Yi-Chen Lee1, Tzu Chieh Yin2, Yi-Ting Chen3, Chee-Yin Chai4, Jaw Yuan Wang2, Mei-Chi Liu5, Yuan-Chien Lin6, Jung Yu Kan7. 1. Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. Department of Surgery, Division of Gastrointestinal and General Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C. 3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 4. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 5. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 6. Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 7. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. Department of Surgery, Division of Gastrointestinal and General Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C. jykankmu@gmail.com.
Abstract
BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. DNA double-strand breaks (DSBs) are deleterious lesions that can lead to chromosomal anomalies, genomic instability and cancer. The histone H2AX plays an important role in response to DNA damage and phosphorylation of H2AX (p-H2AX) is evidence of DSBs. The aim of this study was to evaluate the clinical significance of p-H2AX expression in CRC. PATIENTS AND METHODS: p-H2AX expression in CRC tissues was analyzed by immunohistochemistry and correlated with clinicopathological variables using the chi-square test. The prognostic value of p-H2AX for distant metastasis-free survival (DMFS) and overall survival (OS) was evaluated by Kaplan-Meier estimates and the individual prognostic components were analyzed with Cox regression analysis. RESULTS: A high p-H2AX expression in CRC tissues was associated with tumor stage and perineurial invasion. Furthermore, a high p-H2AX expression was associated with poor DMFS and OS. Cox regression analysis also revealed that p-H2AX was an independent predictor of DMFS and OS. CONCLUSION: A high p-H2AX expression in CRC tissues is associated with a more malignant cancer behavior, as well as poor patient survival. p-H2AX may, therefore, be an independent prognostic predictor for CRC, as well as a potential therapeutic target. Copyright
BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. DNA double-strand breaks (DSBs) are deleterious lesions that can lead to chromosomal anomalies, genomic instability and cancer. The histone H2AX plays an important role in response to DNA damage and phosphorylation of H2AX (p-H2AX) is evidence of DSBs. The aim of this study was to evaluate the clinical significance of p-H2AX expression in CRC. PATIENTS AND METHODS: p-H2AX expression in CRC tissues was analyzed by immunohistochemistry and correlated with clinicopathological variables using the chi-square test. The prognostic value of p-H2AX for distant metastasis-free survival (DMFS) and overall survival (OS) was evaluated by Kaplan-Meier estimates and the individual prognostic components were analyzed with Cox regression analysis. RESULTS: A high p-H2AX expression in CRC tissues was associated with tumor stage and perineurial invasion. Furthermore, a high p-H2AX expression was associated with poor DMFS and OS. Cox regression analysis also revealed that p-H2AX was an independent predictor of DMFS and OS. CONCLUSION: A high p-H2AX expression in CRC tissues is associated with a more malignant cancer behavior, as well as poor patient survival. p-H2AX may, therefore, be an independent prognostic predictor for CRC, as well as a potential therapeutic target. Copyright
Authors: Jakob Weglage; Friederike Wolters; Laura Hehr; Jakob Lichtenberger; Celina Wulz; Felix Hempel; Anne Baier; Thomas Quack; Kernt Köhler; Thomas Longerich; Gabriele Schramm; Karuna Irungbam; Heike Mueller; Verena von Buelow; Annette Tschuschner; Margarete Odenthal; Uta Drebber; Maha El Arousy; Leandra N Z Ramalho; Katrin Bankov; Peter Wild; Jörn Pons-Kühnemann; Jonas Tschammer; Christoph G Grevelding; Elke Roeb; Martin Roderfeld Journal: Sci Rep Date: 2020-12-23 Impact factor: 4.379