Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy.

Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of this cancer type heterogeneity. LUAD subtypes were identified on the basis of the immunogenomic profiling of 29 immune signatures. We named three LUAD subtypes: Immunity High, Immunity Medium, and Immunity Low. The Immunity High subtype was characterized by immune activation, e.g., increased immune scores, elevated stromal scores and the highest infiltration of CD8+ T cells, and decreased tumor purities. Activated expressions of human leukocyte antigen (HLA) genes, immune checkpoint molecules, and T helper 1 (Th1)/interferon-gamma (IFNγ) gene signature were also observed in the Immunity High subtype. N 6-methyladenosine (m6A) RNA methylation, associated with cancer initiation and progression, was reduced in the Immunity High subtype. Functional and signaling pathway enrichment analysis further showed that differentially expressed genes between the Immunity High subtype and the other subtypes mainly participated in immune response and some cancer-associated pathways. In addition, the Immunity High subtype exhibited more sensitivity to immunotherapy and chemotherapy. Finally, candidate compounds that aimed at LUAD subtype differentiation were identified. Comprehensively characterizing the LUAD subtypes based on immune signatures may help to provide potential strategies for LUAD treatment.

Diagnostic Value of Autoantibodies against Ezrin in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC), one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (P < 0.0001). Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (P < 0.0001). Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC.

Tumor-associated autoantibodies against Fascin as a novel diagnostic biomarker for esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVE: Autoantibodies against tumor-associated antigens (TAAs) have been found in many kinds of cancers, and might serve as biomarkers for early cancer diagnosis. The present study was carried out to test if there is any relation between autoantibodies against Fascin and esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and forty-nine patients with ESCC and 98 control subjects were recruited in the study. The levels of circulating autoantibodies against Fascin were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) was used to calculate diagnostic accuracy. RESULT: The levels of autoantibodies against Fascin in patients with ESCC were significantly higher than in control subjects (P<0.001). Measurement of autoantibodies against Fascin provided an area under the curve (AUC) of 0.636, [95% confidence interval (CI): 0.568-0.704] 24.8% sensitivity (95% CI: 18.3%-37.2%) and 99.0% specificity (95% CI: 93.6%-99.9%). Moreover, serum level of autoantibodies against Fascin in early-stage ESCC was significantly higher than that of normal controls (P<0.05). The positive rates of autoantibodies against Fascin were correlated with age (P<0.05), but not with gender, tumor size, tumor site, histological grade, T stage, N stage or TNM stage (P>0.05). CONCLUSIONS: Our results suggest that Fascin autoantibody may be a potential biomarker for the early detection of ESCC.