Lee Yi-Chen, Yin Tzu Chieh, Chen Yi-Ting, Chai Chee-Yin, Wang Jaw Yuan, Liu Mei-Chi, Lin Yuan-Chien, Kan Jung Yu
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.
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.
Anticancer Res. 2015 Apr;35(4):2447-53.
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.
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.
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.
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.
背景/目的：结直肠癌（CRC）是全球癌症相关死亡的最常见原因之一。DNA双链断裂（DSB）是有害的损伤，可导致染色体异常、基因组不稳定和癌症。组蛋白H2AX在DNA损伤应答中起重要作用，H2AX的磷酸化（p-H2AX）是DSB的证据。本研究的目的是评估p-H2AX表达在结直肠癌中的临床意义。
采用免疫组织化学分析结直肠癌组织中p-H2AX的表达，并使用卡方检验将其与临床病理变量相关联。通过Kaplan-Meier估计评估p-H2AX对无远处转移生存期（DMFS）和总生存期（OS）的预后价值，并用Cox回归分析单个预后成分。
结直肠癌组织中高p-H2AX表达与肿瘤分期和神经周浸润相关。此外，高p-H2AX表达与较差的DMFS和OS相关。Cox回归分析还显示，p-H2AX是DMFS和OS的独立预测因子。
结直肠癌组织中高p-H2AX表达与更恶性的癌症行为以及患者较差的生存率相关。因此，p-H2AX可能是结直肠癌的独立预后预测因子以及潜在的治疗靶点。
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