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Dittrich K, Yıldız-Altay Ü, Qutab F, Kwong DA, Rao Z, Nievez-Lozano SA, Gardner HL, Richmond JM, London CA. Baseline tumor gene expression signatures correlate with chemoimmunotherapy treatment responsiveness in canine B cell lymphoma. PLoS One 2023; 18:e0290428. [PMID: 37624862 PMCID: PMC10456153 DOI: 10.1371/journal.pone.0290428] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
Pet dogs develop spontaneous diffuse large B cell lymphoma (DLBCL), and veterinary clinical trials have been employed to treat canine DLBCL and to inform clinical trials for their human companions. A challenge that remains is selection of treatment to improve outcomes. The dogs in this study were part of a larger clinical trial evaluating the use of combinations of doxorubicin chemotherapy, anti-CD20 monoclonal antibody, and one of three small molecule inhibitors: KPT-9274, TAK-981, or RV1001. We hypothesized that significant differential expression of genes (DEGs) in the tumors at baseline could help predict which dogs would respond better to each treatment based on the molecular pathways targeted by each drug. To this end, we evaluated gene expression in lymph node aspirates from 18 trial dogs using the NanoString nCounter Canine Immuno-oncology (IO) Panel. We defined good responders as those who relapsed after 90 days, and poor responders as those who relapsed prior to 90 days. We analyzed all dogs at baseline and compared poor responders to good responders, and found increased CCND3 correlated with poor prognosis and increased CD36 correlated with good prognosis, as is observed in humans. There was minimal DEG overlap between treatment arms, prompting separate analyses for each treatment cohort. Increased CREBBP and CDKN1A for KPT-9274, increased TLR3 for TAK-981, and increased PI3Kδ, AKT3, and PTEN, and decreased NRAS for RV1001 were associated with better prognoses. Trends for selected candidate biomarker genes were confirmed via qPCR. Our findings emphasize the heterogeneity in DLBCL, similarities and differences between canine and human DLBCL, and ultimately identify biomarkers that may help guide the choice of chemoimmunotherapy treatment in dogs.
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Affiliation(s)
- Katherine Dittrich
- Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, United States of America
| | | | - Fatima Qutab
- UMass Chan Medical School, Worcester, MA, United States of America
| | - Danny A. Kwong
- UMass Chan Medical School, Worcester, MA, United States of America
| | - Zechuan Rao
- UMass Chan Medical School, Worcester, MA, United States of America
| | | | - Heather L. Gardner
- Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, United States of America
| | | | - Cheryl A. London
- Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, United States of America
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2
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Valdez L, Cheng B, Gonzalez D, Rodriguez R, Campano P, Tsin A, Fang X. Combined treatment with niclosamide and camptothecin enhances anticancer effect in U87 MG human glioblastoma cells. Oncotarget 2022; 13:642-658. [PMID: 35548329 PMCID: PMC9084225 DOI: 10.18632/oncotarget.28227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 04/19/2022] [Indexed: 11/25/2022] Open
Affiliation(s)
- Laura Valdez
- Department of Molecular Science, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
- These authors contributed equally to this work
| | - Benxu Cheng
- Department of Molecular Science, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
- These authors contributed equally to this work
| | - Daniela Gonzalez
- Department of Molecular Science, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
| | - Reanna Rodriguez
- Department of Molecular Science, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
| | - Paola Campano
- Department of Molecular Science, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
| | - Andrew Tsin
- Department of Molecular Science, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
| | - Xiaoqian Fang
- Department of Molecular Science, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
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Gao HX, Wang MB, Li SJ, Niu J, Xue J, Li J, Li XX. Identification of Hub Genes and Key Pathways Associated with Peripheral T-cell Lymphoma. Curr Med Sci 2020; 40:885-899. [PMID: 32980897 DOI: 10.1007/s11596-020-2250-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 06/01/2020] [Indexed: 12/20/2022]
Abstract
Peripheral T-cell lymphoma (PTCL) is a very aggressive and heterogeneous hematological malignancy and has no effective targeted therapy. The molecular pathogenesis of PTCL remains unknown. In this study, we chose the gene expression profile of GSE6338 from the Gene Expression Omnibus (GEO) database to identify hub genes and key pathways and explore possible molecular pathogenesis of PTCL by bioinformatic analysis. Differentially expressed genes (DEGs) between PTCL and normal T cells were selected using GEO2R tool. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, the Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) were utilized to construct protein-protein interaction (PPI) network and perform module analysis of these DEGs. A total of 518 DEGs were identified, including 413 down-regulated and 105 up-regulated genes. The down-regulated genes were enriched in osteoclast differentiation, Chagas disease and mitogen-activated protein kinase (MAPK) signaling pathway. The up-regulated genes were mainly associated with extracellular matrix (ECM)-receptor interaction, focal adhesion and pertussis. Four important modules were detected from the PPI network by using MCODE software. Fifteen hub genes with a high degree of connectivity were selected. Our study identified DEGs, hub genes and pathways associated with PTCL by bioinformatic analysis. Results provide a basis for further study on the pathogenesis of PTCL.
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Affiliation(s)
- Hai-Xia Gao
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.,Xinjiang Medical University, Urumqi, 830011, China.,Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, 832002, China
| | - Meng-Bo Wang
- Department of Ultrasound, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, 832002, China
| | - Si-Jing Li
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.,Xinjiang Medical University, Urumqi, 830011, China
| | - Jing Niu
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.,Xinjiang Medical University, Urumqi, 830011, China
| | - Jing Xue
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.,Xinjiang Medical University, Urumqi, 830011, China
| | - Jun Li
- Department of Ultrasound, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, 832002, China
| | - Xin-Xia Li
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
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Wang B, Wang Z, Han L, Gong S, Wang Y, He Z, Feng Y, Yang Z. Prognostic significance of cyclin D3 expression in malignancy patients: a meta-analysis. Cancer Cell Int 2019; 19:158. [PMID: 31198407 PMCID: PMC6558842 DOI: 10.1186/s12935-019-0865-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 05/27/2019] [Indexed: 01/05/2023] Open
Abstract
Background As a pivotal regulator, cyclin D3 gives play to a crucial value in conversion from the G1 stage to the S stage of cell cycle, which is implicated in tumor progression, especially proliferation
and migration. Recent literatures have reported that cyclin D3 could predict survival time of malignancy patients. But, its prognostic role of cyclin D3 in neoplasms remains controversial. Methods Databases involving EMBASE, PubMed and Web of Science were carefully searched, and literatures investigating the prognostic effect of aberrantly expressing cyclin D3 among human cancers were collected for further analysis. We used both hazards ratios and its corresponding 95% confidence intervals to evaluate the connection among the survival rate of malignancy patients and the expression of cyclin D3. Results There were 13 eligible researches involving 16 cohorts and 2395 participants which were included in this study. The outcomes suggested that highly expressing cyclin D3 was significantly correlated with worse clinical prognosis of overall survival (HR 1.88; 95% CI 1.31–2.69) and disease specific survival (HR 2.68; 95% CI 1.35–5.31). But there existed no significant connection between the elevated expression of cyclin D3 with disease free survival (HR 2.65; 95% CI 0.83–8.46), recurrence-free survival (HR 2.86; 95% CI 0.82–9.96) and progression-free survival (HR 5.24; 95% CI 0.46–60.25) of diffident kinds of malignancy patients. Moreover, we discovered that elevated cyclin D3 expression was significantly connected with decreased overall survival in lymphoma (HR 3.72; 95% CI 2.18–6.36) while no significant relevance between highly expressing cyclin D3 and the overall survival in breast cancer was obtained (HR 2.12; 95% CI 0.76–5.91). Conclusions This meta-analysis demonstrated that highly expressing cyclin D3 might be an unfavorable prognostic biomarker for various malignancy patients, which can make great contributions to the clinical diagnosis and treatment.
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Affiliation(s)
- Bo Wang
- 1Department of Rehabilitation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Zijian Wang
- 2Department of Orthopedics, Xiangyang Central Hospital Affiliated Hubei University of Arts and Science, Xiangyang, 441021 China
| | - Lizhi Han
- 3Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Song Gong
- 3Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Yanxue Wang
- 1Department of Rehabilitation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Zhiwen He
- 1Department of Rehabilitation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Yong Feng
- 3Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Zhaohui Yang
- 1Department of Rehabilitation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
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Chen Y, Mei X, Gan D, Wu Z, Cao Y, Lin M, Zhang N, Yang T, Chen Y, Hu J. Integration of bioinformatics and experiments to identify TP53 as a potential target in Emodin inhibiting diffuse large B cell lymphoma. Biomed Pharmacother 2018; 107:226-233. [PMID: 30096626 DOI: 10.1016/j.biopha.2018.07.168] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 07/26/2018] [Accepted: 07/31/2018] [Indexed: 12/15/2022] Open
Abstract
Non-Hodgkin's Lymphoma (NHL) is a group of lymphoid malignancies with unsatisfactory treatment effect in some aggressive subtypes, including diffuse large B cell lymphoma (DLBCL). Emodin is an anthraquinone with potent anti-cancer activities. However, the molecular mechanism of Emodin repressing aggressive NHL remains to be revealed in detail. This study delineated the active mechanism of Emodin action in aggressive NHL by using bioinformatics analysis and in vitro assay. 4 Emodin's primary direct protein targets (DPT) were identified and the DPTs-associated proteins/genes were predicted. Those Emodin-related proteins/genes were subject to enrich Emodin-associated pathways, from which 3 significantly NHL-related signal pathways were refined identified. Advanced integrated analysis exhibited TP53 and PI3K as the significant molecule and pathway by which Emodin may function in NHL. To verify those bioinformatics findings, effects of Emodin and E35, a novel derivative of emodin were investigated on DLBCL cell lines SU-DHL4. Emodin and E35 suppressed proliferation and induced apoptosis of SU-DHL4 cells in a time- and dose-dependent manner. Emodin and E35 declined TP53 protein expression and decreased phosphorylation of PI3K/AKT protein in a dose-dependent manner. All of above showed that combined bioinformatics analysis with experiments offered a novel approach for outlining the mechanisms of Emodin action in DLBCL with convenience and integrity.
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Affiliation(s)
- Yanxin Chen
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China
| | - Xuqiao Mei
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China
| | - Donghui Gan
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China
| | - Zhengjun Wu
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China
| | - Yanqin Cao
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China
| | - Minhui Lin
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China
| | - Na Zhang
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China
| | - Ting Yang
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China
| | - Yingyu Chen
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China.
| | - Jianda Hu
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China.
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Wu X, Wang F, Li Y, Wang X, Liu P, Zhang H, Ge Z, Zhang X, Gao C, Chen B. Evaluation of latent membrane protein 1 and microRNA-155 for the prognostic prediction of diffuse large B cell lymphoma. Oncol Lett 2018; 15:9725-9734. [PMID: 29844839 PMCID: PMC5958882 DOI: 10.3892/ol.2018.8560] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 03/16/2018] [Indexed: 12/23/2022] Open
Abstract
Diffuse large B cell lymphoma (DLBCL) has previously been demonstrated to contribute to the mortality of lymphoma with various aggressive features. The prognostic role of the biomarkers latent membrane protein (LMP) 1 and microRNA-(miR)-155 in DLBCL remain controversial. The present study primarily aimed to assess the effect of LMP1 and miR-155 on the survival of DLBCL patients, and additionally evaluate the clinical features to observe their influence on outcomes, compared with previous studies. Formalin-fixed and paraffin-embedded samples were collected from our center between May 2010 and December 2011. Microarray analysis, immunohistochemical analysis and reverse transcription-quantitative polymerase chain reaction were used to evaluate the expression of LMP1 and miR-155. The association between biomarkers or clinical features and patient outcomes was assessed using the log-rank statistical test, Cox proportional hazard model and Kaplan-Meier method. SPSS software was used to statistically analyze the data. A total of 82 patients were included in the present study. The results demonstrated that high expression of LMP1 and miR-155 may be associated with a poor progression-free survival rate, while a high International Prognostic Index score and high expression of LMP1 may be associated with a poor overall survival rate. These results indicated that LMP1 and miR-155 may be novel and reliable biomarkers for the prognostic prediction of lymphoma, and will potentially be analyzed in the future to evaluate patient prognosis.
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Affiliation(s)
- Xue Wu
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Fei Wang
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Yuan Li
- Department of Oncology, Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Xiyong Wang
- Department of Oncology, Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Ping Liu
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Haijun Zhang
- Department of Oncology, Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Zheng Ge
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Xiaoping Zhang
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Chong Gao
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Baoan Chen
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
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Sato M, Mochizuki H, Goto-Koshino Y, Fujiwara-Igarashi A, Takahashi M, Ohno K, Tsujimoto H. Prognostic significance of hypermethylation of death-associated protein kinase (DAPK) gene CpG island in dogs with high-grade B-cell lymphoma. Vet Comp Oncol 2018. [DOI: 10.1111/vco.12395] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- M. Sato
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science; The University of Tokyo; Tokyo Japan
| | - H. Mochizuki
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science; The University of Tokyo; Tokyo Japan
| | - Y. Goto-Koshino
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science; The University of Tokyo; Tokyo Japan
| | - A. Fujiwara-Igarashi
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science; The University of Tokyo; Tokyo Japan
| | - M. Takahashi
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science; The University of Tokyo; Tokyo Japan
| | - K. Ohno
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science; The University of Tokyo; Tokyo Japan
| | - H. Tsujimoto
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science; The University of Tokyo; Tokyo Japan
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