Contents lists available at ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/cca Serum FBLN1 and STK31 as biomarkers of colorectal cancer and their ability to noninvasively differentiate colorectal cancer from benign polyps Mona Mohamed Watany a, ⁎ , Nehal Mohamed Elmashad b , Rehab Badawi c , Nehad Hawash c a Clinical Pathology Department, Faculty of Medicine, Tanta University Hospital, El-Geesh St., Tanta, Egypt b Tanta University Hospital, Clinical Oncology Department, Faculty of Medicine, El-Geesh St., Tanta, Egypt c Tanta University Hospital, Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, El-Geesh St., Tanta, Egypt ARTICLE INFO Keywords: Fibulin-1 (FBLN1) Serine/threonine kinase-31 (STK31) Colorectal cancer Tumour marker ABSTRACT Purpose: The aim of this work is to evaluate Fibulin-1 (FBLN1) and serine threonine kinase-31 (STK31) as colorectal cancer (CRC) tumour markers and their ability to differentiate it from colorectal benign lesions. Material and methods: In this case-control study, FBLN1 and STK31 serum levels were measured in 120 parti- cipants; 49 CRC patients (group I), 26 patients with benign colorectal polyps (group II) and 45 healthy controls (group III). Results: The means of serum FBLN1 were 1.02 ± 0.95, 6.36 ± 2.55 and 6.26 ± 2.76 in group I, II and III respectively. Significant lower levels were found in group I compared to group II and III (both p < 0.001) with no significant difference between group II and III (p = .983). The means of serum STK31 were 13.51 ± 7.67, 5.98 ± 3.3 and 1.37 ± 1.22 in group I, II and III respec- tively with significant differences in-between the 3 groups (p < 0.001). Both FBLN1 and STK31 were superior to CEA as CRC screening biomarkers; with sensitivity 90.1% and 93% respectively and specificity 93.9% and 95.9% respectively. FBLN1 differentiated CRC from benign polyps with 91.8% sensitivity and 100% specificity. STK31 differ- entiated CRC from benign polyps with 93.9% sensitivity and 84.6% specificity. Conclusion: FBLN1 and STK31 can be possible screening and differentiating biomarkers of CRC. 1. Introduction Colorectal cancer (CRC) is the third most common cancer and the forth among cancer related deaths worldwide [1]. The increasing in- cidence in developing countries may be attributed to the transition to Western lifestyle and unhealthy dietary habits. Obesity, smoking, fibre- deficient calorie-dense diet and the lack of physical activity markedly increase the risk for developing CRC [2]. CRC is a disease of insidious onset and invasive nature. It is usually diagnosed at advanced stages as many patients remain asymptomatic during cancer's silent progression [3]. Benign colorectal polyps are common colonoscopy finding. They are histologically classified into benign adenomas, hyperplastic polyps, hamartomas and inflammatory polyps. Benign adenomas and hyper- plastic polyps are the most common types. The risk factors for the de- velopment of colonic adenomas include genetic susceptibility and ac- quired environmental factors similar to those implicated in CRC development [4–6]. Clinically polyps remain asymptomatic till they reach large sizes and protrude into the colon lumen causing changes in the bowel habits, chronic pain and hematochezia [7]. Fibulin-1 (FBLN1) is a multi-functional secreted glycoprotein that acts as extracellular matrix (ECM) stabilizer through its interactions with other ECM proteins [8]. The interaction between malignant cells and the surrounding microenvironment has a critical role in tu- morgenesis and metastasis [9]. Fibulin-1 binds to fibronectin, fibrinogen, angiogenin, laminin-1, proteoglycans aggrecan, tropoelastin and versican, thus mediating signal transduction and modulating cell growth, mobility and inva- siveness [10]. Fibulin-1 inhibits the phosphorylation of extracellular signal-regulated kinase and myosin light chain kinase. Also, it reduces the intracellular calcium level, which is important for the activation of multiple signal cascades such as the Ras/MAPK pathway [11]. The tumour-suppressing role of FBLN1 has been described in many types of cancers like gastric carcinoma, prostate cancer and estrogen dependent cancers namely breast and ovarian cancers. However, its role in CRC is still unclear [1]. Serine/threonine kinase-31 (STK31) is a protein kinase that loca- lizes to the centrosome and is involved in the control of all cell cycle https://doi.org/10.1016/j.cca.2018.04.038 Received 21 February 2018; Received in revised form 11 April 2018; Accepted 27 April 2018 ⁎ Corresponding author. E-mail address: Mona.watany@med.tanta.edu.eg (M.M. Watany). Clinica Chimica Acta 483 (2018) 151–155 Available online 30 April 2018 0009-8981/ © 2018 Elsevier B.V. All rights reserved. T