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Elevated cleaved caspase-3 is associated with shortened overall survival in several cancer types

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机构: [1]Laboratory of Genetics, West China Institute of Women and Children’s Health, West China Second UniversityHospital, Sichuan University, Chengdu 610041, China [2]Laboratory of Cell and Gene Therapy, West China Instituteof Women and Children’s Health, West China Second University Hospital, Sichuan University, Chengdu 610041,China [3]Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University,Chengdu 610041, China [4]Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects ofMinistry of Education, Chengdu 610041, China [5]Department of Pathology, West China Hospital of Sichuan University,#37 Guoxue Street, Chengdu, Sichuan 610041, China [6]Department of Obstetric and Gynecologic, HenanProvincial People’s Hospital, Zhengzhou, Henan 450003, China [7]Department of Gynecological Oncology, SecondPeople’s Hospital of Sichuan (Sichuan Cancer Hospital), Chengdu, Sichuan 610041, People’s Republic of China
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关键词: Cleaved caspase-3 expression Multivariate Cox proportional hazards model analysis Overall survival of cancer patients Prognosis

摘要:
Emerging evidence has indicated that apoptotic cells have a compensatory effect on the proliferation of neighboring cells. Recent studies have shown that apoptotic tumor cells stimulate the repopulation of tumors from a small number of surviving cells by cleaved caspase-3 regulation and elevated tumor cleaved (and thus activated) caspase-3 expression levels predict worse treatment outcomes in cancer patients. The prognostic significance of cleaved caspase-3 should be demonstrated in more human cancer types and larger subjects. Here, we examined the cleaved caspase-3 expression in 367 human tumor samples (gastric cancer: 97 cases, ovarian cancer: 65 cases, cervical cancer: 104 cases; colorectal cancer: 101 cases) with immunohistochemistry (IHC) and the relationship between the expression of cleaved caspase-3 and various clinicopathological factors were also detected. We found that, cleaved caspase-3 was significantly associated with pathological risk factors (P < 0.005) for the studied cancers, such as tumor stage, lymph-node metastasis, differentiation and so on. In univariate and multivariate analysis, patients with high expression of cleaved caspase-3 had a significant shorter overall survival time compared with those with low cleaved caspase-3 expression in gastric cancer (P < 0.001), ovarian cancer (P < 0.001), cervical cancer (P = 0.002), colorectal cancer (P < 0.001) individually and in the patients combined (P < 0.001). Cox regression results suggested cleaved caspase-3 as an independent prognosis predictor for the studied four cancer types. Our study showed cleaved caspase-3 was well correlated to progression, aggressive behaviors in the studied cancer, and implicated it as a potential predictive factor for the prognosis of the four cancer types. It also indicated cleaved caspase-3 as a potential therapeutic target for cancer patients.

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出版当年[2014]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学 4 区 病理学
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第一作者机构: [1]Laboratory of Genetics, West China Institute of Women and Children’s Health, West China Second UniversityHospital, Sichuan University, Chengdu 610041, China [2]Laboratory of Cell and Gene Therapy, West China Instituteof Women and Children’s Health, West China Second University Hospital, Sichuan University, Chengdu 610041,China [3]Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University,Chengdu 610041, China [4]Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects ofMinistry of Education, Chengdu 610041, China
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通讯机构: [1]Laboratory of Genetics, West China Institute of Women and Children’s Health, West China Second UniversityHospital, Sichuan University, Chengdu 610041, China [2]Laboratory of Cell and Gene Therapy, West China Instituteof Women and Children’s Health, West China Second University Hospital, Sichuan University, Chengdu 610041,China [3]Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University,Chengdu 610041, China [4]Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects ofMinistry of Education, Chengdu 610041, China [*1]Laboratory of Cell and Gene Therapy, West China Institute of Women and Children’s Health, West China Second University Hospital, Sichuan University, Chengdu 610041, China [*2]Laboratory of Genetics, West China Institute of Women and Children’s Health, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
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