Prolyl 4-hydroxylase alpha 1 protein expression risk-stratifies early stage colorectal cancer
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Atsushi Tanaka1,2,3, Yihua Zhou1,3,4, Jinru Shia1, Fiona Ginty5, Makiko Ogawa1,3, David S. Klimstra1, Ronald C. Hendrickson6, Julia Y. Wang7 and Michael H. Roehrl1,3
1 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
2 Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
3 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
4 ICU Department, Second Affiliated Hospital of Nanchang University, Nanchang, China
5 GE Global Research Center, Niskayuna, NY, USA
6 Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
7 Curandis, New York, NY, USA
|Michael H. Roehrl,||email:||[email protected]|
Keywords: P4HA1; colorectal cancer; biomarker; prognosis; pathology
Abbreviations: CRC: colorectal cancer; IHC: immunohistochemistry; LC-MS: liquid chromatography-mass spectrometry; DFS: disease-free survival; OS: overall survival
Received: December 21, 2019 Accepted: January 30, 2020 Published: February 25, 2020
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.
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