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Original Articles
- Prognostic Significance of EPHB2 Expression in Colorectal Cancer Progression
- Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Gyeong Hoon Kang
- J Pathol Transl Med. 2018;52(5):298-306. Published online July 18, 2018
- DOI: https://doi.org/10.4132/jptm.2018.06.29
- 6,133 View
- 145 Download
- 15 Web of Science
- 11 Crossref
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Abstract
PDF - Background
A receptor tyrosine kinase for ephrin ligands, EPHB2, is expressed in normal colorectal tissues and colorectal cancers (CRCs). The aim of this study was to investigate EPHB2 expression over CRC progression and determine its prognostic significance in CRC.
Methods
To measure EPHB2 mRNA and protein expression, real-time polymerase chain reaction and immunohistochemistry were performed in 32 fresh-frozen and 567 formalin-fixed paraffin-embedded CRC samples, respectively. We further investigated clinicopathological features and overall and recurrence-free survival according to EPHB2 protein expression.
Results
The EPHB2 level was upregulated in CRC samples compared to non-cancerous tissue in most samples and showed a strong positive correlation with AXIN2. Notably, CD44 had a positive association with both mRNA and protein levels of EPHB2. Immunohistochemical analysis revealed no difference in EPHB2 expression between adenoma and carcinoma areas. Although EPHB2 expression was slightly lower in invasive fronts compared to surface area (p < .05), there was no difference between superficial and metastatic areas. EPHB2 positivity was associated with lymphatic (p < .001) and venous (p = .001) invasion, TNM stage (p < .001), and microsatellite instability (p = .036). Kaplan–Meier analysis demonstrated that CRC patients with EPHB2 positivity showed better clinical outcomes in both overall (p = .049) and recurrence-free survival (p = .015). However, multivariate analysis failed to show that EPHB2 is an independent prognostic marker in CRCs (hazard ratio, 0.692; p = .692).
Conclusions
Our results suggest that EPHB2 is overexpressed in a subset of CRCs and is a significant prognostic marker. -
Citations
Citations to this article as recorded by
- Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets
João Figueira Scarini, Moisés Willian Aparecido Gonçalves, Reydson Alcides de Lima-Souza, Luccas Lavareze, Talita Kimura, Ching-Chu Yang, Albina Altemani, Fernanda Viviane Mariano, Heloisa Prado Soares, Gary Chris Fillmore, Erika Said Abu Egal
Frontiers in Oncology.2024;[Epub] CrossRef - Therapeutic effects of ephrin B receptor 2 inhibitors screened by molecular docking on cutaneous squamous cell carcinoma
Yan Li, Xuanfen Zhang
Journal of Dermatological Treatment.2022; 33(1): 373. CrossRef - The EPH/Ephrin System in Colorectal Cancer
Stavros P. Papadakos, Leonidas Petrogiannopoulos, Alexandros Pergaris, Stamatios Theocharis
International Journal of Molecular Sciences.2022; 23(5): 2761. CrossRef - Prognostic Significance of Autophagy-Relevant Gene Markers in Colorectal Cancer
Qinglian He, Ziqi Li, Jinbao Yin, Yuling Li, Yuting Yin, Xue Lei, Wei Zhu
Frontiers in Oncology.2021;[Epub] CrossRef - Genetic Predisposition to Numerous Large Ulcerating Basal Cell Carcinomas and Response to Immune Therapy
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International Journal of Dermatology and Venereology.2021; 4(2): 70. CrossRef - Delineation of colorectal cancer ligand-receptor interactions and their roles in the tumor microenvironment and prognosis
Hexin Lin, Lu Xia, Jiabian Lian, Yinan Chen, Yiyi Zhang, Zhicheng Zhuang, HuaJun Cai, Jun You, Guoxian Guan
Journal of Translational Medicine.2021;[Epub] CrossRef - Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses
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Respiratory Research.2020;[Epub] CrossRef - The role of Eph receptors in cancer and how to target them: novel approaches in cancer treatment
Oscar J Buckens, Btissame El Hassouni, Elisa Giovannetti, Godefridus J Peters
Expert Opinion on Investigational Drugs.2020; 29(6): 567. CrossRef - Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer
Bo Jang, Hye Kim, Jeong Bae, Woo Kim, Chang Hyun, Gyeong Kang
Biomolecules.2020; 10(4): 602. CrossRef Gene Expression Signature to Predict Prognosis and Adjuvant Chemosensitivity of Colorectal Cancer Patients
Jianxia Li, Jianwei Zhang, Huabin Hu, Yue Cai, Jiayu Ling, Zehua Wu, Yanhong Deng
Cancer Management and Research.2020; Volume 12: 3301. CrossRef- SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers
Bo Gun Jang, Hye Sung Kim, Jeong Mo Bae, Woo Ho Kim, Heung Up Kim, Gyeong Hoon Kang
Scientific Reports.2020;[Epub] CrossRef
- Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets
- Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma
- Hyun Min Koh, Bo Geun Jang, Chang Lim Hyun, Young Sill Kim, Jin Won Hyun, Weon Young Chang, Young Hee Maeng
- J Pathol Transl Med. 2017;51(1):32-39. Published online December 25, 2016
- DOI: https://doi.org/10.4132/jptm.2016.10.17
- 8,290 View
- 178 Download
- 23 Web of Science
- 24 Crossref
-
Abstract
PDF
- Background
Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea.
Methods
AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues.
Results
AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001).
Conclusions
AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients. -
Citations
Citations to this article as recorded by- Neutralizing IL-16 enhances the efficacy of targeting Aurora-A therapy in colorectal cancer with high lymphocyte infiltration through restoring anti-tumor immunity
Shiang-Jie Yang, Sheng-Tsung Chang, Kung-Chao Chang, Bo-Wen Lin, Kwang-Yu Chang, Yao-Wen Liu, Ming-Derg Lai, Liang-Yi Hung
Cell Death & Disease.2024;[Epub] CrossRef - Development and validation of epigenetic modification-related signals for the diagnosis and prognosis of colorectal cancer
Xia Li, Jingjing Li, Jie Li, Nannan Liu, Liwei Zhuang
BMC Genomics.2024;[Epub] CrossRef - Exploring Core Genes by Comparative Transcriptomics Analysis for Early Diagnosis, Prognosis, and Therapies of Colorectal Cancer
Md. Ariful Islam, Md. Bayazid Hossen, Md. Abu Horaira, Md. Alim Hossen, Md. Kaderi Kibria, Md. Selim Reza, Khanis Farhana Tuly, Md. Omar Faruqe, Firoz Kabir, Rashidul Alam Mahumud, Md. Nurul Haque Mollah
Cancers.2023; 15(5): 1369. CrossRef - The Oncology Biomarker Discovery framework reveals cetuximab and bevacizumab response patterns in metastatic colorectal cancer
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Nature Communications.2023;[Epub] CrossRef - Potential Signature Therapeutic Biomarkers TOP2A, MAD2L1, and CDK1 in Colorectal Cancer: A Systems Biomedicine-Based Approach
P. Priyamvada, Sudha Ramaiah
Biochemical Genetics.2023;[Epub] CrossRef - Disease Modeling on Tumor Organoids Implicates AURKA as a Therapeutic Target in Liver Metastatic Colorectal Cancer
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Murdani Abdullah, DR Noor, Amanda Pitarini Utari, Virly Nanda Muzellina, Nur Rahadiani, Radiana Dhewayani Antarianto
F1000Research.2022; 11: 182. CrossRef - Mitotic protein kinase-driven crosstalk of machineries for mitosis and metastasis
Chang-Hyeon Kim, Da-Eun Kim, Dae-Hoon Kim, Ga-Hong Min, Jung-Won Park, Yeo-Bin Kim, Chang K. Sung, Hyungshin Yim
Experimental & Molecular Medicine.2022; 54(4): 414. CrossRef - AURKA is a prognostic biomarker for good overall survival in stage II colorectal cancer patients
Peter Jung, David Horst, Thomas Kirchner, Frederick Klauschen, Jens Neumann
Pathology - Research and Practice.2022; 235: 153936. CrossRef - Therapeutic Potential of Mitotic Kinases’ Inhibitors in Cancers of the Gastrointestinal System
Aadil Javed, Gianluca Malagraba, Mahdieh Yarmohammadi, Catalina M. Perelló-Reus, Carles Barceló, Teresa Rubio-Tomás
Future Pharmacology.2022; 2(3): 214. CrossRef - Bioinformatics Analysis of RNA-seq Data Reveals Genes Related to Cancer Stem Cells in Colorectal Cancerogenesis
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International Journal of Molecular Sciences.2022; 23(21): 13252. CrossRef - Unweaving the mitotic spindle: A focus on Aurora kinase inhibitors in lung cancer
Alessio Stefani, Geny Piro, Francesco Schietroma, Alessandro Strusi, Emanuele Vita, Simone Fiorani, Diletta Barone, Federico Monaca, Ileana Sparagna, Giustina Valente, Miriam Grazia Ferrara, Ettore D’Argento, Mariantonietta Di Salvatore, Carmine Carbone,
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Life Sciences.2020; 262: 118491. CrossRef - Inhibition of AURKA Reduces Proliferation and Survival of Gastrointestinal Cancer Cells With Activated KRAS by Preventing Activation of RPS6KB1
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- Neutralizing IL-16 enhances the efficacy of targeting Aurora-A therapy in colorectal cancer with high lymphocyte infiltration through restoring anti-tumor immunity
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