Identification of aldolase A as a potential diagnostic biomarker for colorectal cancer based on proteomic analysis using formalin-fixed paraffin-embedded tissue.

Tetsushi Yamamoto,Kiyoshi Teduka,Wei-Xia Peng,Mitsuhiro Kudo,Atsushi Taga,Takenori Fujii,Kuniko Mitamura,Zenya Naito,Eiji Uchida,Hideyuki Takata,Hideki Takakura

doi:10.1007/s13277-016-5275-8

Tetsushi Yamamoto, Kiyoshi Teduka + Show 9 more

Open Access

https://doi.org/10.1007/s13277-016-5275-8

Copy DOI

Journal: Tumor Biology	Publication Date: Jul 28, 2016
Citations: 42	License type: CC BY 4.0

Affiliation: Kindai University, Nippon Medical School

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide, and many patients are already at an advanced stage when they are diagnosed. Therefore, novel biomarkers for early detection of colorectal cancer are required. In this study, we performed a global shotgun proteomic analysis using formalin-fixed and paraffin-embedded (FFPE) CRC tissue. We identified 84 candidate proteins whose expression levels were differentially expressed in cancer and non-cancer regions. A label-free semiquantitative method based on spectral counting and gene ontology (GO) analysis led to a total of 21 candidate proteins that could potentially be detected in blood. Validation studies revealed cyclophilin A, annexin A2, and aldolase A mRNA and protein expression levels were significantly higher in cancer regions than in non-cancer regions. Moreover, an in vitro study showed that secretion of aldolase A into the culture medium was clearly suppressed in CRC cells compared to normal colon epithelium. These findings suggest that decreased aldolase A in blood may be a novel biomarker for the early detection of CRC.

Highlights

Colorectal cancer (CRC) is one of the most common cancers worldwide
To investigate the molecular profile of proteins expressed in relation to cancer progression, we performed shotgun proteomic analysis using Formalin-fixed and paraffin-embedded (FFPE) CRC tissue
To identify early detection markers for CRC that can be detected by diagnostic blood tests, we focused on proteins in the Bextracellular region^ category of cellular components based on the results of gene ontology (GO) analysis (Table 4)

Summary

Introduction

Colorectal cancer (CRC) is one of the most common cancers worldwide. If the tumor is limited to the mucosa or submucosa, CRC can be completely cured by endoscopic or surgical therapy; many patients are already at an advanced stage when they are diagnosed. Diagnostic blood tests based on detection of carcinoembryonic antigen (CEA) are widely used for CRC, but the sensitivity of this biomarker in early-stage cancer is only 5–10 % [1, 2]. The identification of novel candidate molecules that are secreted by cancer cells may lead to the development of early detection methods and improved prognosis. FFPE tissues are routinely used in the diagnosis and research of diseases, including cancers, by conventional staining, immunohistochemistry (IHC), and in situ hybridization [3,4,5]. Archived FFPE tissues may be useful for identifying new biomarkers

Methods

Results

Discussion

Conclusion