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Int J Cancer. 2019 Jan 17. doi: 10.1002/ijc.32137. [Epub ahead of print]

β6 -integrin serves as a novel serum tumor marker for colorectal carcinoma.

Author information

1
Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
2
Department of Immunology, Stanford University, Stanford, CA.
3
National Center for Cancer Care and Research NCCCR, Hamad Medical Corporation, Doha, Qatar.
4
Cancer and Translational Medicine Research Unit, Department of Pathology, University of Oulu, Oulu, Finland.
5
Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.
6
Department of Gastroenterology, University Hospital, Basel, Switzerland.
7
Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland.
8
Department of Pathology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
9
Clinic for Gastroenterology Bethanien, Zürich, Switzerland.
10
Clinic for Gastroenterology Zurich-Fluntern, Zurich, Switzerland.
11
Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom.
12
Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA.
13
Department of Surgery, University Hospital Magdeburg, Magdeburg, Germany.
14
Department of Medical Informatics, University of Erlangen-Nuremberg, Erlangen, Germany.
15
Division of Molecular and Experimental Surgery, University Medical Center Erlangen, Erlangen, Germany.
16
Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β6 -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.

KEYWORDS:

ITGB6; colorectal cancer; metastasis; serum tumor marker; surveillance; therapy response

PMID:
30653264
DOI:
10.1002/ijc.32137

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