BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers in the world,and the identification of biomarkers for the early detection is a relevant target. The purpose of the study is to discover specific low molecular weight (LMW) serum peptidome biomarkers and establish a diagnostic pattern for HCC.MethodsWe undertook this pilot study using a combined application of magnetic beads with Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique and ClinPro Tools v2.2 to detect 32 patients with HCC, 16 patients with chronic hepatitis (CH), 16 patients with liver cirrhosis (LC) and 16 healthy volunteers.ResultsThe results showed 49, 33 and 37 differential peptide peaks respectively appeared in HCC, LC and CH groups. A Supervised Neural Network (SNN) algorithm was used to set up the classification model. Eleven of the identified peaks at m/z 5247.62, 7637.05, 1450.87, 4054.21, 1073.37, 3883.64, 5064.37, 4644.96, 5805.51, 1866.47 and 6579.6 were used to construct the peptides patterns. According to the model, we could clearly distinguish between HCC patients and healthy controls as well as between LC or CH patients and healthy controls.ConclusionsThe study demonstrated that a combined application of magnetic beads with MALDI-TOF MB technique was suitable for identification of potential serum biomarkers for HCC and it is a promising way to establish a diagnostic pattern.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1503629821958720.

Metabolic reprogramming refers to the transformation of the whole metabolic network including glycolysis and mitochondrial metabolism, mainly manifested in Warburg effect and mitochondrial metabolic reprogramming. The roles of miR-145 in glycolysis have been established in ovarian cancer cells. Howerer, its roles in mitochondrial metabolic reprogramming are still unclear. This study aims to identify whether miR-145 regulates mitochondrial metabolic reprogramming in ovarian cancer cells. First, functional experiment showed that overexpression of miR-145 inhibited mitochondrial function in ovarian cancer cells, evident by the decreased mtDNA copy numbers, ATP level, mitochondrial membrane potential, and the expression levels of mitochondrial markers. Mechanistically, miR-145 inhibited mitochondrial function by targeting ARL5B directly. Futhermore, miR-145 overexpression decreased ARL5B expression in ovarian cancer tissue subcutaneous tumors of nude mice. In conclusion, we have highlighted that miR-145 inhibits mitochondrial function and achieves this by targeting ARL5B directly for the first time. The results provides a more adequate theoretical basis for understanding the molecular pathology of ovarian cancer, and provides the necessary basic data for miR-145 as a potential diagnosis and treatment target for ovarian cancer.

Background: Metaplastic breast cancer (MBC) is a rare subtype of breast cancer, and generally associated with poor outcomes. Lymph nodes metastasis (LNM) is confirmed as a critical independent prognostic factor and determine the optimal treatment strategies in MBC patients. We aimed to develop and validate a nomogram to predict the possibility of preoperative regional LNM in MBC patients.Methods: MBC patients diagnosed between 1990 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were included and stochastically divided into a training set and validation set at a ratio of 7:3. The risk variables of regional LNM in the training set were determined by univariate and multivariate logistic regression analyses. And then we integrated those risk factors to construct the nomogram. The prediction nomogram was further verified in the verification set. The discrimination, calibration and clinical utility of the nomogram were evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), calibration plots and decision curve analysis (DCA), respectively.Results: A total of 2205 female MBC patients were included in the study. Among the 2205 patients, 24.8% (546/2205) had positive regional lymph nodes. The nomogram for predicting the risk of regional LNM contained predictors of grade, estrogen receptor (ER) status and tumor size, with AUC of 0.683 (95% confidence interval (CI): 0.653-0.713) and 0.667 (95% CI: 0.621-0.712) in the training and validation sets, respectively. Calibration plots showed perfect agreement between actual and predicted regional LNM risks. At the same time, DCA of the nomogram demonstrated good clinical utilities.Conclusions: The nomogram established in this study showed excellent prediction ability, and could be used to preoperatively estimate the regional LNM risk in MBC.

Front Cover: The cover image is based on the ORIGINAL RESEARCH ARTICLE miR‐145 promotes miR‐133b expression through c‐myc and DNMT3A‐mediated methylation in ovarian cancer cells by Jie Li et al., https://doi.org/10.1002/jcp.29306. Cover Credit: Cover image © Jie li Images.

Objectives: To compare the effectiveness between Qi brush and Cervex-Brush ® Combi for the diagnosis of cervical lesions. Methods: After we registered a random-control clinical trial on the Chinese Clinical Trial Registry (No. XJTU1AF2017LSK-25), cervical cell samples were successively collected with both Qi brush and Cervex-Brush ® Combi before undergoing colposcope. Colposcopy with biopsy was performed later. Histological diagnosis was regarded as the gold standard in this study. The following indices of the two brushes were compared: sampling degree of satisfaction and presence rate of metaplastic cells, together with sensitivity (Se), specificity (Sp), false positives (FP), false negatives (FN), positive predictive value (PPV), and negative predictive value (NPV). The kappa value was used to measure the inter-rater agreement of the Qi brush and Cervex-Brush ® Combi in diagnosing cervical lesions. Results: In total, 74 patients were enrolled in this study. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Qi brush were 57.14, 86.84, 76.19, and 73.33%, respectively. For the Cervex-Brush ® Combi, they were 26.92, 88.89, 63.63, and 62.75%, respectively. In addition, the Qi brush had a higher satisfied sampling rate (89.19%) than the Cervex-Brush ® Combi (83.78%), and the P-value was 0.336 using Chi-square test. The kappa value was 0.444, which indicated a medium agreement between these two brushes, and the sensitivity of the Qi brush was higher than that of the Cervex-Brush ® Combi, with significant statistical difference (P = 0.039<0.05). Conclusions: The Qi brush was more effective than the Cervex-Brush ® Combi for sampling and also had a slightly higher accuracy in diagnosing in cytology. In terms of social and economic benefits, the Qi brush may be a better cervical cytology collector.

RNA methylation can reverse the methylation modification at RNA level, which is a kind of extremely important epigenetic modification. YTHDF2, as a reader of m6A modification, the function and mechanisms of in epithelial ovarian cancer(EOC) have not been elucidated so far. In this study, we demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues, further function studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines, and reduced the global mRNA m6A levels. Next, we found that the expression levels of miR-145 and YTHDF2 were inversely correlated in ovarian cancer tissues and cells, and YTHDF2 is the direct target gene of miR-145. Interestingly, there was a crucial crosstalk between miR-145 and YTHDF2 via a double-negative feedback loop. Overexpression of YTHDF2 rescues miR-145-induced reduction of proliferation and migration in EOC cells. To conclude, YTHDF2 and miR-145, as two crucial m6A regulators, are involved in the progression of EOC by indirectly modulating m6A levels. In view of these promising results, YTHDF2 and miR-145 may provide new insights into the carcinogenesis and new potential therapeutic targets for EOC.

RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC.