Lung cancer is the leading cause of cancer mortality worldwide. Although many biomarkers have been identified for lung cancer, their low specificity and sensitivity present an urgent need for the identification of more candidate biomarkers. In this study, we conducted MRM-based targeted analysis to evaluate the potential utility of a list of candidate proteins for lung cancer diagnosis. A total of 1249 transitions of 420 peptides representing 102 candidate proteins from our previous study and the literature were first screened by MRM analysis in pooled plasma samples, resulting in 78 proteins remaining in the list. Relative quantification of these 78 proteins was further performed in 60 individual plasma samples from lung adenocarcinoma patients in stages I-III and matched healthy control subjects. Ultimately, nine proteins were found to be able to distinguish patients from controls. Further combinations of five, three, and two candidate marker proteins improved the sensitivity to discriminate patients from controls and resulted in a merged AUC value of nearly 1.00 in stages I-III patients versus controls. Our results highlighted several possible markers for lung adenocarcinoma, and the proposed protein panels require further validation in a larger cohort to evaluate their potential use in clinical applications or development of therapeutics.

BackgroundFive RecQ helicase family members have a role in maintaining genome stability. However, their prognostic roles in breast cancer remain unknown. We aimed to investigate the prognostic values of the RecQ family and clinical outcomes in breast cancer.MethodsWe used the Kaplan–Meier Plotter database (http://kmplot.com/analysis) to analyze prognostic values of RecQ-family mRNA expression in all breast cancers and in different intrinsic subtypes and clinicopathological characteristics. Protein-expression levels of WRN and RECQL4 were confirmed by immunohistochemistry (IHC) in breast cancer tissues.ResultsIncreased expression of RECQL mRNA was significantly associated with reduced relapse-free survival (RFS) and postprogression survival (PPS) in all breast cancers, and improved overall survival (OS) in patients with basal-like breast cancer and in mutant-p53-type breast cancer patients. Increased expression of BLM mRNA was correlated with reduced distant metastasis-free survival (DMFS) in all patients. Increased expression of WRN mRNA was associated with improved OS and RFS in breast cancer patients. Increased expression of RECQL4 mRNA was associated with reduced OS, DMFS, and RFS in all breast cancers, and with reduced OS in patients with luminal A, HER2-positive, ER-positive, and PR-positive breast cancer. Increased expression of RECQL5 mRNA was associated with improved RFS in all patients, and with improved OS in patients with lymph-node-negative breast cancer, but with reduced OS in patients with HER2-positive breast cancer. IHC staining confirmed that high expression of WRN was correlated with increased OS and high expression of RECQL4 associated with reduced OS at protein levels.ConclusionmRNA-expression levels of RecQ members were significantly correlated with prognosis in breast cancer patients. These preliminary findings require further study to determine whether RecQ-targeting reagents might be developed for clinical application in breast cancer.

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Colorectal cancer is the most common form of cancer in the world, and the five-year survival rate is estimated to be almost 90% in the early stages. Therefore, the identification of potential biomarkers to assess the prognosis of early stage colorectal cancer patients is critical for further clinical treatment. Dysregulated tyrosine phosphorylation has been found in several diseases that play a significant regulator of signaling in cellular pathways. In this study, this strategy was used to characterize the tyrosine phosphoproteome of colorectal cell lines with different progression abilities (SW480 and SW620). We identified a total of 280 phosphotyrosine (pTyr) peptides comprising 287 pTyr sites from 261 proteins. Label-free quantitative analysis revealed the differential level of a total of 103 pTyr peptides between SW480 and SW620 cells. We showed that cyclin-dependent kinase I (CDK1) pTyr15 level in SW480 cells was 3.3-fold greater than in SW620 cells, and these data corresponded with the label-free mass spectrometry-based proteomic quantification analysis. High level CDK1 pTyr15 was associated with prolonged disease-free survival for stage II colorectal cancer patients (n = 79). Taken together, our results suggest that the CDK1 pTyr15 protein is a potential indicator of the progression of colorectal cancer.

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Dioscorea Bulbifera L. (DBL), an effective traditional Chinese medicine, has been restricted because of multiple reports that it can cause severe hepatotoxicity. 8-Epidiosbulbin E acetate (EEA), one of the main components of DBL, can induce severe liver injury. It has been reported that EEA can be metabolized by CYP3A to the corresponding cis-enedial intermediate which alkylates the lysine residues of proteins to form pyrroline derivatives. The present study unexpectedly found that the reactive intermediate reacted with the amide groups of asparagine (Asn) and glutamine (Gln) residues of hepatic proteins of mice treated with EEA. The amide-derived protein modification increased with the increase in the dose administered. Like the adduction of the primary amine of lysine residues, the electrophilic metabolite reacted with the amide groups of Asn and Gln residues to offer the corresponding pyrrolines. The structures of the pyrrolines were confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy.

The rational design of selective histone deacetylase 2 (HDAC2) inhibitors is beneficial for the therapeutic treatment of liver cancer, though HDAC2 is highly homologous to HDAC8, which may lead to...