Predictive value of a stemness-based classifier for prognosis and immunotherapy response of hepatocellular carcinoma based on bioinformatics and machine-learning strategies

ObjectiveSignificant advancements have been made in hepatocellular carcinoma (HCC) therapeutics, such as immunotherapy for treating patients with HCC. However, there is a lack of reliable biomarkers for predicting the response of patients to therapy, which continues to be challenging. Cancer stem cells (CSCs) are involved in the oncogenesis, drug resistance, and invasion, as well as metastasis of HCC cells. Therefore, in this study, we aimed to create an mRNA expression-based stemness index (mRNAsi) model to predict the response of patients with HCC to immunotherapy.MethodsWe retrieved gene expression and clinical data of patients with HCC from the GSE14520 dataset and the Cancer Genome Atlas (TCGA) database. Next, we used the “one-class logistic regression (OCLR)” algorithm to obtain the mRNAsi of patients with HCC. We performed “unsupervised consensus clustering” to classify patients with HCC based on the mRNAsi scores and stemness subtypes. The relationships between the mRNAsi model, clinicopathological features, and genetic profiles of patients were compared using various bioinformatic methods. We screened for differentially expressed genes to establish a stemness-based classifier for predicting the patient’s prognosis. Next, we determined the effect of risk scores on the tumor immune microenvironment (TIME) and the response of patients to immune checkpoint blockade (ICB). Finally, we used qRT-PCR to investigate gene expression in patients with HCC.ResultsWe screened CSC-related genes using various bioinformatics tools in patients from the TCGA-LIHC cohort. We constructed a stemness classifier based on a nine-gene (PPARGC1A, FTCD, CFHR3, MAGEA6, CXCL8, CABYR, EPO, HMMR, and UCK2) signature for predicting the patient’s prognosis and response to ICBs. Further, the model was validated in an independent GSE14520 dataset and performed well. Our model could predict the status of TIME, immunogenomic expressions, congenic pathway, and response to chemotherapy drugs. Furthermore, a significant increase in the proportion of infiltrating macrophages, Treg cells, and immune checkpoints was observed in patients in the high-risk group. In addition, tumor cells in patients with high mRNAsi scores could escape immune surveillance. Finally, we observed that the constructed model had a good expression in the clinical samples. The HCC tumor size and UCK2 genes expression were significantly alleviated and decreased, respectively, by treatments of anti-PD1 antibody. We also found knockdown UCK2 changed expressions of immune genes in HCC cell lines.ConclusionThe novel stemness-related model could predict the prognosis of patients and aid in creating personalized immuno- and targeted therapy for patients in HCC

Improvement of the Accuracy of InSAR Image Co-Registration Based On Tie Points – A Review

Interferometric Synthetic Aperture Radar (InSAR) is a new measurement technology, making use of the phase information contained in the Synthetic Aperture Radar (SAR) images. InSAR has been recognized as a potential tool for the generation of digital elevation models (DEMs) and the measurement of ground surface deformations. However, many critical factors affect the quality of InSAR data and limit its applications. One of the factors is InSAR data processing, which consists of image co-registration, interferogram generation, phase unwrapping and geocoding. The co-registration of InSAR images is the first step and dramatically influences the accuracy of InSAR products. In this paper, the principle and processing procedures of InSAR techniques are reviewed. One of important factors, tie points, to be considered in the improvement of the accuracy of InSAR image co-registration are emphatically reviewed, such as interval of tie points, extraction of feature points, window size for tie point matching and the measurement for the quality of an interferogram

Theoretical And Numerical Analysis On A Thermo-Elastic System With Discontinuities

. A second order accurate numerical scheme is proposed for a thermo-elastic system which models a bar made of two distinct materials. The physical parameters involved may be discontinuous across the joint of the two materials, where there might be also singular heat and/or force sources. The solution components, the temperature and the displacement, may change rapidly across the joint. By transforming the system into a different one, time-marching schemes can be used for the new system which is well-posed. The immersed interface method is employed to deal with the discontinuities of the coefficients and the singular sources. The proposed numerical method can fit both explicit and implicit formulation. For the implicit version, a stable and fast Prediction-Correction scheme is also developed. Convergence analysis shows that our method is second order accurate at all grid points in spite of the discontinuities across the interface. Numerical experiments are performed to support the theor..

Theoretical and numerical analysis on a thermo-elastic system with discontinuities

A second-order accurate numerical scheme is proposed for a thermo-elastic system which models a bar made of two distinct materials. The physical parameters involved may be discontinuous across the joint of the two materials, where there might be also singular heat and/or force sources. The solution components, the temperature and the displacement, may change rapidly across the joint. By transforming the system into a different one, time-marching schemes can be used for the new system which is well posed. The immersed interface method is employed to deal with the discontinuities of the coefficients and the singular sources. The proposed numerical method can fit both explicit and implicit formulation. For the implicit version, a stable and fast prediction-correction scheme is also developed. Convergence analysis shows that our method is second-order accurate at all grid points in spite of the discontinuities across the interface. Numerical experiments are performed to support the theoretical analysis in this paper

A stand-alone Co mineral deposit in northeastern Hunan Province, South China: Its timing, origin of ore fluids and metal Co, and geodynamic setting

The Hengdong cobalt (Co) deposit, located in northeastern Hunan Province of South China, is hosted by the low-grade metamorphic volcaniclastic sedimentary rocks of the early Neoproterozoic Lengjiaxi Group. The Co orebodies strictly controlled by the NE- to ENE-trending Changsha-Pingjiang deep fault zone (CPDFZ) and its secondary structures. Occurring in altered breccias and cataclasites with similar mineral assemblages, Co mineralization is characterized by zoned alteration with predominant silicification and chloritization proximal to the orebodies, and sericitization and carbonatization distal from the mineralization. The integrated field and microscope observations reveal three hydrothermal stages marked by quartz + pyrite + muscovite chalcopyrite of the early-stage mineralization (E-stage), quartz + polymetallic sulfides + chlorite of the middle stage mineralization (M - stage), and quartz + chlorite + carbonate of the late-stage mineralization (L-stage). Muscovite from both the E-stage Co-bearing altered breccia and the CPDFZ mylonite yield Ar-40-Ar-39 plateau ages of 124.7 +/- 0.6 Ma (1 sigma) and 130.3 +/- 1.4 Ma (1 sigma), respectively, indicating an early Cretaceous mineralization likely associated with the last movement of CPDFZ strike-slip shearing. The 8345 values of pyrite and chalcopyrite ranging from -1.5 to -15.9% with a majority between -7.5 and -15.9%, and the lead isotope compositions of the pyrite (Pb-206/Pb-204 = 18.156-18.761, Pb-207/Pb-204 = 15.645-15.662 and Pb-208/Pb-204 = 38.469-39.172) overlapping with those of upper crust, indicate a main crust-derived source. The chemical compositions of pyrite further indicate the ore fluids and metal Co of the Hengdong deposit are most likely linked to the meta-mafic and volcanic rocks of the Neoarchean to Paleoproterozoic Lianyunshan Group, but with a contamination by the wall rocks of Lengjiaxi Group and Lianyunshan granitoids. Fluid inclusion investigations from Hengdong deposit reveal the decreasing homogenization temperatures from similar to 250 to 320 degrees C (peak of 280-300 degrees C) at the E stage, through similar to 220-320 degrees C (peak of 270-300 degrees C) at the M stage, and to similar to 150-230 degrees C at the L stage without obviously salinity (7.0-15 wt% NaCI equiv.) changed. In the M - stage, the presence of coexisting LV inclusions and V-rich inclusions with the similar homogenization temperature, consistent with the chlorite geothermometry data, is interpreted to be the result of fluid immiscibility, which was caused by cyclic pressure release during fault-zone movement. Combined with the Late Mesozoic tectonism of South China, the present data support the Hengdong deposit formed under an extension-associated tectonic regime most likely induced by slab roll-back of the subducted Paleo-Pacific Plate during the early Cretaceous. This extensional event not only caused the reactivation of the pre-existing structures as manifested by the CPDFZ characteristic of stress transformation from compression to extension but also likely resulted in the release of large amounts of Co-bearing ore fluids from the Proterozoic or older volcanogenic rocks. When the ore fluids migrated along the CPDFZ and its secondary faults, the decompression (adiabatic cooling) of the hydrothermal fluids shifted the ore fluid to the immiscibility field, significantly reduced the degree of cobalt undersaturation, and caused cobalt to precipitate, which finally formed the Hengdong Co mineral deposit