The Role of Circulating CD16

Hindawi Disease Markers Volume 2019, Article ID 7152183, 5 pages https://doi.org/10.1155/2019/7152183 Research Article The Role of Circulating CD16+CD56+ Natural Killer Cells in the Screening, Diagnosis, and Staging of Colorectal Cancer before Initial Treatment Feng Cui , Di Qu , Ruya Sun, Han Tao , Junru Si , and Yuqing Xu Department of Oncology, 2nd Affiliated Hospital of Harbin Medical University, China Correspondence should be addressed to Feng Cui; Received 21 June 2019; Accepted 31 July 2019; Published 17 September 2019 Guest Editor: Zhongjie Shi Copyright © 2019 Feng Cui et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background and Objective. A reliable noninvasive prediction tool for the screening, diagnosis, and/or staging of colorectal cancer (CRC) before surgery is critical for the choice of treatment and prognosis. Methods. Patients admitted for initial treatment of CRC between January 1, 2015, and December 31, 2018, were retrieved and reviewed. Records of CD16+CD56+ natural killer (NK) cells were analyzed according to the stages of CRC. Results. The number of qualified participants in the healthy, stage I, stage II, stage III, and stage IV CRC patients were 60, 66, 60, 70, and 68, respectively. There was a significant difference in circulating CD16+CD56+ NK cells between the healthy group and the CRC group (p < 0 01), as well as between the healthy group and stage III or IV CRC group (p < 0 01 and 0.001, respectively). The percentage of circulating CD16+CD56+ NK cells in lymphocytes was negatively correlated with the occurrence of CRC. When comparing the pool of stage I and II CRC cases with the pool of stage III and IV CRC cases using circulating CD16+CD56+ NK cells, the area under the Receiver Operating Characteristic curve was 0.878. Using an optimal cutoff value of 15.6%, the OR was 0.06 (0.03, 0.11), p < 0 001, sensitivity was 86.5%, specificity was 72.5%, positive predictive value was 74.2%, and negative predictive value was 85.5%. Conclusions. Circulating CD16+CD56+ NK cells can be used as a screening and diagnostic/staging tool for CRC. 1. Introduction Colorectal cancer (CRC) has an incidence of about one million per year and causes the death of nearly 700,000 people each year, ranking it the fourth most deadly cancer in the world [1, 2]. The present screening strategy of CRC is faced with low sensitivity and/or specificity in stool-based tests [3], tedious bowel preparation steps before radiographic exams, and high risk of perforation in endoscopic exams [4]. In fact, the best screening and follow-up test with high compliance for CRC should be easily completed and repeated, especially considering the up to 25% unresectable cases at the time of diagnosis and 50% recurrence rate in early-stage cases following surgery [5]. The staging and prognosis of CRC rely mainly on pathology after surgical procedures [6]. A consensus immunoscore on paraffin sections for the classification and prognosis of CRC was a practical example [7]. Although several studies have employed complementary and noninvasive biomarkers in the diagnosis of CRC [8], a reliable prediction tool with high sensitivity as well as specificity for the diagnosis and/or staging of CRC before surgery is still lacking. The immune system is known to be involved in the development and progression of CRC [9]. Immune infiltration of different immune cells in CRC has been shown to be related to metastasis and prognosis [10]. Furthermore, the circulating immune cells may reflect the local immune response in the tumor microenvironment [11], thereby providing potentially important information regarding disease progression in CRC [12]. Natural killer (NK) cells, as an important subset of the immune cells, whose activity is triggered by an evolving and delicate equilibrium between activating and inhibitory signals received by cell surface receptors, are considered interesting targets for translational and clinical studies [13]. In the present study, we analyzed CD16 and CD56 double positive NK cells in the healthy and different stages of 2 Disease Markers Table 1: Clinical characteristics of enrolled participants. Healthy control (n = 60) Stage I (n = 66) Stage II (n = 60) Stage III (n = 70) Stage IV (n = 68) p value Age (years) 34 0.50$$ 54 2 ± 3 5 36 0.81 56 0 ± 11 4 30 0.446 54 5 ± 10 3 39 0.91 56 1 ± 10 0 32 0.28 53 2 ± 15 4 0.40# — 0.49∗ p value∗∗ 0.63$$ 0.25 0.83 0.17 0.59 — Body weight (kg) 66 8 ± 11 1 70 0 ± 13 1 67 5 ± 7 2 67 3 ± 7 4 67 1 ± 16 1 0.53∗ p value∗∗ 0.48$$ 0.15 0.67 0.77 0.74 — Height (cm) 168 9 ± 8 2 169 5 ± 8 9 168 0 ± 5 4 167 6 ± 6 9 170 0 ± 9 3 0.40∗ p value∗∗ 0.89$$ 0.72 0.48 0.31 0.45 — 24 0 ± 3 0 24 3 ± 3 8 24 0 ± 2 7 23 4 ± 3 5 23 5 ± 2 9 0.37∗ 0.56$$ 0.65 0.94 0.27 0.39 — 19 2 ± 5 8 20 7 ± 11 1 21 0 ± 11 2 15 7 ± 8 5 14 7 ± 7 1 <0.001∗ <0.01$$ 0.38 0.28 <0.01 <0.001 — Cases Male p value$ BMI p value∗∗ Total NK cells (% in lymphocytes) p value∗∗ χ test among all groups. ∗ ANOVA test among all groups. $χ2 test between the healthy control group and the other corresponding groups. ∗∗ t-test between the healthy control group and the other corresponding groups. $$p value of healthy vs. CRC cases, χ2 test or t-test. # 2 CRC patients before initial treatment, trying to figure out the value of CD16+CD56+ NK cells in the prediction and pretreatment staging of CRC. ROC curve 1.0 0.8 This was a retrospective cohort study conducted at the 2nd Affiliated Hospital of Harbin Medical University, a tertiary hospital in Northeast China. Institutional Ethics Committee approval was obtained before data collection, and informed consent was obtained from patients on admission. Clinical records of patients who were admitted for initial treatment of CRC between January 1, 2015, and December 31, 2018, to the Department of Oncology were retrieved and reviewed. Included patients should have pretreatment NK cell data available (the most recent one before the first surgery), as well as histologically confirmed primary CRC. Staging was based on the Tumor Node Metastasis (TNM) terminology [14]. Patients with unclear diagnosis, complicated with other cancers, were admitted after previous treatments for CRC, with other chronic diseases (such as cardiovascular diseases and endocrine diseases), or with viral or bacterial infections were excluded. Age- and BMI-matched healthy participants (no clinical complain who just completed annual physical exam at the time of enrollment) were enrolled in the control group. Fasting peripheral venous blood samples were collected from all participants before treatment (for the CRC group) or on the day of the annual exam (for healthy controls) in a heparin-coated tube and kept at 2-8°C. 100 μl of freshly collected blood was transferred int (...truncated)