Synergistic role of Caspase-8 and Caspase-3 expressions: Prognostic and predictive biomarkers in colorectal cancer

Article type: Research Article

Authors: Yao, Qiang^{a; b; 1} | Wang, Weimin^{a; c; 1} | Jin, Jun^{a; 1} | Min, Ke^a | Yang, Jian^a | Zhong, Yubing^d | Xu, Chunni^a | Deng, Jianliang^{a; *} | Zhou, Yan^{a; c; *}

Affiliations: [a] Department of Oncology, Yixing Hospital Affiliated to Medical College of Yangzhou University, Yixing, Jiangsu, China | [b] Department of Oncology, The Second Affiliated Hospital of Soochow University, Soochow, Jiangsu, China | [c] Institute of Combining Chinese Traditional and Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, China | [d] Department of General Surgery, Yixing Hospital Affiliated to Medical College of Yangzhou University, Yixing, Jiangsu, China

Correspondence: [*] Corresponding authors: Yan Zhou and Jianliang Deng, Department of Oncology, Yixing Hospital Affiliated to Medical College of Yangzhou University, Yixing, Jiangsu, China. E-mail: dryzhou@163.com;staff804@yxph.com.

Note: [1] Equal contributors.

Abstract: BACKGROUND: Expressions of Caspase-8 and Caspase-3 have been identified as important markers in many malignant tumors, but their roles in colorectal cancer (CRC) have not been confirmed. The purpose of this study was to investigate the role of Caspase-8 and Caspase-3 in CRC. METHODS: We enrolled 470 CRC patients in this study. Archival paraffin-embedded CRC tissue samples were used to construct tissue microarray (TMA), expressions of Caspase-8 and Caspase-3 that were stained by immunohistochemistry. Prognostic and predictive role of Caspase-8 and Caspase-3 expressions, alone or united, were evaluated by univariate and multivariate analysis respectively. RESULTS: In comparison with adjacent normal tissues, Caspase-8 and Caspase-3 protein levels were upregulated in CRC tissues significantly, furthermore, high expressions of Caspase-8 and Caspase-3 were correlated with decreased overall survival (OS) (p< 0.05), and also with unfavorable clinicopathologic characteristics. Cox regression analysis showed that high Caspase-8 and Caspase-3 expressions were independent negative markers of OS. CONCLUSION: Caspase-8 and Caspase-3 expressions in tumor tissues are novel candidate prognostic markers for CRC patients. It was the first time to be identified that Caspase-8 and Caspase-3 expressions had synergistic role as efficient prognostic indicators for CRC patients.

Keywords: Caspase-8, Caspase-3, colorectal cancer (CRC), diagnosis, prognosis

DOI: 10.3233/CBM-170967

Journal: Cancer Biomarkers, vol. 21, no. 4, pp. 899-908, 2018