Reduced plasma level of CXC chemokine ligand 7 in patients with pancreatic cancer.

Abstract

BACKGROUND:

Early detection is essential to improve the outcome of patients with pancreatic cancer. A noninvasive and cost-effective diagnostic test using plasma/serum biomarkers would facilitate the detection of pancreatic cancer at the early stage.

METHODS:

Using a novel combination of hollow fiber membrane-based low-molecular-weight protein enrichment and LC-MS-based quantitative shotgun proteomics, we compared the plasma proteome between 24 patients with pancreatic cancer and 21 healthy controls (training cohort). An identified biomarker candidate was then subjected to a large blinded independent validation (n = 237, validation cohort) using a high-density reverse-phase protein microarray.

RESULTS:

Among a total of 53,009 MS peaks, we identified a peptide derived from CXC chemokine ligand 7 (CXCL7) that was significantly reduced in pancreatic cancer patients, showing an area under curve (AUC) value of 0.84 and a P value of 0.00005 (Mann-Whitney U test). Reduction of the CXCL7 protein was consistently observed in pancreatic cancer patients including those with stage I and II disease in the validation cohort (P < 0.0001). The plasma level of CXCL7 was independent from that of CA19-9 (Pearson's r = 0.289), and combination with CXCL7 significantly improved the AUC value of CA19-9 to 0.961 (P = 0.002).

CONCLUSIONS:

We identified a significant decrease of the plasma CXCL7 level in patients with pancreatic cancer, and combination of CA19-9 with CXCL7 improved the discriminatory power of the former for pancreatic cancer.

IMPACT:

The present findings may provide a new diagnostic option for pancreatic cancer and facilitate early detection of the disease.

• Authors: Junichi Matsubara, Kazufumi Honda, Masaya Ono, Yoshinori Tanaka, Michimoto Kobayashi, Giman Jung, Koji Yanagisawa, Tomohiro Sakuma, Shoji Nakamori, Naohiro Sata, Hideo Nagai, Tatsuya Ioka, Takuji Okusaka, Tomoo Kosuge, Akihiko Tsuchida, Masashi Shimahara, Yohichi Yasunami, Tsutomu Chiba, Setsuo Hirohashi, Tesshi Yamada
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 20 Issue 1 Pg. 160-71 (Jan 2011) ISSN: 1538-7755 [Electronic] United States
• PMID: 21148121 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2011 AACR.

Chemical References

• Biomarkers, Tumor
• CA-19-9 Antigen
• PPBP protein, human
• beta-Thromboglobulin

Topics

• Adult
• Aged
• Biomarkers, Tumor (blood)
• CA-19-9 Antigen (blood)
• Case-Control Studies
• Chromatography, Liquid
• Female
• Humans
• Male
• Mass Spectrometry
• Middle Aged
• Pancreatic Neoplasms (blood, diagnosis)
• Prospective Studies
• Reproducibility of Results
• beta-Thromboglobulin (analysis, metabolism)