MicroRNA-155 inversely correlates with esophageal cancer progression through regulating tumor-associated macrophage FGF2 expression.

Esophageal cancer (EC) is one of the most common malignancies with high incidence and mortality. Tumor-associated macrophages (TAMs) in the tumor microenvironment have been linked to the accelerated tumor progression. MicroRNAs (miR) are 19-25 nucleotide-long, noncoding RNA molecules, functioning as modulators of gene expression, and mediate a variety of biological functions, including tumor growth. In the present study, the effects and molecular mechanism of miR-155 in TAMs isolated from EC were explored. The expression of miR-155 and fibroblast growth factor-2 (FGF2) in EC tissues and cell lines were analyzed using reverse transcription-quantitative PCR (qRT-PCR) and western blot assays. TAMs were also transfected with the described constructs. Following, the culture medium from TAMs was collected for further analysis. The released FGF2, and inflammatory cytokines were quantified using ELISA. The cell viability, migrated and invaded levels were calculated through Cell Counting kit-8 (CCK8), and transwell analysis. Moreover, human umbilical vein endothelial cells (HUVEC) vasculature formation was determined using matrigel angiogenesis analysis. The results indicated that miR-155 expression was decreased in EC tissues and cell lines, while FGF2 expression was increased in comparison to those in the normal control group. Moreover, miR-155 mimics transfection up-regulated tumor necrosis factor α (TNF-α), interleukin (IL)-12 and inducible nitric oxide synthase (iNOS), while down-regulated IL-10, Arginase-1 (Arg-1) and IL-22 levels in the culture medium from TAMs. And enhancing miR-155 expression in TAMs suppressed the cell viability, migration and invasion of ECA109 cells and reduced the angiogenesis. Nevertheless, over-expressing FGF2 abolished the role of miR-155 in cancer cell survival, migration, invasion as well as angiogenesis. Our findings indicated that miR-155-regulated FGF2 expression from TAMs suppressed EC cell proliferation, migration, invasion and inhibited vasculature formation. Thus, miR-155-modulated FGF2 might be a potential therapeutic target to prevent EC progression.

A panel of autoantibodies against multiple tumor-associated antigens in the immunodiagnosis of esophageal squamous cell cancer.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China with very low 5-year survival rate mostly due to the paucity of effective early diagnostic methods. Serum autoantibodies against 9 tumor-associated antigens (TAAs) from ESCC patients and healthy controls were detected by enzyme-linked immunosorbent assay to evaluate their performances in the immunodiagnosis of ESCC. Logistic regression models were generated to predict the probability of individuals being diagnosed with ESCC in training cohort (648 participants) and further validated in another independent cohort (372 participants). Finally, a panel of four TAAs showed high diagnostic accuracy with areas under the receiver operating characteristic curve of 0.838 in training cohort and 0.872 in validation cohort, respectively. The percentages of individuals correctly classified were 77.01 % in training cohort and 78.49 % in validation cohort, respectively. This model could discriminate early-stage (AJCC stage 0, I and II) ESCC patients from normal controls, with true-positive rate (TPR) of 67.57 % in training cohort and TPR of 63.33 % in validation cohort, and the overall TPR for early-stage ESCC was 66.85 % when the two cohorts were combined. The diagnostic performance of this model showed no significant difference between early-stage and late-stage (AJCC stage III and IV) ESCC patients. In summary, the optimized model with 4 TAAs has a high diagnostic performance for ESCC detection, especially for early-stage ESCC.

Tumor associated antigens or anti-TAA autoantibodies as biomarkers in the diagnosis of ovarian cancer: a systematic review with meta-analysis.

OBJECTIVE: This systematic review aims to outline and summarize known tumor-associated antigens (TAAs) or anti-TAA autoantibodies and their diagnostic values in ovarian cancer (OC). METHODS: A systematic literature search was conducted in two databases. Data were independently extracted and reviewed by two junior investigators and the disagreement was further resolved by consulting one of the senior investigators. RESULTS: Sixty publications reporting 113 different TAAs or anti-TAA autoantibodies were included. The majority of the studies were conducted in western countries. CA125, p53 and HE4 were the most frequently tested TAAs in OC. Meta-analysis showed that there was a significant association between serum anti-p53 autoantibody and increased risk of OC. CONCLUSION: Serum TAAs or anti-TAA autoantibodies are promising diagnostic biomarkers in the detection of OC. A customized mini-array of multiple TAAs may enhance the detection of anti-TAA autoantibodies in OC. Additional studies with sufficient number of OC patients and carefully selected controls are needed to further verify the results.

Mini-array of multiple tumor-associated antigens (TAAs) in the immunodiagnosis of esophageal cancer.

Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.