Prolyl 4-hydroxylase alpha 1 protein expression risk-stratifies early stage colorectal cancer Journal Article


Authors: Tanaka, A.; Zhou, Y.; Shia, J.; Ginty, F.; Ogawa, M.; Klimstra, D. S.; Hendrickson, R. C.; Wang, J. Y.; Roehrl, M. H.
Article Title: Prolyl 4-hydroxylase alpha 1 protein expression risk-stratifies early stage colorectal cancer
Abstract: Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies. Especially for early stage CRC, prognostic molecular markers are needed to guide therapy. In this study, we first extracted total proteomes from matched pairs of fresh cancer and benign mucosal tissues from 22 CRC patients. Global proteomic profiling with Fourier transform liquid chromatography-mass spectrometry sequencing and label free quantitation uncovered that P4HA1 (prolyl 4-hydroxylase alpha 1) was overexpressed in CRC relative to benign colonic mucosa. We then investigated expression by immunohistochemical staining with P4HA1-specific antibodies using CRC tissue microarrays. Independent validation cohorts of 599 cases of early stage CRC and 91 cases of late stage CRC were examined. Multivariate and univariate survival analyses revealed that high expression of P4HA1 protein was an independent poor prognostic marker for patients with early stage CRC, especially of the microsatellite stable subtype. Our study provides strong support for P4HA1 as a predictive protein marker for precision diagnostics, therapeutic decision-making, and drug development for early stage colorectal cancer and demonstrates the utility of proteomic profiling to identify novel protein biomarkers. © Tanaka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: colorectal cancer; pathology; biomarker; prognosis; p4ha1
Journal Title: Oncotarget
Volume: 11
Issue: 8
ISSN: 1949-2553
Publisher: Impact Journals  
Date Published: 2020-02-25
Start Page: 813
End Page: 824
Language: English
DOI: 10.18632/oncotarget.27491
PROVIDER: scopus
PMCID: PMC7055541
PUBMED: 32166002
DOI/URL:
Notes: Article -- Export Date: 1 May 2020 -- Source: Scopus
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MSK Authors
  1. David S Klimstra
    978 Klimstra
  2. Jinru Shia
    720 Shia
  3. Michael H Roehrl
    127 Roehrl
  4. Atsushi Tanaka
    35 Tanaka
  5. Yihua Zhou
    13 Zhou
  6. Makiko Ogawa
    26 Ogawa