Chi-Wen Luo1, Jaw-Yuan Wang2, Wen-Chun Hung3, Guang Peng4, Ya-Li Tsai3, Tsung-Ming Chang3, Chee-Yin Chai1, Chih-Hung Lin1, Mei-Ren Pan5. 1. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan. 2. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Taiwan. 3. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. 4. Department of Clinical Cancer Prevention, Unit 1013, The University of Texas MD Anderson Cancer Center, Houston, USA. 5. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Taiwan. Electronic address: mrpan@cc.kmu.edu.tw.
Abstract
BACKGROUND AND PURPOSE: Neoadjuvant concurrent chemoradiotherapy (CCRT) is a standard treatment of locally advanced colon cancer cell (CRC). In order to maximize efficacy and minimize toxicity, new drugs have been developed and used in combination with CCRT. Recently, it has been shown that G9a plays a role in mediating phenotypes of cancer stem cells (CSCs). This study aimed to characterize G9a as a biomarker in predicting therapy response to prevent overtreatment and adverse effects in CRC patients. EXPERIMENTAL DESIGN: The primary tumors from 39 patients who received CCRT for rectal cancer were selected. In vivo tumor xenograft models for tumorigenic properties in immunodeficient mice were developed. In vitro stemness ability was performed by tumor-sphere assays, cell response to anti-cancer agents and stemness-related genes analysis. RESULTS: Cells survived from radiation treatment, and displayed high levels of G9a. A significantly positive correlation was shown between G9a and CSCs marker CD133 in locally advanced rectal cancer patients with CCRT. Knockdown of G9a increased the sensitivity of cells to radiation treatment and sensitized cells to DNA damage agents through PP2A-RPA axis. CONCLUSIONS: Our study theorized that G9a might serve as a novel target in colon cancer, which offers exciting potential in prediction of response to preoperative chemoradiotherapy in patients with advanced CRC.
BACKGROUND AND PURPOSE: Neoadjuvant concurrent chemoradiotherapy (CCRT) is a standard treatment of locally advanced colon cancer cell (CRC). In order to maximize efficacy and minimize toxicity, new drugs have been developed and used in combination with CCRT. Recently, it has been shown that G9a plays a role in mediating phenotypes of cancer stem cells (CSCs). This study aimed to characterize G9a as a biomarker in predicting therapy response to prevent overtreatment and adverse effects in CRC patients. EXPERIMENTAL DESIGN: The primary tumors from 39 patients who received CCRT for rectal cancer were selected. In vivo tumor xenograft models for tumorigenic properties in immunodeficientmice were developed. In vitro stemness ability was performed by tumor-sphere assays, cell response to anti-cancer agents and stemness-related genes analysis. RESULTS: Cells survived from radiation treatment, and displayed high levels of G9a. A significantly positive correlation was shown between G9a and CSCs marker CD133 in locally advanced rectal cancerpatients with CCRT. Knockdown of G9a increased the sensitivity of cells to radiation treatment and sensitized cells to DNA damage agents through PP2A-RPA axis. CONCLUSIONS: Our study theorized that G9a might serve as a novel target in colon cancer, which offers exciting potential in prediction of response to preoperative chemoradiotherapy in patients with advanced CRC.