Feng Liu, Tao Lin, Dawei He, Xuliang Li, Xiaodong Luo
Department of Urinary Surgery, the Children's Hospital, Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorder, Key Laboratory of Pediatrics in Chongqing (CSTC2009CA5002), Chongqing, 400014, China.
Pathol Oncol Res. 2014 Jul;20(3):603-10. doi: 10.1007/s12253-013-9738-6. Epub 2013 Dec 28.
Regional hypoxia caused by accelerated cell proliferation and overgrowth is an important characteristic of neoplasm. Hypoxia can cause a series of changes in gene transcription and protein expression, thereby not only inducing tumor cell resistance to radiotherapy and chemotherapy but also promoting tumor invasion and metastasis. This study aimed to investigate the relationship between HIF-1α expression and cellular apoptosis, angiogenesis and clinical prognosis in rectal carcinoma. In 113 rectal carcinoma cases, cellular apoptosis was analyzed by the in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, whereas the levels of HIF-1α expression, VEGF expression, microvessel density (MVD) and lymphatic vessel density(LVD) were examined by immunohistochemical staining. HIF-1 expression was detected in 67 of 113 rectal carcinoma cases (59.3 %). A positive correlation was found among HIF-1α expression, cellular apoptosis and angiogenesis. The 5-year survival rate in the HIF-1α-negative group was significantly higher than that in the HIF-1α-positive group (81.34 % versus 50 %, P < 0.05). According to the Cox regression analysis, HIF-1α expression, VEGF expression and cellular apoptosis index were independent risk factors for clinical prognosis in rectal carcinoma. Aberrant HIF-1α expression correlates with apoptosis inhibition, angiogenesis and poor prognosis in rectal carcinoma.
细胞增殖加速和过度生长所导致的局部缺氧是肿瘤的一个重要特征。缺氧可引起基因转录和蛋白质表达的一系列变化,不仅会诱导肿瘤细胞对放疗和化疗产生抗性,还会促进肿瘤侵袭和转移。本研究旨在探讨直肠癌中HIF-1α表达与细胞凋亡、血管生成及临床预后之间的关系。在113例直肠癌病例中,采用原位末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法(TUNEL法)分析细胞凋亡情况,而通过免疫组织化学染色检测HIF-1α表达水平、VEGF表达水平、微血管密度(MVD)和淋巴管密度(LVD)。113例直肠癌病例中有67例检测到HIF-1表达(59.3%)。发现HIF-1α表达、细胞凋亡和血管生成之间呈正相关。HIF-1α阴性组的5年生存率显著高于HIF-1α阳性组(81.34%对50%,P<0.05)。根据Cox回归分析,HIF-1α表达、VEGF表达和细胞凋亡指数是直肠癌临床预后的独立危险因素。异常的HIF-1α表达与直肠癌中的凋亡抑制、血管生成及不良预后相关。