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Reduced plasma lever 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.

Credits:

Junichi Matsubara1,2, Kazufumi Honda1, Masaya Ono1, Yoshinori Tanaka3, Michimoto Kobayashi3, Giman Jung3, Koji Yanagisawa4, Tomohiro Sakuma4, Shoji Nakamori5, Naohiro Sata6, Hideo Nagai6, Tatsuya Ioka7, Takuji Okusaka8, Tomoo Kosuge8, Akihiko Tsuchida9, Masashi Shimahara10, Yohichi Yasunami11, Tsutomu Chiba2, Setsuo Hirohashi1 and Teshi Yamada1

  • 1. Chemotherapy Division, National Cancer Center Research Institute, Tokyo
  • 2. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto
  • 3. New Frontiers Research Laboratories, Toray Industries Kamakura
  • 4. BioBusiness Group, Mitsui Knowledge Industry Tokyo
  • 5. Department of Surgery, Osaka National Hospital, National Hospital Organization, Osaka
  • 6. Department of Surgery, Jichi Medical University, Shimotsuke
  • 7. Department of Hepatobiliary and Pancratic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka
  • 8. Hepatobiliary and Pancreatic Oncology and Hepatobiliary and Pancreatic Surgery Divisions, National Cancer Center Hospital, Tokyo
  • 9. Third Department of Surgery, Tokyo Medical University, Tokyo
  • 10. Department of Oral Surgery, Osaka Medical College, Osaca
  • 11. Department of Regenerative Medicine and Transplantation, Fukuoka University Faculty of Medicine, Fukuoka, Japan

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