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Prediction of Lymph Node Metastasis by Tumor Dimension Versus Tumor Biological Properties in Head and Neck Squamous Cell Carcinomas
Jeon Yeob Jang, Min Ji Kim, Gwanghui Ryu, Nayeon Choi, Young-Hyeh Ko, Han-Sin Jeong
Cancer Res Treat. 2016;48(1):54-62.   Published online March 6, 2015
DOI: https://doi.org/10.4143/crt.2014.332
AbstractAbstract PDFPubReaderePub
Purpose
Lymph node metastasis (LNM) is a strong prognostic factor in many solid cancers, including head and neck squamous cell carcinomas (HNSCC), and LNM can be dependent upon primary tumor biology, as well as tumor dimension. Here, we investigate the relative risk of LNM in accordance to tumor dimension and biology in HNSCC subsites.
Materials and Methods
Medical data of 295 HNSCC patients who had undergone the initial curative surgery (oral tongue 174, oropharynx 75, hypopharynx 46) were analyzed to identify the significant predictive factor for LNM. Tumor volume and thickness were set as tumor dimensional variables, and biological variables included lymphovascular, perineural invasion, and tumor differentiation. Statistical analyses were conducted to assess the predictability of LNM from variables, and subgroup analyses according to the tumor subsites. In addition, we evaluated the impacts of tumor dimension and biological variables on the treatment outcomes and survival in HNSCC subsites.
Results
The overall tumor dimension and biological variables had a similar impact on the prediction of LNM in HNSCC (area under curve, 0.7682 and 0.7717). The prediction sensitivity of LNM in oral tongue cancer was mainly dependent on tumor dimension, while LNM in oro- and hypo-pharynx cancers was more influenced by biological factors. Survival analyses also confirmed that biological factor was more powerful in estimating disease-free survival of hypopharyngeal cancer patients, while tumor dimension was more significant in that of oral cancer patients.
Conclusion
Tumor dimension and biology have a significant, tumor subsite-dependent impact on the occurrence of LNM and disease-free survival in HNSCC.

Citations

Citations to this article as recorded by  
  • Extra-Capsular Spread of Lymph Node Metastasis in Oral, Oropharyngeal and Hypopharyngeal Cancer: A Comparative Subsite Analysis
    Yung Jee Kang, Goeun Park, Sung Yool Park, Taehwan Kim, Eunhye Kim, Yujin Heo, Changhee Lee, Han-Sin Jeong
    Cancers.2024; 16(3): 659.     CrossRef
  • The Prognostic Role of Perineural Invasion for Survival in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
    Zhuo-Ying Tao, Guang Chu, Yu-Xiong Su
    Cancers.2024; 16(14): 2514.     CrossRef
  • A preoperative nomogram model for the prediction of lymph node metastasis in buccal mucosa cancer
    Qian Chen, Rui Wei, Shan Li
    Cancer Medicine.2023; 12(13): 14120.     CrossRef
  • The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma
    Wendu Pang, Yaxin Luo, Junhong Li, Danni Cheng, Yufang Rao, Minzi Mao, Ke Qiu, Yijun Dong, Jun Liu, Jian Zou, Haiyang Wang, Fei Chen
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • Crosstalk between head and neck cancer cells and lymphatic endothelial cells promotes tumor metastasis via CXCL5‐CXCR2 signaling
    Bok‐Soon Lee, Jeon Yeob Jang, Chorong Seo, Chul‐Ho Kim
    The FASEB Journal.2021;[Epub]     CrossRef
  • A nomogram for predicting occult lymph node metastasis in early hypopharyngeal cancer with cN0
    Xiaohui Yuan, Chi-Yao Hsueh, Ming Zhang, Lei Tao, Liang Zhou
    European Archives of Oto-Rhino-Laryngology.2021; 278(9): 3515.     CrossRef
  • Individualized elective irradiation of the clinically node‐negative neck in definitive radiotherapy for head and neck squamous cell carcinoma
    Jia Kou, Li Lin, Cheng‐Yang Jiao, Meng‐Qiu Tian, Guan‐Qun Zhou, Xue Jiang, Jun Ma, Zhen‐Yu Qi, Yao Lu, Ying Sun
    Cancer Communications.2021; 41(4): 303.     CrossRef
  • The prognostic value of tumor depth for cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas
    Lu‐Lu Ye, Jia Rao, Xing‐Wen Fan, Fang‐Fang Kong, Chao‐Su Hu, Hong‐Mei Ying
    Head & Neck.2019; 41(7): 2116.     CrossRef
  • Patients with unilateral squamous cell carcinoma of the tongue and ipsilateral lymph node metastasis do not profit from bilateral neck dissection
    Christoph Klingelhöffer, Andreas Gründlinger, Gerrit Spanier, Stephan Schreml, Maximilian Gottsauner, Steffen Mueller, Johannes K. Meier, Torsten E. Reichert, Tobias Ettl
    Oral and Maxillofacial Surgery.2018; 22(2): 185.     CrossRef
  • Comparison of tumor volume, thickness, and T classification as predictors of outcomes in surgically treated squamous cell carcinoma of the oral tongue
    Manish Mair, Deepa Nair, Sudhir Nair, Akshat Malik, Aseem Mishra, Sadhana Kannan, Saurabh Bobdey, Hitesh Singhvi, Pankaj Chaturvedi
    Head & Neck.2018; 40(8): 1667.     CrossRef
  • pN status predicts outcomes in surgically treated pT1–pT2 patients of various disease stages with squamous cell carcinoma of the head and neck: a 17-year retrospective single center cohort study
    Xu Qian, Branko Sinikovic, Frank Schreiber, Sebastian Ochsenreither, Konrad Klinghammer, Barbara Wollenberg, Andreas M. Kaufmann, Andreas E. Albers
    European Archives of Oto-Rhino-Laryngology.2018; 275(11): 2787.     CrossRef
  • Predictive markers for delayed lymph node metastases and survival in early-stage oral squamous cell carcinoma
    Ivica Luksic, Petar Suton
    Head & Neck.2017; 39(4): 694.     CrossRef
  • Measurement of tumor volume is not superior to diameter for prediction of lymph node metastasis in early gastric cancer with minute submucosal invasion
    Jeung Hui Pyo, Sun-Ju Byeon, Hyuk Lee, Yang Won Min, Byung-Hoon Min, Jun Haeng Lee, Kyoung-Mee Kim, Hyeon Seon Ahn, Kyunga Kim, Yoon-Ho Choi, Jae J. Kim
    Oncotarget.2017; 8(69): 113758.     CrossRef
  • Mechanisms of Lymph Node Metastasis in Head and Neck Cancer
    Jeon Yeob Jang
    Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2016; 59(4): 259.     CrossRef
  • Analysis of angiogenic markers in oral squamous cell carcinoma-gene and protein expression
    Susanne Jung, Sonja Sielker, Nikolai Purcz, Christoph Sproll, Yahya Acil, Johannes Kleinheinz
    Head & Face Medicine.2015;[Epub]     CrossRef
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APE1/Ref-1 as a Serological Biomarker for the Detection of Bladder Cancer
Ju Hyun Shin, Sunga Choi, Yu Ran Lee, Myoung Soo Park, Yong Gil Na, Kaikobad Irani, Sang Do Lee, Jin Bong Park, Jin Man Kim, Jae Sung Lim, Byeong Hwa Jeon
Cancer Res Treat. 2015;47(4):823-833.   Published online January 2, 2015
DOI: https://doi.org/10.4143/crt.2014.074
AbstractAbstract PDFPubReaderePub
Purpose
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that shows elevated expression in a number of cancers. We attempted to determine whether serum APE1/Ref-1 is elevated in patients with bladder cancer.
Materials and Methods
Serum APE1/Ref-1 levels were determined using enzyme-linked immunosorbent assay in serum from patients with bladder cancer who had not received chemotherapy or radiotherapy (n=51) and non-tumor controls (n=55). The area under the receiver operating characteristic area under the curve was applied to determine the correlation between clinical factors and the serum levels of APE1/Ref-1.
Results
Serum levels of APE1/Ref-1 in bladder cancer patients were significantly elevated compared to those of the control group (3.548±0.333 ng/100 μL [n=51] for bladder cancer vs. 1.547±0.319 ng/100 μL [n=55] for the control group), with a sensitivity and specificity of 93% and 59%, respectively. Serum APE1/Ref-1 levels are associated with tumor stage, grade, muscle invasion, and recurrence.
Conclusion
Serum APE1/Ref-1 might be useful as a potential serologic biomarker for bladder cancer.

Citations

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    Chemical Communications.2024; 60(35): 4695.     CrossRef
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    Analytical Methods.2024; 16(36): 6220.     CrossRef
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    Lei Yang, Zhipeng Sun
    Molecular and Clinical Oncology.2024;[Epub]     CrossRef
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    Materials & Design.2023; 226: 111611.     CrossRef
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    Sensors and Actuators B: Chemical.2023; 381: 133425.     CrossRef
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    Chinese Journal of Chemistry.2023; 41(12): 1437.     CrossRef
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    Cells.2023; 12(14): 1895.     CrossRef
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    Biomedicines.2022; 10(1): 190.     CrossRef
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    Nucleic Acids Research.2022; 50(4): 2211.     CrossRef
  • APE1/Ref-1 Role in Inflammation and Immune Response
    Thais Teixeira Oliveira, Leonam Gomes Coutinho, Laysa Ohana Alves de Oliveira, Ana Rafaela de Souza Timoteo, Guilherme Cavalcanti Farias, Lucymara Fassarella Agnez-Lima
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    Gamze TUNA
    Journal of Basic and Clinical Health Sciences.2022; 6(3): 851.     CrossRef
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    Leorik Pereira Silva, Thalita Santana, Bruno Tavares Sedassari, Suzana Machado de Sousa, Ana Paula Veras Sobral, Roseana de Almeida Freitas, Carlos Augusto Galvão Barboza, Lélia Batista de Souza
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  • Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
    Fenil Shah, Derek Logsdon, Richard A. Messmann, Jill C. Fehrenbacher, Melissa L. Fishel, Mark R. Kelley
    npj Precision Oncology.2017;[Epub]     CrossRef
  • APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing
    Fenil Shah, Emery Goossens, Nadia M. Atallah, Michelle Grimard, Mark R. Kelley, Melissa L. Fishel
    Molecular Oncology.2017; 11(12): 1711.     CrossRef
  • Elevation of Serum APE1/Ref-1 in Experimental Murine Myocarditis
    Seon-Ah Jin, Byung-Kwan Lim, Hee Seo, Sun Kim, Kye Ahn, Byeong Jeon, Jin-Ok Jeong
    International Journal of Molecular Sciences.2017; 18(12): 2664.     CrossRef
  • APE1 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis
    Chun-Ling Yuan, Fan He, Jia-Zhou Ye, Hui-Ni Wu, Jin-Yan Zhang, Zhi-Hui Liu, Yong-Qiang Li, Xiao-Ling Luo, Yan Lin, Rong Liang
    Oncotarget.2017; 8(35): 59720.     CrossRef
  • Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker
    Sunga Choi, Ju Hyun Shin, Yu Ran Lee, Hee Kyoung Joo, Ki Hak Song, Yong Gil Na, Seok Jong Chang, Jae Sung Lim, Byeong Hwa Jeon
    Disease Markers.2016; 2016: 1.     CrossRef
  • Secreted APE1/Ref-1 inhibits TNF-α-stimulated endothelial inflammation via thiol-disulfide exchange in TNF receptor
    Myoung Soo Park, Sunga Choi, Yu Ran Lee, Hee Kyoung Joo, Gun Kang, Cuk-Seong Kim, Soo Jin Kim, Sang Do Lee, Byeong Hwa Jeon
    Scientific Reports.2016;[Epub]     CrossRef
  • Altered Secretory Activity of APE1/Ref-1 D148E Variants Identified in Human Patients With Bladder Cancer
    Yu Ran Lee, Jae Sung Lim, Ju Hyun Shin, Sunga Choi, Hee Kyoung Joo, Byeong Hwa Jeon
    International Neurourology Journal.2016; 20(Suppl 1): S30.     CrossRef
  • Dynamic Regulation of APE1/Ref-1 as a Therapeutic Target Protein
    Sunga Choi, Hee Kyoung Joo, Byeong Hwa Jeon
    Chonnam Medical Journal.2016; 52(2): 75.     CrossRef
  • Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients
    Shiheng Zhang, Le He, Nan Dai, Wei Guan, Jinlu Shan, Xueqin Yang, Zhaoyang Zhong, Yi Qing, Feng Jin, Chuan Chen, Yuxin Yang, Hongyi Wang, Laura Baugh, Gianluca Tell, David M. Wilson, Mengxia Li, Dong Wang
    Oncotarget.2016; 7(47): 77482.     CrossRef
  • 15,413 View
  • 139 Download
  • 59 Web of Science
  • 58 Crossref
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CCL2 Chemokine as a Potential Biomarker for Prostate Cancer: A Pilot Study
Igor Tsaur, Anika Noack, Jasmina Makarevic, Elsie Oppermann, Ana Maria Waaga-Gasser, Martin Gasser, Hendrik Borgmann, Tanja Huesch, Kilian M. Gust, Michael Reiter, David Schilling, Georg Bartsch, Axel Haferkamp, Roman A. Blaheta
Cancer Res Treat. 2015;47(2):306-312.   Published online October 13, 2014
DOI: https://doi.org/10.4143/crt.2014.015
AbstractAbstract PDFPubReaderePub
Purpose
Prostate specific antigen is not reliable in diagnosing prostate cancer (PCa), making the identification of novel, precise diagnostic biomarkers important. Since chemokines are associated with more aggressive disease and poor prognosis in diverse malignancies, we aimed to investigate the diagnostic relevance of chemokines in PCa. Materials and Methods Preoperative and early postoperative serum samples were obtained from 39 consecutive PCa patients undergoing radical prostatectomy. Serum from 15 healthy volunteers served as controls. Concentrations of CXCL12, CXCL13, CX3CL1, CCL2, CCL5, and CCL20 were measured in serum by Luminex. The expression activity of CXCR3, CXCR4, CXCR5, CXCR7, CXCL12, CXCL13, CX3CR1, CXCL1, CCR2, CCR5, CCR6, CCR7, CCL2, and CCL5 mRNA was assessed in tumor and adjacent normal tissue of prostatectomy specimens by quantitative real-time polymerase chain reaction. The associations of these chemokines with clinical and histological parameters were tested. Results The gene expression activity of CCL2 and CCR6 was significantly higher in tumor tissue compared to adjacent normal tissue. CCL2 was also significantly higher in the blood samples of PCa patients, compared to controls. CCL5, CCL20, and CX3CL1 were lower in patient serum, compared to controls. CCR2 tissue mRNA was negatively correlated with the Gleason score and grading. Conclusion Chemokines are significantly modified during tumorigenesis of PCa, and CCL2 is a promising diagnostic biomarker.

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