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

• Published in: International journal of clinical and experimental pathology Vol. 7; no. 8; pp. 5057 - 5070
• Main Authors: Hu, Qian, Peng, Jing, Liu, Weiping, He, Xiaoli, Cui, Ling, Chen, Xinlian, Yang, Mei, Liu, Hongqian, Liu, Shanling, Wang, He
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2014
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Apoptosis - physiology; Biomarkers, Tumor - analysis; Caspase 3 - analysis; Caspase 3 - metabolism; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Disease Progression; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms - enzymology; Neoplasms - mortality; Neoplasms - pathology; Original; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Proportional Hazards Models; Risk Factors; Stomach Neoplasms - enzymology; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Uterine Cervical Neoplasms - enzymology; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - pathology; Young Adult; Cleaved caspase-3 expression; multivariate Cox proportional hazards model analysis; prognosis; overall survival of cancer patients
• ISSN: 1936-2625; 1936-2625

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.