Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation

胰腺癌患者血浆载脂蛋白修饰改变:蛋白质表征和多机构验证

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作者:Kazufumi Honda, Takuji Okusaka, Klaus Felix, Shoji Nakamori, Naohiro Sata, Hideo Nagai, Tatsuya Ioka, Akihiko Tsuchida, Takeshi Shimahara, Masashi Shimahara, Yohichi Yasunami, Hideya Kuwabara, Tomohiro Sakuma, Yoshihiko Otsuka, Norihito Ota, Miki Shitashige, Tomoo Kosuge, Markus W Büchler, Tesshi Ya

Background

Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection.

Conclusions

We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.

Methods

We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1) using a newly developed matrix-assisted laser desorption/ionization (oMALDI) QqTOF (quadrupole time-of-flight) mass spectrometry (MS) system.

Results

We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z), unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z), and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21), P = 4.35×10(-14), and P = 1.83×10(-24) (Mann-Whitney U-test); area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103) and Cohort 3 (n = 163)] and a prospective cohort [Cohort 4 (n = 833)] collected from 8 medical institutions in Japan and Germany. Conclusions: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.

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