Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Metal-free electrochemistry promoted radical cascade cyclization to access CF3-containing benzimidazo[2,1-a]isoquinolin-6(5H)-ones.

Using CF3SO2Na as the CF3 radical source, an eco-friendly approach for electrochemistry-mediated radical cascade cyclization of N-methacryloyl-2-phenylbenzoimidazoles was described. This reaction features mild reaction conditions, readily available substrates, and moderate to good yields through the construction of two C-C bonds in one step.

Metal-free regioselective mono- and poly-halogenation of 2-substituted indazoles.

An unprecedented metal-free regioselective halogenation of 2H-indazoles has been revealed, which not only realized the highly selective synthesis of mono-halogenated products, but also completed poly-halogenations by fine tuning the reaction conditions. Various mono-/poly-/hetero-halogenated indazoles were obtained in moderate to excellent yields. Notably, this approach features environmentally friendly solvents, mild reaction conditions, simple execution and short reaction time.

HNRNPA2B1 Demonstrates Diagnostic and Prognostic Values Based on Pan-Cancer Analyses.

Some studies have suggested heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) to be a promoter in cancer development. Nonetheless, no detailed pan-cancer investigation has been reported. Thus, this study explored the possible oncogenic role of HNRNPA2B1, such as its expression levels, gene alteration, protein-protein interaction network, immune infiltration, and prognostic value in different cancer types using The Cancer Genome Atlas web platform. Many types of cancer exhibit HNRNPA2B1 overexpression, which is notably associated with poor prognosis. We also found that HNRNPA2B1 with different methylation levels causes a varied prognosis in lung adenocarcinoma (LUAD). It is noteworthy that HNRNPA2B1 levels are connected with cancer-associated fibroblasts in cancers, such as adrenocortical carcinoma, LUAD, and stomach adenocarcinoma. In addition, HNRNPA2B1 participates in the spliceosome- and cell cycle-associated pathways. Finally, HNRNPA2B1 is highly valued in the diagnosis of LUAD, lung squamous cell carcinoma, breast invasive carcinoma, esophageal carcinoma, and liver hepatocellular carcinoma. This systematic study highlighted the role of HNRNPA2B1 in pan-cancer progression.

The RNA N6 -methyladenosine modulator HNRNPA2B1 is involved in the development of non-small cell lung cancer.

The key N6  methyladenosine (m6 A) RNA methylation regulator is associated with multiple tumour progression. However, the m6 A-associated regulators that influence non-small cell lung cancer (NSCLC) development have not been fully clarified. The m6 A regulator expression pattern of NSCLC patients from The Cancer Genome Atlas (TCGA) dataset was identified. Aberrations of m6A modulators are related to NSCLC development via cBioPortal database. Furthermore, we found that IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO are significantly correlated with advanced stage disease or clinical outcomes in NSCLC by UALCAN and Kaplan-Meier plot. Bioinformatics analysis showed that m6 A modulators (IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO) are associated with immunomodulator and immune infiltration expression in NSCLC via the Tumor Immune Estimation Resource (TIMER) database. The co-expression between these m6A-associated modulators was analysed by protein-protein interaction networks. Finally, we found that HNRNPA2B1 promotes NSCLC development in vitro by regulating cell proliferation and metastasis functions via Cell Counting Kit 8 (CCK8) and transwell assay. Our study showed that HNRNPA2B1 is a promising target and biomarker for cancer therapy in NSCLC.

Study of the Effects of Air Pollutants on Human Health Based on Baidu Indices of Disease Symptoms and Air Quality Monitoring Data in Beijing, China.

There is an increasing body of evidence showing the impact of air pollutants on human health such as on the respiratory, and cardio- and cerebrovascular systems. In China, as people begin to pay more attention to air quality, recent research focused on the quantitative assessment of the effects of air pollutants on human health. To assess the health effects of air pollutants and to construct an indicator placing emphasis on health impact, a generalized additive model was selected to assess the health burden caused by air pollution. We obtained Baidu indices (an evaluation indicator launched by Baidu Corporation to reflect the search popularity of keywords from its search engine) to assess daily query frequencies of 25 keywords considered associated with air pollution-related diseases. Moreover, we also calculated the daily concentrations of major air pollutants (including PM10, PM2.5, SO2, O3, NO2, and CO) and the daily air quality index (AQI) values, and three meteorological factors: daily mean wind level, daily mean air temperature, and daily mean relative humidity. These data cover the area of Beijing from 1 March 2015 to 30 April 2017. Through the analysis, we produced the relative risks (RRs) of the six main air pollutants for respiratory, and cardio- and cerebrovascular diseases. The results showed that O3 and NO2 have the highest health impact, followed by PM10 and PM2.5. The effects of any pollutant on cardiovascular diseases was consistently higher than on respiratory diseases. Furthermore, we evaluated the currently used AQI in China and proposed an RR-based index (health AQI, HAQI) that is intended for better indicating the effects of air pollutants on respiratory, and cardio- and cerebrovascular diseases than AQI. A higher Pearson correlation coefficient between HAQI and RRTotal than that between AQI and RRTotal endorsed our efforts.