845] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 09/01/2022] [Accepted: 09/13/2022] [Indexed: 11/28/2022] Open
Abstract
The TGF-β signaling pathway is involved in numerous cellular processes, and its deregulation may result in cancer development. One of the key processes in tumor progression and metastasis is epithelial to mesenchymal transition (EMT), in which TGF-β signaling plays important roles. Recently, AGR2 was identified as a crucial component of the cellular machinery responsible for maintaining the epithelial phenotype, thereby interfering with the induction of mesenchymal phenotype cells by TGF-β effects in cancer. Here, we performed transcriptomic profiling of A549 lung cancer cells with CRISPR-Cas9 mediated AGR2 knockout with and without TGF-β treatment. We identified significant changes in transcripts associated with focal adhesion and eicosanoid production, in particular arachidonic acid metabolism. Changes in transcripts associated with the focal adhesion pathway were validated by RT-qPCR of COL4A1, COL4A2, FLNA, VAV3, VEGFA, and VINC mRNAs. In addition, immunofluorescence showed the formation of stress fibers and vinculin foci in cells without AGR2 and in response to TGF-β treatment, with synergistic effects observed. These findings imply that both AGR2 downregulation and TGF-β have a role in focal adhesion formation and cancer cell migration and invasion. Transcripts associated with arachidonic acid metabolism were downregulated after both AGR2 knockout and TGF-β treatment and were validated by RT-qPCR of GPX2, PTGS2, and PLA2G4A. Since PGE2 is a product of arachidonic acid metabolism, its lowered concentration in media from AGR2-knockout cells was confirmed by ELISA. Together, our results demonstrate that AGR2 downregulation and TGF-β have an essential role in focal adhesion formation; moreover, we have identified AGR2 as an important component of the arachidonic acid metabolic pathway.
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Feng C, Wang Z, Liu C, Liu S, Wang Y, Zeng Y, Wang Q, Peng T, Pu X, Liu J. Integrated bioinformatical analysis, machine learning and in vitro experiment-identified m6A subtype, and predictive drug target signatures for diagnosing renal fibrosis. Front Pharmacol 2022; 13:909784. [PMID: 36120336 PMCID: PMC9470879 DOI: 10.3389/fphar.2022.909784] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Renal biopsy is the gold standard for defining renal fibrosis which causes calcium deposits in the kidneys. Persistent calcium deposition leads to kidney inflammation, cell necrosis, and is related to serious kidney diseases. However, it is invasive and involves the risk of complications such as bleeding, especially in patients with end-stage renal diseases. Therefore, it is necessary to identify specific diagnostic biomarkers for renal fibrosis. This study aimed to develop a predictive drug target signature to diagnose renal fibrosis based on m6A subtypes. We then performed an unsupervised consensus clustering analysis to identify three different m6A subtypes of renal fibrosis based on the expressions of 21 m6A regulators. We evaluated the immune infiltration characteristics and expression of canonical immune checkpoints and immune-related genes with distinct m6A modification patterns. Subsequently, we performed the WGCNA analysis using the expression data of 1,611 drug targets to identify 474 genes associated with the m6A modification. 92 overlapping drug targets between WGCNA and DEGs (renal fibrosis vs. normal samples) were defined as key drug targets. A five target gene predictive model was developed through the combination of LASSO regression and stepwise logistic regression (LASSO-SLR) to diagnose renal fibrosis. We further performed drug sensitivity analysis and extracellular matrix analysis on model genes. The ROC curve showed that the risk score (AUC = 0.863) performed well in diagnosing renal fibrosis in the training dataset. In addition, the external validation dataset further confirmed the outstanding predictive performance of the risk score (AUC = 0.755). These results indicate that the risk model has an excellent predictive performance for diagnosing the disease. Furthermore, our results show that this 5-target gene model is significantly associated with many drugs and extracellular matrix activities. Finally, the expression levels of both predictive signature genes EGR1 and PLA2G4A were validated in renal fibrosis and adjacent normal tissues by using qRT-PCR and Western blot method.
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Affiliation(s)
- Chunxiang Feng
- Department of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Guangzhou, Wuhan, China
| | - Zhixian Wang
- Department of Urology, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Urology, Wuhan No. 1 Hospital, Wuhan, China
| | - Chang Liu
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shiliang Liu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuxi Wang
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuanyuan Zeng
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China
| | - Qianqian Wang
- Department of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Guangzhou, Wuhan, China
| | - Tianming Peng
- Department of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Guangzhou, Wuhan, China
| | - Xiaoyong Pu
- Department of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Guangzhou, Wuhan, China
- *Correspondence: Xiaoyong Pu, ; Jiumin Liu,
| | - Jiumin Liu
- Department of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Guangzhou, Wuhan, China
- *Correspondence: Xiaoyong Pu, ; Jiumin Liu,
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22
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Guo Y, Wang M, Zou Y, Jin L, Zhao Z, Liu Q, Wang S, Li J. Mechanisms of chemotherapeutic resistance and the application of targeted nanoparticles for enhanced chemotherapy in colorectal cancer. J Nanobiotechnology 2022; 20:371. [PMID: 35953863 PMCID: PMC9367166 DOI: 10.1186/s12951-022-01586-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 08/04/2022] [Indexed: 11/10/2022] Open
Abstract
Colorectal cancer is considered one of the major malignancies that threaten the lives and health of people around the world. Patients with CRC are prone to post-operative local recurrence or metastasis, and some patients are advanced at the time of diagnosis and have no chance for complete surgical resection. These factors make chemotherapy an indispensable and important tool in treating CRC. However, the complex composition of the tumor microenvironment and the interaction of cellular and interstitial components constitute a tumor tissue with high cell density, dense extracellular matrix, and high osmotic pressure, inevitably preventing chemotherapeutic drugs from entering and acting on tumor cells. As a result, a novel drug carrier system with targeted nanoparticles has been applied to tumor therapy. It can change the physicochemical properties of drugs, facilitate the crossing of drug molecules through physiological and pathological tissue barriers, and increase the local concentration of nanomedicines at lesion sites. In addition to improving drug efficacy, targeted nanoparticles also reduce side effects, enabling safer and more effective disease diagnosis and treatment and improving bioavailability. In this review, we discuss the mechanisms by which infiltrating cells and other stromal components of the tumor microenvironment comprise barriers to chemotherapy in colorectal cancer. The research and application of targeted nanoparticles in CRC treatment are also classified.
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Affiliation(s)
- Yu Guo
- Department of the General Surgery, Jilin University Second Hospital, Changchun, 130000, China
| | - Min Wang
- Department of the General Surgery, Jilin University Second Hospital, Changchun, 130000, China
| | - Yongbo Zou
- Department of the General Surgery, Jilin University Second Hospital, Changchun, 130000, China
| | - Longhai Jin
- Department of Radiology, Jilin University Second Hospital, Changchun, 130000, China
| | - Zeyun Zhao
- Department of the General Surgery, Jilin University Second Hospital, Changchun, 130000, China
| | - Qi Liu
- Department of the General Surgery, Jilin University Second Hospital, Changchun, 130000, China
| | - Shuang Wang
- Department of the Dermatology, Jilin University Second Hospital, Changchun, 130000, China.
| | - Jiannan Li
- Department of the General Surgery, Jilin University Second Hospital, Changchun, 130000, China.
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23
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Yan Y, Huang L, Liu Y, Yi M, Chu Q, Jiao D, Wu K. Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity. J Hematol Oncol 2022; 15:104. [PMID: 35948909 PMCID: PMC9364625 DOI: 10.1186/s13045-022-01322-3] [Citation(s) in RCA: 96] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 07/26/2022] [Indexed: 11/17/2022] Open
Abstract
Characterized by the expression of the critical transcription factor forkhead box protein P3, regulatory T (Treg) cells are an essential part of the immune system, with a dual effect on the pathogenesis of autoimmune diseases and cancer. Targeting Tregs to reestablish the proinflammatory and immunogenic tumor microenvironment (TME) is an increasingly attractive strategy for cancer treatment and has been emphasized in recent years. However, attempts have been significantly hindered by the subsequent autoimmunity after Treg ablation owing to systemic loss of their suppressive capacity. Cellular metabolic reprogramming is acknowledged as a hallmark of cancer, and emerging evidence suggests that elucidating the underlying mechanisms of how intratumoral Tregs acquire metabolic fitness and superior immunosuppression in the TME may contribute to clinical benefits. In this review, we discuss the common and distinct metabolic profiles of Tregs in peripheral tissues and the TME, as well as the differences between Tregs and other conventional T cells in their metabolic preferences. By focusing on the critical roles of different metabolic programs, such as glycolysis, oxidative phosphorylation, fatty acid oxidation, fatty acid synthesis, and amino acid metabolism, as well as their essential regulators in modulating Treg proliferation, migration, and function, we hope to provide new insights into Treg cell-targeted antitumor immunotherapies.
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Affiliation(s)
- Yuheng Yan
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Lan Huang
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Yiming Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Ming Yi
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Qian Chu
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Dechao Jiao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
| | - Kongming Wu
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. .,Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
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24
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Lai WJ, Chen F, Shu L, Yang XM, Yuan J, Xu JB, Leung AYH, He BL. Pivotal role of cytosolic phospholipase PLA2G4A in the pathogenesis of FLT3-ITD-mutated acute myeloid leukemia. Genes Dis 2022; 10:22-25. [PMID: 37013044 PMCID: PMC10066237 DOI: 10.1016/j.gendis.2022.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/22/2022] [Indexed: 11/19/2022] Open
Affiliation(s)
- Wen-Jing Lai
- Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China
| | - Fan Chen
- Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China
| | - Lingling Shu
- Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China
| | - Xin-Ming Yang
- Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China
| | - Jimin Yuan
- Department of Geriatric Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong 518020, China
| | - Jing-Bo Xu
- Department of Hematology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China
| | - Anskar Yu-Hung Leung
- Division of Haematology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong 999077, China
- Corresponding author.
| | - Bai-Liang He
- Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China
- Corresponding author.
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25
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He ZX, Zhao SB, Fang X, E JF, Fu HY, Song YH, Wu JY, Pan P, Gu L, Xia T, Liu YL, Li ZS, Wang SL, Bai Y. Prognostic and Predictive Value of BGN in Colon Cancer Outcomes and Response to Immunotherapy. Front Oncol 2022; 11:761030. [PMID: 35096572 PMCID: PMC8790701 DOI: 10.3389/fonc.2021.761030] [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: 08/19/2021] [Accepted: 12/15/2021] [Indexed: 11/13/2022] Open
Abstract
Background Colon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation. Methods The differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms. Results BGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients. Conclusion BGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.
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Affiliation(s)
- Zi-Xuan He
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Sheng-Bing Zhao
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Xue Fang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Ji-Fu E
- Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Hong-Yu Fu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Yi-Hang Song
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Jia-Yi Wu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Peng Pan
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Lun Gu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Tian Xia
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Yi-Long Liu
- College of Basic Medicine Sciences, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Shu-Ling Wang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
| | - Yu Bai
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
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