OSchol: an online consensus survival web server for cholangiocarcinoma prognosis analysis.

BACKGROUND: As the most common biliary ducts, cholangiocarcinoma (CHOL) is an aggressive malignancy with complex pathological context, high mortality and relapse rate. The current therapy of CHOL is mainly performed with surgery followed by chemoradiotherapy. Due to the high metastasis and relapse rate of CHOL, the prognosis of CHOL is still poor, and the molecular prognostic system is to be constructed. METHODS: In this study, we have established an online prognostic analysis web server named OSchol to evaluate the correlation between candidate genes and survival for CHOL. RESULTS: The prognostic values of previous published biomarkers in OSchol, including ITIH4, PTEN and DACH1, have been validated by OSchol. In addition, we have identified novel potential prognostic biomarker for CHOL using OSchol, that E2F1 has significant prognostic ability in OSchol (both TCGA and GSE107943 cohorts). CONCLUSION: Our study provides a platform for researchers and clinicians to screen, develop and validate their genes of interest to be potential prognostic biomarkers for CHOL and may also help guide the targeted therapies for CHOL.

Interactive online consensus survival tool for esophageal squamous cell carcinoma prognosis analysis.

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer worldwide. However, operative diagnostic and prognostic systems for ESCC remain to be established. To improve assessment of the prognosis for patients with ESCC, the present study developed an online consensus survival tool for ESCC, termed OSescc. OSescc was built using 264 ESCC cases with gene expression data and relevant clinical information obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Kaplan-Meier survival plots with hazard ratios and P-values were generated by OSescc to predict the association between potential biomarkers and relapse free survival and overall survival. In addition, the current study integrated a function by which one could assess the prognosis based on an individual probe or the mean value of multiple probes for each gene, which helped improve the evaluation of the validity and reliability of the potential prognosis biomarkers. OSescc can be accessed at bioinfo.henu.edu.cn/DBList.jsp.

Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, particularly in Asian populations, and responds poorly to conventional therapy. Subclassification of ESCCs by molecular analysis is a powerful strategy in extending conventional clinicopathologic classification, improving prognosis and therapy. Here we identified two ESCC molecular subtypes in Chinese population using gene expression profiling data and further validated the molecular subtypes in two other independent Asian populations (Japanese and Vietnamese). Subtype I ESCCs were enriched in pathways including immune response, while genes overexpressed in subtype II ESCCs were mainly involved in ectoderm development, glycolysis process, and cell proliferation. Specifically, we identified potential ESCC subtype-specific diagnostic markers (FOXA1 and EYA2 for subtype I, LAMC2 and KRT14 for subtype II) and further validated them in a fourth Asian cohort. In addition, we propose a few subtype-specific therapeutic targets for ESCC, which may guide future ESCC clinical treatment when further validated.

High Sensitive and Non-invasive ctDNAs Sequencing Facilitate Clinical Diagnosis And Clinical Guidance of Non-small Cell Lung Cancer Patient: A Time Course Study.

Lung cancer is one of leading causes of cancer death all over the world. Non-small cell lung cancer (NSCLC) is the most predominant subtype of lung cancer. Molecular targeting therapy has been shown great success in the treatment of advanced NSCLC. Thus, an easy, sensitive, and specific way of recognizing therapeutic gene targets would help to select effective treatments, to improve physical condition and increase patient survival. In this study, we recruited and followed up a female NSCLC patient, whose plasma ctDNAs (circulating tumor DNAs), blood cell DNAs, psDNAs (pleural effusion supernatant DNAs), and ppDNAs (pleural effusion pellet DNAs), were collected and analyzed over periodic time points by methods of next generation sequencing (NGS), droplet digital PCR (ddPCR), and Amplification Refractory Mutation System (ARMS). In addition, pleural effusion pellets were stained by IHC (immunohistochemistry). The investigation results showed that EGFR L858R mutation was recognized by methods of NGS, ddPCR, and ARMS, while EGFR T790M mutation was only identified by methods of NGS and ddPCR but not ARMS, indicating that ARMS as an auxiliary clinical diagnostic method, is less sensitive and less reliable than NGS and ddPCR. In summary, the non-invasive and sensitive way of collecting ctDNAs for NGS and/or ddPCR screenings offers patients new diagnosis and therapeutic options.

A chimeric protein PTEN-L-p53 enters U251 cells to repress proliferation and invasion.

PTEN, a well-known tumor suppressor, dephosphorylates PIP3 and inhibits AKT activity. A translational variant of PTEN has been identified and termed PTEN-Long (PTEN-L). The additional 173 amino acids (PTEN-L leader) at the N-terminal constitute a potential signal peptide. Differing from canonical PTEN, PTEN-L is secreted into the extracellular fluid and re-enters recipient cells, playing the similar roles as PTEN in vivo and in vitro. This character confers the PTEN-L a therapeutic ability via directly protein delivering instead of traditional DNA and RNA vector options. In the present study, we employed PTEN-L leader to assemble a fusion protein, PTEN-L-p53, inosculated with the transcriptional regulator TP53, which is another powerful tumor suppressor. We overexpressed PTEN-L-p53 in HEK293T cells and detected it in both the cytoplasm and nucleus. Subsequently, we found that PTEN-L-p53 was secreted outside of the cells and detected in the culture media by immunoblotting. Furthermore, we demonstrated that PTEN-L-p53 freely entered the cells and suppressed the viability of U251cells (p53R273H, a cell line with p53 R273H-mutation). PTEN-L-p53 is composed of endogenous protein/peptide bearing low immunogenicity, and only the junction region between PTEN-L leader and p53 can act as a new immune epitope. Accordingly, this fusion protein can potentially be used as a therapeutic option for TP53-abnormality cancers.