title: Elevated cleaved caspase-3 is associated with shortened overall survival in several cancer types.
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.
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Pathology, West China Hospital of Sichuan University #37 Guoxue Street, Chengdu, Sichuan 610041, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Obstetric and Gynecologic, Henan Provincial People's Hospital Zhengzhou, Henan 450003, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Gynecological Oncology, Second People's Hospital of Sichuan (Sichuan Cancer Hospital) Chengdu, Sichuan 610041, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Xinlian
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Hongqian
authors.initials: H
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Shanling
authors.initials: S
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: He
authors.initials: H
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis*; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D053148:Caspase 3
keywords: Cleaved caspase-3 expression; multivariate Cox proportional hazards model analysis; overall survival of cancer patients; prognosis