Identification of Phosphorylated Cyclin-Dependent Kinase 1 Associated with Colorectal Cancer Survival Using Label-Free Quantitative Analyses

Peng-Chan Lin; Yi-Fang Yang; Yu-Chang Tyan; Eric S L Hsiao; Po-Chen Chu; Chung-Ta Lee; Jenq-Chang Lee; Yi-Ming Arthur Chen; Pao-Chi Liao

doi:10.1371/journal.pone.0158844

Identification of Phosphorylated Cyclin-Dependent Kinase 1 Associated with Colorectal Cancer Survival Using Label-Free Quantitative Analyses

PLoS One. 2016 Jul 6;11(7):e0158844. doi: 10.1371/journal.pone.0158844. eCollection 2016.

Authors

Peng-Chan Lin¹, Yi-Fang Yang², Yu-Chang Tyan^{3

4

5

6}, Eric S L Hsiao², Po-Chen Chu⁷, Chung-Ta Lee⁸, Jenq-Chang Lee⁹, Yi-Ming Arthur Chen^{4

6}, Pao-Chi Liao²

Affiliations

¹ Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵ Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
⁶ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁸ Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁹ Department of Surgery, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Abstract

Colorectal cancer is the most common form of cancer in the world, and the five-year survival rate is estimated to be almost 90% in the early stages. Therefore, the identification of potential biomarkers to assess the prognosis of early stage colorectal cancer patients is critical for further clinical treatment. Dysregulated tyrosine phosphorylation has been found in several diseases that play a significant regulator of signaling in cellular pathways. In this study, this strategy was used to characterize the tyrosine phosphoproteome of colorectal cell lines with different progression abilities (SW480 and SW620). We identified a total of 280 phosphotyrosine (pTyr) peptides comprising 287 pTyr sites from 261 proteins. Label-free quantitative analysis revealed the differential level of a total of 103 pTyr peptides between SW480 and SW620 cells. We showed that cyclin-dependent kinase I (CDK1) pTyr15 level in SW480 cells was 3.3-fold greater than in SW620 cells, and these data corresponded with the label-free mass spectrometry-based proteomic quantification analysis. High level CDK1 pTyr15 was associated with prolonged disease-free survival for stage II colorectal cancer patients (n = 79). Taken together, our results suggest that the CDK1 pTyr15 protein is a potential indicator of the progression of colorectal cancer.

MeSH terms

Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Blotting, Western
CDC2 Protein Kinase / metabolism*
Cell Line, Tumor
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism*
Colorectal Neoplasms / therapy
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Neoplasm Staging
Phosphopeptides / metabolism
Phosphoproteins / metabolism*
Phosphotyrosine / metabolism
Prognosis
Proteome / metabolism*
Proteomics / methods*
Retrospective Studies

Substances

Biomarkers, Tumor
Phosphopeptides
Phosphoproteins
Proteome
Phosphotyrosine
CDC2 Protein Kinase

Grants and funding

This study was supported by grants from the National Cheng Kung University, Taiwan (NCKUH-10105014); the Ministry of Science and Technology, Taiwan (MOST 103-2811-M-006 -021,103-2113-M-006-003-MY3, 100-2113-M-006-002-MY3, 102-2352-B-006-003); the National Science Council, Taiwan (NSC 99-2923-M-006-001); and Kaohsiung Medical University, Aim for the Top 500 Universities grant and Aim for the Top Universities Grant, No. KMU-TP104E12.