Elevated tumor expression of Astroprincin (FAM171A1) is an independent marker of poor prognosis in colon cancer

Tuomas Kaprio,Alexander M Lindström,Leif C Andersson,Tiina Rasila,Olga Saavalainen,Caj Haglund,Harri Mustonen,Ines Beilmann-Lehtonen

doi:10.1186/s12876-021-01918-y

Tuomas Kaprio, Alexander M Lindström + Show 6 more

Open Access

https://doi.org/10.1186/s12876-021-01918-y

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Abstract

BackgroundColon cancer (CC) is one of the most commonly diagnosed malignancies worldwide. Several biomarkers have been suggested for improved prognostic evaluation, but few have been implemented in clinical practice. There is a need for biomarkers that predict the tumor behavior in CC and allow stratification of patients that would benefit from adjuvant therapy. We recently identified and functionally characterized a previously unknown protein that we called ASTROPRINCIN (APCN) due to its abundance in astrocytes. APCN, also annotated as FAM171A1, is found in trophoblasts of early placenta. We demonstrated that high expression levels of APCN in cancer cells induced motility and ability of invasive growth in semisolid medium.MethodsWe screened by immunohistochemistry a tissue microarray material from the tumors of 429 CC patients with clinical follow-up in a test series and 255 CC patients in a validation series.ResultsWe showed that low or absent APCN expression correlates with a favorable prognosis while high APCN expression was a sign of an adverse outcome. Cox uni- and multivariable analysis revealed that elevated tumor expression of APCN constitutes a robust marker of poor prognosis independent of stage, grade, patient’s age, or gender.ConclusionOur findings demonstrate that APCN is a novel independent prognostic marker in CC and could potentially select patients for more intense postoperative adjuvant treatment and follow-up.

Highlights

Colon cancer (CC) is one of the most commonly diagnosed malignancies worldwide
We found high expression in brain astrocytes we called the protein ASTROPRINCIN (APCN)
Three 1.0-mm-diameter punches were taken from each tumor block with a semiautomatic tissue microarray instrument (TMA) (Beecher Instruments, Silver Spring, MD) for the test series and two 1.0 mm punches for the validation series

Summary

Introduction

Colon cancer (CC) is one of the most commonly diagnosed malignancies worldwide. There is a need for biomarkers that predict the tumor behavior in CC and allow stratification of patients that would benefit from adjuvant therapy. Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies. With an estimated incidence of over 1.4 million and almost 700,000 deaths occurring worldwide CRC is the third most common cancer among. Radical surgical, and adjuvant therapy are important to clinical outcome. The stage of disease at diagnosis is the most important factor today for predicting patient outcome; roughly 40% of patients present with localized disease and another 40% present with regional disease [1]. Adjuvant therapy, resulting in a 10% absolute disease-specific survival benefit [3], is routine practice for stage III CRC patients.

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