J Cancer 2021; 12(17):5144-5152. doi:10.7150/jca.53983 This issue

Research Paper

Identification of Cysteine Protease Inhibitor CST2 as a Potential Biomarker for Colorectal Cancer

Qiurong Xie1,2*, Liya Liu1,2*, Xiaoping Chen1,2, Ying Cheng1,2, Jiapeng Li1,2,3, Xiuli Zhang1,2, Nanhui Xu1,2, Yuying Han1,2, Huixin Liu1,2, Lihui Wei1,2, Jun Peng1,2✉, Aling Shen1,2✉

1. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian 350122, China.
2. Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian 350122, China.
3. Department of Physical Education, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian 350122, China.
* Q Xie and L Liu contributed equally to this work.

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Citation:
Xie Q, Liu L, Chen X, Cheng Y, Li J, Zhang X, Xu N, Han Y, Liu H, Wei L, Peng J, Shen A. Identification of Cysteine Protease Inhibitor CST2 as a Potential Biomarker for Colorectal Cancer. J Cancer 2021; 12(17):5144-5152. doi:10.7150/jca.53983. Available from https://www.jcancer.org/v12p5144.htm

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Abstract

Graphic abstract

Additional biomarkers for the development and progression of colorectal cancer (CRC) remain to be identified. Hence, the current study aimed to identify potential diagnostic markers for CRC. Analyses of cysteine protease inhibitor [cystatins (CSTs)] expression in CRC samples and its correlation with cancer stage or survival in patients with CRC demonstrated that CRC tissues had greater CST1 and CST2 mRNA expression compared to noncancerous adjacent tissues, while higher CST2 mRNA expression in CRC tissues was correlated with advanced stages and disease-free survival in patients with CRC, encouraging further exploration on the role of CST2 in CRC. Through an online database search and tissue microarray (TMA), we confirmed that CRC samples had higher CST2 expression compared to noncancerous adjacent tissue or normal colorectal tissues at both the mRNA and protein levels. TMA also revealed that colorectal adenoma, CRC, and metastatic CRC tissues exhibited a significantly increased CST2 protein expression. Accordingly, survival analysis demonstrated that the increase in CST2 protein expression was correlated with shorter overall survival of patients with CRC. Moreover, our results found a significant upregulation of CST2 in multiple cancer tissues. Taken together, these findings suggest the potential role of CST2 as a diagnostic and prognostic biomarker for CRC.

Keywords: Colorectal cancer, CST2, Tissue microarray, Oncogene, Biomarker