Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma

BackgroundPrevious studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC).MethodsBased on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of LPCAT1 knockdown on HCC cell behavior was verified using in vitro experiments.ResultsThis study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene LPCAT1 was upregulated in HCC cell lines. LPCAT1 knockdown markedly decreased HCC cell proliferation and migration.ConclusionPANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment

Crosslinked microporous polyarylate membranes with high Kr/Xe separation performance and high stability under irradiation

The Kr/Xe separation based on membranes is of great significance for radioactive Kr capture from nuclear fuel reprocessing plants and expensive Xe production, thus the membrane material that has both high separation performance and stability is highly sought after. Herein, the crosslinked polymeric micro-porous polyarylate (PAR) membrane was synthesized by interfacial polymerization, and its Kr/Xe separation performance and stability under various conditions including γ irradiation were investigated. The PAR membrane displays Kr permeance of 0.22 GPU and Kr/Xe selectivity of 3.6 tested with mixed gas at room temperature, which is better than other reported polymeric membranes and even better than the amorphous carbon membrane. After the γ irradiation, the PAR can preserve its chemical structures, while the physical ageing is accelerated, which leads to only 25% decrease in Kr/Xe selectivity after 20 kGy irradiation. This work demonstrates that the micro-porosity and the crosslinking structures play crucial roles in improving both separation performance and stability of polymeric membranes for radioactive Kr/Xe separation

DataSheet_1_Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma.docx

BackgroundPrevious studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC).MethodsBased on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of LPCAT1 knockdown on HCC cell behavior was verified using in vitro experiments.ResultsThis study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene LPCAT1 was upregulated in HCC cell lines. LPCAT1 knockdown markedly decreased HCC cell proliferation and migration.ConclusionPANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment.</p