Diagnostic rather than prognostic markers-relationship between EpCAM overexpression and lung cancer: a meta-analysis.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs). However, the diagnostic and prognostic significance of EpCAM in lung cancer remains largely undetermined. In the present study, we systematically summarized and elucidated the correlation between EpCAM overexpression and lung cancer through a meta-analysis. METHODS: Six databases (PubMed, Web of Science, Cochrane Library, and Embase, CnKI and Wanfang Database) were systematically searched. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria were adopted to assess the qualities of the included studies. Relevant data were extracted for meta-analysis using the Stata12.0 software. Unadjusted mixed odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (95% CI) were estimated to evaluate the correlation between EpCAM overexpression and lung cancer. The sensitivity and specificity of the included studies were used to construct the summary receiver operator characteristic (SROC) curve and calculate the area under the SROC curve (AUC). RESULTS: A total of 14 studies consisting of 2,658 lung cancer patients were included following the PICOS principle. We found that the EpCAM expression was significantly higher in lung cancer patients compared with normal controls, including patients with benign pulmonary diseases (OR =63.71, 95% CI, 14.59-278.21, P=0.003) and healthy individuals (OR =520.08, 95% CI, 16.38-16,510.80, P=0.002), and its overexpression was negatively associated with the TNM stage (III + IV) (OR =0.41, 95% CI, 0.21-0.82, P=0.073. The combined sensitivity and specificity of EpCAM overexpression in the diagnosis of lung cancer were 0.79 (95% CI, 0.59-0.90) and 0.98 (95% CI, 0.95-0.99), respectively, and the SROC-AUC was 0.98 (95% CI, 0.97-0.99). Multivariate analysis of 322 lung cancer patients showed that there was no significant correlation between the EpCAM overexpression and prognosis of lung cancer (HR =2.28, 95% CI, 0.80-6.51, P=0.002). Deeks' funnel plot analysis showed the existence of publication bias (P=0.000). CONCLUSIONS: Our present findings suggested that EpCAM overexpression was not sensitive enough to predict the prognosis of lung cancer. Moreover, it was also a potential diagnostic indicator for lung cancer and correlated with TNM staging of lung cancer.

Identification of an Anti-Integrin αvß6 Autoantibody in Patients With Ulcerative Colitis.

BACKGROUND AND AIMS: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. METHODS: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. RESULTS: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvß6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti-integrin αvß6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti-integrin αvß6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvß6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvß6-fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. CONCLUSIONS: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvß6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity.

Enrichment of circulating tumor cells using a centrifugal affinity plate system.

Circulating tumor cells (CTCs) are defined as cells that have detached from a primary tumor and are circulating in the bloodstream. Their isolation and quantification is of great value for cancer prognoses and drug testing. Here, the development of a centrifugal affinity plate (CAP) system is described, in which centrifugal force and antibody-based capture are exploited to enrich CTCs on one plate and hematological cells on the other. The CAP is rotated to exert centrifugal force on the cells in a blood sample, quickly transporting them to the anti-epithelial adhesion molecule (EpCAM)-coated and anti-CD45-coated surface of the CAP to shorten the reaction time and increase the adhesion force between the tumor and blood cells and each antibody. The effect of a rotating process on cell capture was investigated, and the capture efficiency was demonstrated using blood samples from healthy donors spiked with human non-small cell lung cancer (NCI-H1650) and breast cancer (MCF-7) cells. The CAP system was capable of rapid isolation and identification of CTCs without the requirement for pretreatment of blood samples. Finally, the CAP system was tested to evaluate the detection efficiency of CTCs in the blood samples of breast cancer patients. The number of captured CTCs in only 1ml of blood varied from 6 to 10.