Impact of Socioeconomic Factors on Prognosis and Clinical Management in Patients with Hepatocellular Carcinoma.

BACKGROUND: The prognosis for patient survival using the tumor-node-metastasis (TNM) staging system may be imperfect, as it based only on biological factors and does not include the socioeconomic factors (SEFs). We integrated the SEFs into the TNM system (TNMSEF), and evaluated whether the novel TNM-SEF staging system showed better prediction capacity and improved clinical guidance in hepatocellular carcinoma (HCC). METHODS: We selected data of 12 514 cases with HCC between 2010 and 2015 from the SEER database. The Kaplan-Meier survival curves and Cox proportional hazards regression were used to analyze cancer-specific survival (CSS) among the TNM-SEF stages. RESULTS: Multivariate Cox analyses showed that insurance status, marital status, year of diagnosis, and income were prominent prognostic SEFs (all P < .05). When compared with the SEF0 stage, the SEF1 stage was significantly associated with a 36.1% increased risk of cancer-specific mortality in HCC overall, a 22.2% increased risk of metastatic HCC, and a 41.8% increased risk of non-metastatic HCC (all P < .001). The concordance index of the TNM-SEF stage (0.768) was better than that of the TNM stage (0.764). Furthermore, patients with SEF0 stage showed higher 5-year CSS than those with SEF1 stage (I: 48.7% vs. 28.1%; II: 41.0% vs. 25.1%; IIIA: 12.8% vs. 5.0%; IIIB: 7.8% vs. 6.0%; IIIC: 6.4% vs. 6.7%; IVA: 8.4% vs. 2.5%; IVB: 2.1% vs. 0.8%; all P < .05). CONCLUSION: We have proved that the SEF stage is an independent predictor for HCC. The combined SEF stage with TNM staging warrants more clinical attention, for improved prognostic prediction and clinical guidance.

Transcriptomic Landscape of von Economo Neurons in Human Anterior Cingulate Cortex Revealed by Microdissected-Cell RNA Sequencing.

The von Economo neurons (VENs) are specialized large bipolar projection neurons with restricted distribution in the human brain, and they are far more abundant in humans than in non-human primates. However, VEN functions remain elusive due to the difficulty of isolating VENs and dissecting their connections in the brain. Here, we combined laser-capture-microdissection with RNA sequencing to describe the transcriptomic profile of VENs from human anterior cingulate cortex (ACC). Using pyramidal neurons as reference cells, we identified 344 genes with VEN-associated expression differences, including 215 higher and 129 lower expression genes. Functional enrichment and protein-protein interaction network analyses showed that these genes with VEN-associated expression differences are involved in VEN morphogenesis and functions, such as dendrite branching and axon myelination, and many of them are associated with human social-emotional disorders. With the use of in situ hybridization and immunohistochemistry assays, we validated four novel VEN markers (VAT1L, CHST8, LYPD1, and SULF2). Collectively, we generated a full-spectrum expression profile of VENs from human ACC, greatly enlarging the pool of genes with VEN-associated expression differences that can help researchers to understand the role of VENs in normal and disordered human brains.

Quantitative assessment of AKAP12 promoter methylation in colorectal cancer using methylation-sensitive high resolution melting: Correlation with Duke's stage.

BACKGROUND: The expression of AKAP12 (A Kinase anchoring protein 12) is markedly reduced in a variety of cancers. The purpose of this study was to establish a methylation-sensitive high resolution melting (MS-HRM) assay for the quantitative detection of AKAP12 promoter methylation and expression and the association with clinicopathological variables in human colorectal cancer. We also assessed the effect of AKAP12 re-expression on cell growth and colony formation. RESULTS: Downregulation or loss of AKAP12 mRNA expression was detected in 31 of 45 tissue samples (68.9%). No significant correlation was observed between the reduced expression levels and patient age, gender, Duke's stage or tumor differentiation. Methylation (>1%) of the AKAP12 promoter region was present in 35 of 45 (77.8%) carcinoma tissue samples and 6 of 45 (13.3%) adjacent tissue samples. AKAP12 methylation was significantly higher in the colorectal cancer tissues exhibiting advanced Duke's stages. Treatment of the three colorectal carcinoma cell lines (LoVo, COLO320 and SW480) with completely methylated AKAP12 with inhibitors of DNA methyltransferase (5-Aza-2'-deoxycytidine) markedly increased expression of AKAP12 and decreased methylation levels. Ectopic expression of AKAP12 in the LoVo cell line suppressed cell growth and inhibited colony formation. METHODS: The AKAP12 gene was examined by quantitative RT-PCR, MS-HRM analysis and bisulfite sequencing in 45 paired tissue samples obtained from primary colorectal carcinomas and the corresponding adjacent tissues. In addition, five colorectal carcinoma cell lines (LoVo, COLO205, SW480, LS174T and COLO320) were investigated and western blot analysis was used to investigate changes in protein expression. A proliferation assay and soft agar assay were performed after overexpression of AKAP12. CONCLUSION: Our study demonstrated that MS-HRM is a robust, fast and sensitive method for AKAP12 methylation analysis. AKAP12 methylation represents a potential molecular biomarker for predicting the malignancy of this cancer.