Membrane Proteins as Potential Colon Cancer Biomarkers: Verification of 4 Candidates from a Secretome Dataset

Sum-Fu Chiang^1,2, Ming-Hung Tsai³, Reiping Tang^1,4, Ling-Ling Hsieh⁵, Jy-Ming Chiang¹, Chien-Yuh Yeh¹, Pao-Shiu Hsieh¹, Wen-Sy Tsai¹, Ya-Ping Liu⁶, Ying Liang⁶, Jinn-Shiun Chen^1*, Jau-Song Yu^7*

¹Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, New Taipei City.
²Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan.
³Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan.
⁴College of Medicine, Chang Gung University, New Taipei City.
⁵Department of Public Health, Chang Gung University, Taoyuan.
⁶Pathology Core of the Chang Gung Molecular Medicine Research Center, Taoyuan.
⁷Department of Biochemistry and Molecular Biology, Chang Gung University, Taoyuan.

DOI: 10.4236/ss.2014.510067                

Abstract

Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are expected to improve CRC detection and management. From a colorectal cancer cell secretome database, we chose four proteins as candidates for clinical verification, including tumor-associated calcium signal transducer 2 (TROP2, TACSTD2), transmembrane 9 superfamily member 2 (TM9SF2), and tetraspanin-6 (TSPAN6), and tumor necrosis factor receptor superfamily member 16 (NGFR). Different groups of 30 CRC patients’ tissue samples collected from Chang Gung Memorial Hospital were analyzed by immunohistochemistry (IHC) for the four proteins, and the results were scored by pathologist. For all the four candidate proteins, marked differences of IHC score existed between tumor and adjacent non-tumor counterpart. However, there were only trends between higher protein expression levels and worse outcome. Three proteins (TROP2, TM9SF2 and NGFR) had trends between higher tissue expression and tumor stage or lymph node metastasis. Our study revealed that tissue expression of four proteins (TROP2, TM9SF2, TSPAN6, and NGFR) was markedly different between tumor and adjacent non-tumor counterparts. Overexpression of all these four proteins showed some trends with poorer survival.

Keywords

Biomarker, Colorectal Cancer, Immunohistochemistry, Membrane Protein, Secretome, Tetraspanin-6, Transmembrane 9 Superfamily Member 2, Tumor-Associated Calcium Signal Transducer 2, Tumor Necrosis Factor Receptor Superfamily Member 16, Verification

Conflicts of Interest

The authors declare no conflicts of interest.

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