Endovascular Embolization for Idiopathic Serial Right Internal Mammary Artery Aneurysms.

CLINICAL IMAPCT: This article showed images of a patient with idiopathic serial right internal mammary artery true aneurysms treated by endovascular embolization, which is a rare diagnosis and should be considered in differential diagnosis of paratracheal mass.

HCCDB v2.0: Decompose Expression Variations by Single-cell RNA-seq and Spatial Transcriptomics in HCC.

Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma (HCC). Integrated 15 transcriptomic datasets of HCC clinical samples, the first version of HCC database (HCCDB v1.0) was released in 2018. Through the meta-analysis of differentially expressed genes and prognosis-related genes across multiple datasets, it provides a systematic view of the altered biological processes and the inter-patient heterogeneities of HCC with high reproducibility and robustness. With four years having passed, the database now needs integration of recently published datasets. Furthermore, the latest single-cell and spatial transcriptomics have provided a great opportunity to decipher complex gene expression variations at the cellular level with spatial architecture. Here, we present HCCDB v2.0, an updated version that combines bulk, single-cell, and spatial transcriptomic data of HCC clinical samples. It dramatically expands the bulk sample size by adding 1656 new samples from 11 datasets to the existing 3917 samples, thereby enhancing the reliability of transcriptomic meta-analysis. A total of 182,832 cells and 69,352 spatial spots are added to the single-cell and spatial transcriptomics sections, respectively. A novel single-cell level and 2-dimension (sc-2D) metric is proposed as well to summarize cell type-specific and dysregulated gene expression patterns. Results are all graphically visualized in our online portal, allowing users to easily retrieve data through a user-friendly interface and navigate between different views. With extensive clinical phenotypes and transcriptomic data in the database, we show two applications for identifying prognosis-associated cells and tumor microenvironment. HCCDB v2.0 is available at http://lifeome.net/database/hccdb2.

Single-cell and whole-transcriptome sequencing of lymph node metastasis-related gene signature: A large-scale pan-cancer cohort, machine learning and experimental study.

BACKGROUND: Lymph node metastasis (LNM) is an independent prognostic factor in numerous types of cancer. Therefore, a LNM-related gene-based nomogram may precisely predict survival and drug sensitivity, and reveal the mechanism underlying LNM. MATERIALS AND METHODS: Gene sequencing profiles of pan-cancer data (33 cancer types) were acquired from The Cancer Genome Atlas UCSC Xena database. Patients were classified into primary (N = 10,071) and testing (N = 5,036) cohorts. The lymph node score (LNscore) was established via single-cell RNA sequencing, whole-transcriptome sequencing, machine learning, and Cox regression analyses. A novel prognosis model, formulated by incorporating the LNscore and clinical characteristics, was evaluated using the concordance index, calibration curve, and decision curve analysis. Moreover, patients were assigned into high- and low-risk groups according to the median LNscore. We investigated these two groups for survival prognosis, functional enrichment, immune infiltration, and drug sensitivity. In addition, we silenced and overexpressed insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2). We also analyzed the behavior of breast cancer (BRCA) cells regarding lymphatic metastasis and lymphangiogenesis in vitro. IGF2BP2 stimulated the proliferation of BRCA cells via 5-Ethynyl-2'-deoxyuridine and Cell Counting Kit-8 experiments. RESULTS: A LNM-related set of 12 genes was identified and utilized to determine the LNscore. The concordance-index of both cohorts in the LNscore-based model was >0.7. The immune landscape revealed that the sensitivity to immunotherapy might be better in the high-risk group versus the low-risk group. In addition, we discovered that IGF2BP2 was overexpressed in BRCA tissues and significantly associated with poor survival. Functional analysis indicated that IGF2BP2 promoted BRCA cell migration and proliferation. Additionally, IGF2BP2 accelerated lymphatic metastasis and lymphangiogenesis in vivo. CONCLUSIONS: A novel LNscore-based model was established via comprehensive analysis of LNM-related genes. This model can accurately predict patient survival and drug sensitivity, and reveal the mechanism of LNM in the pan-cancer setting.

Urinary biomarkers for hepatocellular carcinoma: current knowledge for clinicians.

Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer, causing many illnesses and deaths worldwide. The insidious clinical presentation, difficulty in early diagnosis, and the highly malignant nature make the prognosis of HCC extremely poor. The complex and heterogeneous pathogenesis of HCC poses significant challenges to developing therapies. Urine-based biomarkers for HCC, including diagnostic, prognostic, and monitoring markers, may be valuable supplements to current tools such as serum α-fetoprotein (AFP) and seem promising for progress in precision medicine. Herein, we reviewed the major urinary biomarkers for HCC and assessed their potential for clinical application. Molecular types, testing platforms, and methods for building multimolecule models in the included studies have shown great diversity, thus providing abundant novel tools for future clinical transformation and applications.

Relationship between iron overload caused by abnormal hepcidin expression and liver disease: A review.

Iron is essential to organisms, the liver plays a vital role in its storage. Under pathological conditions, iron uptake by the intestine or hepatocytes increases, allowing excess iron to accumulate in liver cells. When the expression of hepcidin is abnormal, iron homeostasis in humans cannot be regulated, and resulting in iron overload. Hepcidin also regulates the release of iron from siderophores, thereby regulating the concentration of iron in plasma. Important factors related to hepcidin and systemic iron homeostasis include plasma iron concentration, body iron storage, infection, inflammation, and erythropoietin. This review summarizes the mechanism and regulation of iron overload caused by hepcidin, as well as related liver diseases caused by iron overload and treatment.

A novel cuproptosis-related gene signature for overall survival prediction in patients with hepatocellular carcinoma.

Prognosis prediction is difficult in hepatocellular carcinoma (HCC) due to high heterogeneity and complex etiology. It has recently been discovered that cuproptosis is a type of programmed cell death. However, its significance for HCC is still unclear. We analyzed mRNA expression profiles and clinical information from public databases to determine whether cuproptosis-related genes are associated with improved prognoses for HCC patients. The training cohort consisted of HCC patients from The Cancer Genome Atlas (TCGA), and the validation cohort relied on the International Cancer Genome Consortium (ICGC) database. We constructed a signature containing four genes using the least absolute shrinkage and selection operator (LASSO) COX regression model for calculating risk scores. Two risk groups were formed based on the median score. A significant improvement in survival was observed in the low-risk group compared to the high-risk. The multivariate Cox regression analysis showed that the risk score was an independent predictor of overall survival (OS). Further confirmation of the predictive accuracy of this signature is provided by receiver operating characteristic (ROC) analysis. Functional analysis revealed differences in immune status between the two risk groups. All the results described above were confirmed in the validation cohort. Therefore, a novel cuproptosis-related signature has the potential as a prognostic biomarker for HCC patients. Drugs developed to target cuproptosis-related genes may open up new pathways for treating HCC.

eRNAs Identify Immune Microenvironment Patterns and Provide a Novel Prognostic Tool in Acute Myeloid Leukemia.

Background: Enhancer RNAs (eRNAs) play an essential role in tumorigenesis as non-coding RNAs transcribed from enhancer regions. However, the landscape of eRNAs in acute myeloid leukemia (AML) and the potential roles of eRNAs in the tumor microenvironment (TME) remain unclear. Method: Gene expression data collected from The Cancer Genome Atlas (TCGA) project were combined with Histone ChIP-seq so as to reveal the comprehensive landscape of eRNAs. Single-sample gene set enrichment analysis algorithm (ssGSEA) and ESTIMATE were employed to enumerate immune cell infiltration and tumor purity. Results: Most prognostic eRNAs were enriched in immune-related pathways. Two distinct immune microenvironment patterns, the immune-active subtype and the immune-resistant subtype, were identified in AML. We further developed an eRNA-derived score (E-score) that could quantify immune microenvironment patterns and predict the response to immune checkpoint inhibitor (ICI) treatment. Finally, we established a prognostic nomogram combining E-score and other clinical features, which showed great discriminative power in both the training set [Harrell's concordance index (C index): 0.714 (0.651-0.777), p < 0.0001] and validation set [C index: 0.684 (0.614-0.755), p < 0.0001]. Calibration of the nomogram was also validated independently. Conclusion: In this study, we systematically understood the roles of eRNAs in regulating TME diversity and complexity. Moreover, our E-score model provided the first predictive model for ICI treatment in AML.

Progress of targeted and immunotherapy for hepatocellular carcinoma and the application of next-generation sequencing.

Hepatocellular carcinoma (HCC), leading cancer worldwide, has a high degree of genetic heterogeneity; next-generation sequencing (NGS) technology has contributed significantly to the discovery of driving genes as well as high-frequency mutations in HCC. The detection of gene alterations may allow us to predict prognosis and adverse drug reactions for individuals, paving the way for personalized medicine in HCC patients. In this review, we summarized the common systemic therapy regimens for HCC and the predictive efficacy of genetic biomarkers on the prognosis of patients under these treatments. Finally, we put forward a future perspective on the potential of NGS technology for the guidance of targeted therapy and immunotherapy in HCC.

Postoperative alterations of sagittal cervical alignment and risk factors for cervical kyphosis in 124 Lenke 1 adolescent idiopathic scoliosis patients.

BACKGROUND: This study aims to analyze postoperative changes of cervical sagittal curvature and to identify independent risk factors for cervical kyphosis in Lenke type 1 adolescent idiopathic scoliosis (AIS) patients. METHODS: A total of 124 AIS patients who received all-pedicle-screw instrumentation were enrolled. All patients were followed up for at least 2 years. The following parameters were measured preoperatively, immediately after the operation, and at the last follow-up: pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), global thoracic kyphosis (GTK), proximal thoracic kyphosis (PrTK), T1-slope, cervical lordosis (CL), McGregor slope (McGS), sagittal vertical axis (SVA), C2-7 SVA (cSVA), and main thoracic angle (MTA). Statistical analysis was performed to evaluate postoperative alterations of and correlations between the parameters and to identify risk factors for cervical kyphosis. Statistical significance was set at P < 0.05. RESULTS: After the operation, PrTK and T1-slope significantly increased (3.01 ± 11.46, 3.8 ± 10.76, respectively), cervical lordosis improved with an insignificant increase (- 2.11 ± 13.47, P = 0.154), and MTA, SS, and LL decreased significantly (- 33.68 ± 15.35, - 2.98 ± 8.41, 2.82 ± 9.92, respectively). Intergroup comparison and logistic regression revealed that preoperative CK > 2.35° and immediate postoperative GTK < 27.15° were independent risk factors for final cervical kyphosis, and △T1-slope < 4.8° for a kyphotic trend. CONCLUSIONS: Postoperative restoration of thoracic kyphosis, especially proximal thoracic kyphosis, and T1-slope play a central role in cervical sagittal compensation. Preoperative CK, postoperative small GTK, and insufficient △T1-slope are all independent risk factors for cervical decompensation.