Research Papers:

The levels of serine proteases in colon tissue interstitial fluid and serum serve as an indicator of colorectal cancer progression

Yingying Xie, Lechuang Chen, Xiaolei Lv, Guixue Hou, Yang Wang, Cuicui Jiang, Hongxia Zhu, Ningzhi Xu, Lin Wu, Xiaomin Lou and Siqi Liu _

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Oncotarget. 2016; 7:32592-32606. https://doi.org/10.18632/oncotarget.8693

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Yingying Xie1,2, Lechuang Chen3, Xiaolei Lv4, Guixue Hou1,2, Yang Wang1,2, Cuicui Jiang4, Hongxia Zhu3, Ningzhi Xu3, Lin Wu1,2, Xiaomin Lou1,2, Siqi Liu1,2,4,5

1CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China

2University of Chinese Academy of Sciences, Beijing, 100049, China

3Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

4Beijing Protein Innovation, Beijing, 101318, China

5Proteomics Division, BGI-Shenzhen, Shenzhen, Guangdong, 518083, China

Correspondence to:

Lin Wu, email: [email protected]

Xiaomin Lou, email: [email protected]

Siqi Liu, email: [email protected]

Keywords: tissue interstitial fluid, serum, colorectal cancer, biomarker, serine proteases

Received: January 27, 2016     Accepted: March 28, 2016     Published: April 11, 2016


The proteins in tissue interstitial fluids (TIFs) can spread into the blood and have been proposed as an ideal material to find blood biomarkers. The colon TIFs were collected from 8-, 13-, 18-, and 22-week ApcMin/+, a typical mouse model of colorectal cancer (CRC), and wild-type mice. iTRAQ-based quantification proteomics was conducted to survey the TIF proteins whose abundance appeared to depend on tumor progression. A total of 46 proteins that exhibited consecutive changes in abundance were identified, including six serine proteases, chymotrypsin-like elastase 1 (CELA1), chymotrypsin-like elastase 2A (CEL2A), chymopasin, chymotrypsinogen B (CTRB1), trypsin 2 (TRY2), and trypsin 4 (TRY4). The observed increases in the abundance of serine proteases were supported in another quantitative evaluation of the individual colon TIFs using a multiple reaction monitor (MRM) assay. Importantly, the increases in the abundance of serine proteases were also verified in the corresponding sera. The quantitative verification of the serine proteases was further extended to the clinical sera, revealing significantly higher levels of CELA1, CEL2A, CTRL/chymopasin, and TRY2 in CRC patients. The receiver operating characteristic analysis illustrated that the combination of CELA1 and CTRL reached the best diagnostic performance, with 90.0% sensitivity and 80.0% specificity. Thus, the quantitative target analysis demonstrated that some serine proteases are indicative of CRC progression.

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