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Microvascular invasion (MVI) is an adverse factor for the prognosis of patients with hepatocellular carcinoma (HCC). We aimed to construct a preoperative prediction model for MVI, thereby providing a reference for clinicians in formulating treatment options for HCC. A total of 360 patients with non-metastatic HCC were retrospectively enrolled. We used logistic regression analysis to screen out independent risk factors for MVI and further constructed a predictive model for MVI. The performance of the model was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Logistic regression analysis revealed that fibrinogen (>4 g/L) (OR: 6.529), alpha-fetoprotein (≥ 400 ng/mL) (OR: 2.676), cirrhosis (OR: 2.25), tumor size (OR: 1.239), and poor tumor border (OR: 3.126) were independent risk factors of MVI. The prediction model of MVI had C-index of 0.746 and 0.772 in the training and validation cohorts, respectively. The calibration curves showed good agreement between actual and predicted MVI risk. Finally, DCA reveals that this model has good clinical utility. The nomogram-based model we established can predict the preoperative MVI well and provides reference for surgeons to make clinical treatment decisions. [ABSTRACT FROM AUTHOR]

Objectives: Sjögren's syndrome (SS), a systemic autoimmune disorder, is characterized by dry mouth and eyes. However, SS pathogenesis is poorly understood. We performed bioinformatics analysis to investigate the potential targets and molecular pathogenesis of SS. Methods: Gene expression profiles (GSE157159) and methylation data (GSE110007) associated with SS patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially methylated positions (DMPs) and differentially expressed genes (DEGs) were identified by the R package limma. The potential biological functions of DEGs were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Key DMPs were selected by overlap and the shrunken centroid algorithm, and corresponding genes were identified as hub genes, with their diagnostic value assessed by receiver operating characteristic (ROC) curves. The potential molecular mechanisms of hub genes were analyzed by protein–protein interaction (PPI) networks and single-gene gene set enrichment analysis (GSEA). Peripheral blood mononuclear cells (PBMCs) were collected from control and SS patients at The Affiliated Hospital of Southwest Medical University and Dazhou Central Hospital. The mRNA levels of hub genes were verified by quantitative real-time polymerase chain reaction (qRT–PCR). Results: We identified 788 DMPs and 2457 DEGs between the two groups. Functional enrichment analysis suggested that the DEGs were significantly enriched in T cell activation, leukocyte cell–cell adhesion, and cytokine–cytokine receptor interaction. TSS200, TSS1500, and 1stExon were identified as highly enriched areas of differentially methylated promoter CpG islands (DMCIs). In total, 61 differentially methylated genes (DMGs) were identified by the overlap of 2457 DEGs and 507 genes related to DMPs (DMPGs), of which 21 genes located near TSS200, TSS1500, and 1stExon were selected. Then, three key DMPs and the corresponding hub genes (RUNX3, HLA-DPA1, and CD6) were screened by the shrunken centroid algorithm and calculated to have areas under the ROC curve of 1.000, 0.931, and 0.986, respectively, indicating good diagnostic value. The GSEA results suggested that all three hub genes were highly associated with the immune response. Finally, positive mRNA expression of the three hub genes in clinical SS samples was verified by qRT–PCR, consistent with the GSE157159 data. Conclusions: The identification of three hub genes provides novel insight into molecular mechanisms and therapeutic targets for SS. Key Points • Hub genes were screened by DNA methylation and transcriptome analyses. • The relative expression of hub genes in peripheral blood samples was verified by qRT–PCR. • HLA-DPA1 was correlated with the pathogenic mechanism of SS. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. Methods: Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. Results: Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. Conclusions: We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether incorporating the radiomics, genomics, and clinical features allows prediction of metastasis in colorectal cancer (CRC) and to develop a preoperative nomogram for predicting metastasis. Methods: We retrospectively analyzed radiomics features of computed tomography (CT) images in 134 patients (62 in the primary cohort, 28 in the validation cohort, and 44 in the independent-test cohort) clinicopathologically diagnosed with CRC at Dazhou Central Hospital from February 2018 to October 2019. Tumor tissues were collected from all patients for RNA sequencing, and clinical data were obtained from medical records. A total of 854 radiomics features were extracted from enhanced venous-phase CT of CRC. Least absolute shrinkage and selection operator regression analysis was utilized for data dimension reduction, feature screen, and radiomics signature development. Multivariable logistic regression analysis was performed to build a multiscale predicting model incorporating the radiomics, genomics, and clinical features. The receiver operating characteristic curve, calibration curve, and decision curve were conducted to evaluate the performance of the nomogram. Results: The radiomics signature based on 16 selected radiomics features showed good performance in metastasis assessment in both primary [area under the curve (AUC) = 0.945, 95% confidence interval (CI) 0.892–0.998] and validation cohorts (AUC = 0.754, 95% CI 0.570–0.938). The multiscale nomogram model contained radiomics features signatures, four-gene expression related to cell cycle pathway, and CA 19-9 level. The multiscale model showed good discrimination performance in the primary cohort (AUC = 0.981, 95% CI 0.953–1.000), the validation cohort (AUC = 0.822, 95% CI 0.635–1.000), and the independent-test cohort (AUC = 0.752, 95% CI 0.608–0.896) and good calibration. Decision curve analysis confirmed the clinical application value of the multiscale model. Conclusion: This study presented a multiscale model that incorporated the radiological eigenvalues, genomics features, and CA 19-9, which could be conveniently utilized to facilitate the individualized preoperatively assessing metastasis in CRC patients. [ABSTRACT FROM AUTHOR]

Introduction: Worldwide, the incidence and mortality of lung cancer are at the highest levels, and the most lesions are located in the lung periphery. Despite extensive screening and diagnosis, the pathologic types of peripheral pulmonary lesions (PPLs) are difficult to diagnose by noninvasive examination. This study aimed to identify a novel index—time difference of arrival (TDOA)—to discriminate between benign inflammation and malignant PPLs. Methods: Using contrast-enhanced ultrasound (CEUS), we retrospectively analyzed 96 patients with PPLs who had undergone biopsy to confirm the pathologic types. All data were collected from Dazhou Central Hospital between December 2012 and July 2019. The parameters of CEUS were analyzed by two assistant chief physicians of ultrasound diagnosis. Area under the receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the diagnostic ability of different indices. Results: We found that the TDOA significantly distinguished benign inflammation from malignant lesions. The TDOA was markedly increased in patients with malignant lesions than benign inflammation lesions (P < 0.001). Compared with conventional time-intensity curve (TIC) indices, TDOA showed high diagnostic accuracy (area under the curve = 0.894). Moreover, conventional diagnostic indices did not affect the diagnostic performance of TDOA by adjusting the receiver operating characteristic curve. Conclusion: TDOA is feasible for the diagnosis of benign inflammation and malignant PPLs. [ABSTRACT FROM AUTHOR]

• The deep learning radiomics model showed good performance in lymph node metastasis (LNM) prediction of colorectal cancer (CRC) patients. • The genes correlated to selected deep learning features mainly enriched in catabolic processes and immune-related pathways in CRC patients. • The genes in the immune pathways significantly decreased from non-LNM to LNM in CRC patients. The preoperative lymph node (LN) status is important for the treatment of colorectal cancer (CRC). Here, we established and validated a deep learning (DPL) model for predicting lymph node metastasis (LNM) in CRC. A total of 423 CRC patients were divided into cohort 1 (training set, n = 238, testing set, n = 101) and cohort 2 (validation set, n = 84). Among them, 84 patients' tumour tissues were collected for RNA sequencing. The DPL features were extracted from enhanced venous-phase computed tomography of CRC using an autoencoder. A DPL model was constructed with the least absolute shrinkage and selection operator algorithm. Carcinoembryonic antigen and carbohydrate antigen 19-9 were incorporated into the DPL model to construct a combined model. The model performance was assessed by receiver operating characteristic curves, calibration curves and decision curves. The correlations between DPL features, which have been selected, and genes were analysed by Spearman' correlation, and the genes correlated with DPL features were used to transcriptomic analysis. The DPL model, integrated with 20 DPL features, showed a good discrimination performance in predicting the LNM, with areas under the curves (AUCs) of 0.79, 0.73 and 0.70 in the training set, testing set and validation set, respectively. The combined model had a better performance, with AUCs of 0.81, 0.77 and 0.73 in the three sets, respectively. Decision curve analysis confirmed the clinical application value of the DPL model and combined model. Furthermore, catabolic processes and immune-related pathways were identified and related with the selected DPL features. This study presented a DPL model and a combined model for LNM prediction. We explored the potential genomic phenotypes related with DPL features. In addition, the model could potentially be utilized to facilitate the individualized prediction of LNM in CRC. [ABSTRACT FROM AUTHOR]