Biomarkers for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The HCC diagnosis is usually achieved by biomarkers, which can also help in prognosis prediction. Furthermore, it might represent certain therapeutic interventions through some combinations of biomarkers. Here, we review on our current understanding of HCC biomarkers

IQGAP1 Mediates Hcp1-Promoted Escherichia coli Meningitis by Stimulating the MAPK Pathway

Escherichia coli-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1. IQGAP1 was found to be up-regulated by Hcp1 treatment and mediate the stimulation of HBMEC apoptosis. It was shown that Hcp1 could compete against Smurf1 for binding to IQGAP1, thereby rescuing the latter from ubiquitin-dependent degradation. Subsequent study suggested that IQGAP1 could stimulate the MAPK signaling pathway by promoting the phosphorylation of ERK1/2, an effect that was blocked by U0126, an MAPK inhibitor. Furthermore, U0126 also demonstrated therapeutic potential against E. coli meningitis in a mouse model. Taken together, our results suggested the feasibility of targeting the MAPK pathway as a putative therapeutic strategy against bacterial meningitis

Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing

Abstract Liquid biopsy by genotyping circulating tumor DNA (ctDNA) has provided a non-invasive approach in assessing tumor genomic alterations in clinical oncology. However, emerging evidence in clinical settings has shown significant discordance in the genomic alterations between matched tumor tissue and blood ctDNA samples, and even between the same set of blood samples analyzed on different testing platforms. Thus, it is necessary to study underlying causes of discrepancies in these studies by genotyping tumor tissue and ctDNA in parallel using next generation sequencing (NGS) panels based on the same technology. Here we enrolled 56 non-small-cell lung cancer (NSCLC) patients and evaluated tumor tissue genotyping and ctDNA based liquid biopsy by parallel NGS panel testing and compared different sample preparation conditions. Somatic mutations in plasma cell-free DNA (cfDNA) were detected in 63.6% patients with early-stage NSCLC and 60% patients with advanced-stage NSCLC. The overall concordance between matched formalin-fixed paraffin-embedded sample and cfDNA was 54.6% in early-stage NSCLC patients and 80% in advanced-stage NSCLC patients. The positive concordance rate was 44.4% and 71.4% in early-stage and advanced-stage patients, respectively. Using fresh frozen tumor samples did not improve the overall concordance rate between matched tumor tissue and cfDNA. Processing blood samples beyond 4 h after blood draw significantly decreased the detection rate of somatic mutations in cfDNA. Thus, the concordance rate between tumor tissue-based and ctDNA-based genotyping in clinical samples can be affected by multiple pre-analytical, analytical and biologic factors. Parallel NGS panel testing on both sample types for each patient may be warranted for effective guidance of cancer targeted therapies and possible early detection of cancer

More effective strategies are required to strengthen public awareness of COVID-19: evidence from Google Trends

Background: The outbreak of coronavirus disease 2019 (COVID-19) has posed stress on the health and well-being of both Chinese people and the public worldwide. Global public interest in this new issue largely reflects people's attention to COVID-19 and their willingness to take precautionary actions. This study aimed to examine global public awareness of COVID-19 using Google Trends. Methods: Using Google Trends, we retrieved public query data for terms of "2019-nCoV + SARS-CoV-2 + novel coronavirus + new coronavirus + COVID-19 + Corona Virus Disease 2019" between the 31st December 2019 and the 24th February 2020 in six major English-speaking countries, including the USA, the UK, Canada, Ireland, Australia, and New Zealand. Dynamic series analysis demonstrates the overall change trend of relative search volume (RSV) for the topic on COVID-19. We compared the top-ranking related queries and sub-regions distribution of RSV about COVID-19 across different countries. The correlation between daily search volumes on the topic related to COVID-19 and the daily number of people infected with SARS-CoV-2 was analyzed. Results: The overall search trend of RSV regarding COVID-19 increased during the early period of observing time and reached the first apex on 31st January 2020. A shorter response time and a longer duration of public attention to COVID-19 was observed in public from the USA, the UK, Australia, and Canada, than that in Ireland and New Zealand. A slightly positive correlation between daily RSV about COVID-19 and the daily number of confirmed cases was observed (P

Quantification of Rare Circulating Tumor Cells in Non-Small Cell Lung Cancer by Ligand-Targeted PCR

<div><p>Background</p><p>Quantification of circulating tumor cells (CTC) is valuable for evaluation of non-small cell lung cancer (NSCLC). The sensitivity of current methods constrains their use to detect rare CTCs in early stage. Here we evaluate a novel method, ligand-targeted polymerase chain reaction (LT-PCR), that can detect rare CTCs in NSCLC patients.</p><p>Methods</p><p>CTCs were enriched by immunomagnetic depletion of leukocytes and then labeled by a conjugate of a tumor-specific ligand and an oligonucleotide. After washing off free conjugates, the bound conjugates were stripped from CTCs and then analyzed by qPCR. To evaluate the clinical utility, blood samples were obtained from 72 NSCLC patients (33 initially diagnosed and 39 on chemotherapy), 20 benign patients, and 24 healthy donors.</p><p>Results</p><p>Experiments with healthy blood spiked with tumor cells indicated the LT-PCR allows specific detection of CTC. The clinical study showed that the initially diagnosed patients have an average of 20.8 CTC units with metastatic diseases, 11.8 CTC units with localized diseases, and 6.0 CTC units with benign diseases. With the threshold of 8.5 CTC units, the assay can detect 80% of stage I/II, 67% of stage III, and 93% of stage IV cancer. With the benign patients and healthy donors as control group, the method can detect cancer with a sensitivity of 81.8% and a specificity of 93.2%.</p><p>Conclusion</p><p>The LT-PCR would allow quantification of CTC in NSCLC patients at a more sensitive level, providing a potential tool for stratifying malignant lung diseases, especially at early stage.</p></div

CTC prevalence in initially diagnosed patients.

<p>A) CTC levels in localized and metastatic malignant lung disease, benign lung disease and healthy donors. B) Distribution of CTC levels in different histological subtypes. ADC, adenocarcinoma; SCC, squamous cell carcinoma. C) Receiver operating characteristic (ROC) analysis between malignant lung disease group and benign disease and healthy group.</p

Immunostaining of the cultured KB cells and enriched CTCs.

<p>KB cells (A–D) and enriched CTCs from two metastatic NSCLC patients (CTC sample1: E–H; CTC sample 2: I–L) were fixed by methanol, and stained for cytokeratin (A,E and I) and folate receptor (FR) (B, F and J). The cell nucleus was labeled by DAPI (C, G and K). The merged images showed cytokeratin and folate receptor are expressed only in CTCs (H and L) and KB cells (D), not in haematologic cells.</p

Correlation of CTC levels between NSCLC patients and chemotherapy treatment.

<p><i>w/o chemo</i>, initially diagnosed NSCLC patients; <i>with chemo</i>, NSCLC patients on chemotherapy.</p