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Int J Clin Exp Pathol. 2014 Jul 15;7(8):5057-70. eCollection 2014.

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

Author information

1
Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University Chengdu 610041, China ; 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 ; Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University Chengdu 610041, China ; Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education Chengdu 610041, China.
2
Department of Pathology, West China Hospital of Sichuan University #37 Guoxue Street, Chengdu, Sichuan 610041, China.
3
Department of Obstetric and Gynecologic, Henan Provincial People's Hospital Zhengzhou, Henan 450003, China.
4
Department of Gynecological Oncology, Second People's Hospital of Sichuan (Sichuan Cancer Hospital) Chengdu, Sichuan 610041, People's Republic of China.
5
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 ; Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University Chengdu 610041, China ; Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education Chengdu 610041, China.
6
Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University Chengdu 610041, China ; Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University Chengdu 610041, China ; Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education Chengdu 610041, China.

Abstract

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.

KEYWORDS:

Cleaved caspase-3 expression; multivariate Cox proportional hazards model analysis; overall survival of cancer patients; prognosis

PMID:
25197379
PMCID:
PMC4152069
[Indexed for MEDLINE]
Free PMC Article

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