Lin Runhua, Xiao Dejun, Guo Yi, Tian Dongping, Yun Hailong, Chen Donglin, Su Min
Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, PR China.
The Judicial Critical Center, Shantou University Medical College, Shantou, Guangdong, PR China.
Oncotarget. 2015 Feb 20;6(5):2856-64. doi: 10.18632/oncotarget.3091.
Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia.
贲门癌（GCC）是一种与慢性炎症相关的侵袭性很强的疾病。为了研究DNA损伤反应（DDR）与慢性炎症之间的关系，我们收集了100份来自食管癌和贲门癌高发区潮汕沿海地区的非肿瘤贲门胃标本。与非发育异常组织（40.7%）相比，发育异常上皮中严重慢性炎症的比例显著更高（80.9%）（P<0.001）。免疫组织化学分析表明，DNA损伤反应与从正常炎症到严重炎症的慢性炎症程度呈平行关系（P<0.05）。我们发现，DNA损伤反应随着癌前病变的进展而逐渐增加（P<0.05）。这些发现提供了病理学证据，即持续的慢性炎症相关DNA损伤反应可能是贲门癌发生的驱动力。基于这些发现，非恶性组织中的DNA损伤反应可能成为预测贲门恶性转化的有前景的生物医学标志物。
