Three-dimensional chromatin landscapes in hepatocellular carcinoma associated with hepatitis B virus.

BACKGROUND: Three-dimensional (3D) chromatin architecture frequently altered in cancer. However, its changes during the pathogenesis of hepatocellular carcinoma (HCC) remained elusive. METHODS: Hi-C and RNA-seq were applied to study the 3D chromatin landscapes and gene expression of HCC and ANHT. Hi-C Pro was used to generate genome-wide raw interaction matrices, which were normalized via iterative correction (ICE). Moreover, the chromosomes were divided into different compartments according to the first principal component (E1). Furthermore, topologically associated domains (TADs) were visualized via WashU Epigenome Browser. Furthermore, differential expression analysis of ANHT and HCC was performed using the DESeq2 R package. Additionally, dysregulated genes associated with 3D genome architecture altered were confirmed using TCGA, qRT-PCR, immunohistochemistry (IHC), etc. RESULTS: First, the intrachromosomal interactions of chr1, chr2, chr5, and chr11 were significantly different, and the interchromosomal interactions of chr4-chr10, chr13-chr21, chr15-chr22, and chr16-chr19 are remarkably different between ANHT and HCC, which resulted in the up-regulation of TP53I3 and ZNF738 and the down-regulation of APOC3 and APOA5 in HCC. Second, 49 compartment regions on 18 chromosomes have significantly switched (A-B or B-A) during HCC tumorigenesis, contributing to up-regulation of RAP2A. Finally, a tumor-specific TAD boundary located on chr5: 6271000-6478000 and enhancer hijacking were identified in HCC tissues, potentially associated with the elevated expression of MED10, whose expression were associated with poor prognosis of HCC patients. CONCLUSION: This study demonstrates the crucial role of chromosomal structure variation in HCC oncogenesis and potential novel biomarkers of HCC, laying a foundation for cancer precision medicine development.

Prognostic significance of CCND1 amplification/overexpression in smoking patients with esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer, with 5-year survival rate less than 30%. In order to offer an individual therapeutic approach, it is necessary to identify novel prognostic factors to recognize high-risk patients. Given the high frequency of CCND1 abnormalities and the important biological effects of smoking in ESCC, we explored the potential relationship between CCND1 abnormalities and smoking in ESCC patients. CCND1 status was examined by fluorescence in situ hybridization and immunohistochemical staining in ESCC tissue microarrays (n = 519). CCND1 amplification and cyclinD1 overexpression were found in 53.2 and 34.1% ESCC, respectively. CCND1 amplification (P = 0.142 for DFS and P = 0.191 for OS) and cyclinD1 overexpression (P = 0.035 for DFS and P = 0.092 for OS) tended to be poorer prognostic factors in all patients. Among smoking patients, those with CCND1 amplification had significantly poorer prognosis, with a median DFS and OS of 25.0 and 30.0 months compared to not reached and 52.0 months for those without CCND1 amplification (P = 0.020 and 0.018). A similar trend was found in the 68 patients with cyclinD1 overexpression (P = 0.043 and 0.048). Further univariate and multivariate analysis revealed CCND1 amplification was independently poorer prognostic factor in smoking patients, which was not found in non-smoking patients. Smokers with CCND1 amplification or cyclinD1 overexpression have poorer survival, which help us to identify distinct groups of patients with apparently poorer outcome and would enable appropriate follow-up and treatment strategies.

Prognostic significance of CDK6 amplification in esophageal squamous cell carcinoma.

Dysregulation of CDK6 plays crucial roles in the carcinogenesis of many kinds of human malignancies. However, the role of CDK6 in esophageal squamous cell carcinoma (ESCC) is not well known. We investigated the frequency and prognostic value of CDK6 amplification to improve the risk stratification in patients with ESCC. Pan-cancer analysis of CDK6 was conducted on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. CDK6 amplification was detected in 502 ESCC samples by Fluorescence in situ hybridization (FISH) through tissue microarrays (TMA). Pan-cancer analysis revealed that CDK6 mRNA level was much higher in multiple kinds of cancers and higher CDK6 mRNA level indicated a better prognosis in ESCC. In this study, CDK6 amplification was detected in 27.5% (138/502) of patients with ESCC. CDK6 amplification was significantly correlated with tumor size (p = 0.044). Patients with CDK6 amplification tended to have a longer disease-free survival (DFS) (p = 0.228) and overall survival (OS) (p = 0.200) compared with patients without CDK6 amplification but of no significance. When further divided into I-II and III-IV stage, CDK6 amplification was significantly associated with longer DFS and OS in III-IV stage group (DFS, p = 0.036; OS, p = 0.022) rather than in I-II stage group (DFS, p = 0.776; OS, p = 0.611). On univariate and multivariate analysis of Cox hazard model, differentiation, vessel invasion, nerve invasion, invasive depth, lymph node metastasis and clinical stage were significantly associated with DFS and OS. Moreover, invasion depth was an independent factor for ESCC prognosis. Taken together, for ESCC patients in III-IV stage, CDK6 amplification indicated a better prognosis.

[Molecular markers and mechanisms for stemness maintenance of liver cancer stem cells: a review].

Primary liver cancer (PLC) is an aggressive tumor and prone to metastasize and recur. According to pathological features, PLC are mainly categorized into hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular cholangiocarcinoma, and fibrolamelic hepatocellular carcinoma, etc. At present, surgical resection, radiotherapy and chemotherapy are still the main treatments for PLC, but the specificities are poor and the clinical effects are limited with a 5-year overall survival rate of 18%. Liver cancer stem cells (LCSCs) are a specific cell subset existing in liver cancer tissues. They harbor the capabilities of self-renewal and strong tumorigenicity, driving tumor initiation, metastasis, drug resistance and recurrence of PLC. Therefore, the identification of molecular markers and the illustration of mechanisms for stemness maintenance of LCSCs can not only reveal the molecular mechanisms of PLC tumorigenesis, but also lay a theoretical foundation for the molecular classification, prognosis evaluation and targeted therapy of PLC. The latest research showed that the combination of 5-fluorouracil and CD13 inhibitors could inhibit the proliferation of CD13+ LCSCs, thereby reducing overall tumor burden. Taken together, LCSCs could be the promising therapeutic targets of PLC in the future. This review summarizes the latest progress in molecular markers, mechanisms for stemness maintenance and targeted therapies of LCSCs.

RN-Net: A Deep Learning Approach to 0-2 Hour Rainfall Nowcasting Based on Radar and Automatic Weather Station Data.

Precipitation has an important impact on people's daily life and disaster prevention and mitigation. However, it is difficult to provide more accurate results for rainfall nowcasting due to spin-up problems in numerical weather prediction models. Furthermore, existing rainfall nowcasting methods based on machine learning and deep learning cannot provide large-area rainfall nowcasting with high spatiotemporal resolution. This paper proposes a dual-input dual-encoder recurrent neural network, namely Rainfall Nowcasting Network (RN-Net), to solve this problem. It takes the past grid rainfall data interpolated by automatic weather stations and doppler radar mosaic data as input data, and then forecasts the grid rainfall data for the next 2 h. We conduct experiments on the Southeastern China dataset. With a threshold of 0.25 mm, the RN-Net's rainfall nowcasting threat scores have reached 0.523, 0.503, and 0.435 within 0.5 h, 1 h, and 2 h. Compared with the Weather Research and Forecasting model rainfall nowcasting, the threat scores have been increased by nearly four times, three times, and three times, respectively.

[Advances in three-dimensional genomics].

Three-dimensional (3D) genomics is an emerging discipline that studies the 3D spatial structure and function of genomes, focusing on the 3D spatial conformation of genome sequences in the nucleus and its biological effects on biological processes such as DNA replication, DNA recombination and gene expression regulation. The invention of chromosome conformation capture (3C) technology speeds up the research on 3D genomics and its related fields. Furthermore, the development of 3C-based technologies, such as the genome-wide chromosome conformation capture (Hi-C) and chromatin interaction analysis using paired-end tag sequencing (ChIA-PET), help scientists get insight into the 3D genomes of various species. Aims of 3D genomics are to reveal the spatial genome organization, chromosomal interaction patterns, mechanisms underlying the transcriptional regulation and formation of biological traits of microorganism, plant, animal. Additionally, the identification of key genes and signaling pathways associated with biological processes and disease via chromosome 3C technology boosts the rapid development of agricultural science, life science and medical science. This paper reviews the research progress of 3D genomics, mainly in the concept of 3D genomics, the development of chromosome 3C technologies and their applications in agricultural science, life science and medical science, specifically in the field of tumor.

[Function of tumor infiltrating lymphocytes in solid tumors - a review].

Tumor is one of the major diseases threatening human health in the 21st century. Surgical resection, radiotherapy, chemotherapy and targeted therapy are the main clinical treatments for solid tumors. However, these methods are unable to eradicate tumor cells completely, and easily lead to the recurrence and progression of tumor. Tumor immunotherapy is a novel treatment that uses human immune system to control and kill tumor by enhancing or restoring anti-tumor immunity. Tumor immunotherapy has shown to produce long-lasting responses in large numbers of patients, and thereby adoptive immunotherapy and immune checkpoint inhibitors could induce remarkable antigen-specific immune responses. Tumor infiltrating lymphocytes (TILs) are highly heterogeneous lymphocytes existing in tumor tissues and play a crucial role in host antigen-specific tumor immune response. Recent studies show that TILs are closely related to the prognosis of patients during the processes of tumorigenesis and treatment. Adoptive immunotherapy mediated by TILs has displayed favorable curative effect in many solid tumors. This paper reviews the recent progress of TILs in solid tumors.

[Progress in immunotherapy for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the malignant tumors with the highest morbidity and mortality in the world. The morbidity and mortality of HCC are increasing every year. Liver cancer is a serious threat to public health in China and the death rate of patients with liver cancer in China is the highest in the world. Beyond surgery, chemotherapy and radiotherapy, immunotherapy is an emerging treatment for cancer, which could control and kill tumor cells by relieving the inhibitory status of immune cells in the tumor microenvironment and activating the immune function of the body. Immune checkpoint inhibitors, adoptive immunotherapy and tumor vaccine are the major treatments of immunotherapy. Compared with traditional therapy methods, immunotherapy could enhance immune function, delay tumor progression, prolong the survival time of patients, and becomes a hotspot in the basic and clinical cancer research. This article reviews the research progress of immunotherapy for liver cancer.