Image_2_Identification of subclusters and prognostic genes based on glycolysis/gluconeogenesis in hepatocellular carcinoma.tif

BackgroundThis study aimed to examine glycolysis/gluconeogenesis-related genes in hepatocellular carcinoma (HCC) and evaluate their potential roles in HCC progression and immunotherapy response.MethodsData analyzed in this study were collected from GSE14520, GSE76427, GSE174570, The Cancer Genome Atlas (TCGA), PXD006512, and GSE149614 datasets, metabolic pathways were collected from MSigDB database. Differentially expressed genes (DEGs) were identified between HCC and controls. Differentially expressed glycolysis/gluconeogenesis-related genes (candidate genes) were obtained and consensus clustering was performed based on the expression of candidate genes. Bioinformatics analysis was used to evaluate candidate genes and screen prognostic genes. Finally, the key results were tested in HCC patients.ResultsThirteen differentially expressed glycolysis/gluconeogenesis-related genes were validated in additional datasets. Consensus clustering analysis identified two distinct patient clusters (C1 and C2) with different prognoses and immune microenvironments. Immune score and tumor purity were significantly higher in C1 than in C2, and CD4+ memory activated T cell, Tfh, Tregs, and macrophage M0 were higher infiltrated in HCC and C1 group. The study also identified five intersecting DEGs from candidate genes in TCGA, GSE14520, and GSE141198 as prognostic genes, which had a protective role in HCC patient prognosis. Compared with the control group, the prognostic genes all showed decreased expression in HCC patients in RT-qPCR and Western blot analyses. Flow cytometry verified the abnormal infiltration level of immune cells in HCC patients.ConclusionResults showed that glycolysis/gluconeogenesis-related genes were associated with patient prognosis, immune microenvironment, and response to immunotherapy in HCC. It suggests that the model based on five prognostic genes may valuable for predicting the prognosis and immunotherapy response of HCC patients.</p

Plasma Level of Placenta-Derived Macrophage-Stimulating Protein -Chain in Preeclampsia before 20 Weeks of Pregnancy

<div><p>Object</p><p>This study aimed to investigate the diagnostic value of placenta-derived macrophage-stimulating protein α-chain (MSP-α) before the 20^th week of gestation for the early diagnosis of preeclampsia (PE).</p><p>Methods and Materials</p><p>Two parts of this nested case-control study were simultaneously executed, and 1500 pregnant women were recruited. A total of 124 pregnant women were included in the plasma analysis part of this study. The MSP-α plasma level was measured before the 20^th week of gestation, and the participants were followed until delivery. A case group of 62 women with PE and a control group of 62 women matched by gestational age, maternal age, and pre-pregnancy BMI (with normotensive pregnancies) were evaluated. In the placenta analysis part of this nested case-control study, the placentas of 34 pregnant women were randomly obtained. The placental levels of MSP were measured in 17 individuals with PE (case group) and in 17 women with a normotensive pregnancy matched by gestational age and maternal age (control group).</p><p>Results</p><p>The plasma level of MSP-α was higher in the PE group than in the control group before the 20^th week of gestation (p < 0.001). In addition, compared to the women with severe features in the PE group, those without severe features had a significantly higher plasma MSP-α level before the 20^th week of gestation (p < 0.001). The area under the receiver operating characteristic curve (AUC) of MSP-α before the 20^th week of gestation was 0.905 (95% CI, 0.811–0.962) for the women with early-onset PE without severe features. With regard to the placenta, the PE group (accumulated optical density, IOD [SUM] = 8862.37 ± 2064.42) exhibited increased MSP staining (more intense MSP staining or more extensive staining) compared with the control group (normal pregnancies (IOD [SUM] = 447.92 ± 114.72, P < 0.001). Furthermore, increased MSP staining was detected among the women without severe features compared with those with severe features in the PE group (IOD [SUM]: 12192.65 ± 5325.56 vs. 4104.83 ± 2383.06, P = 0.021).</p><p>Conclusion</p><p>According to the findings of this study, the plasma level of MSP-α may be associated with PE, and MSP-α may be considered a candidate protein for further analysis in studies of PE. Multicenter studies with larger sample sizes must be performed in the future to obtain accurate results regarding the predictive value of MSP-α in combination with other protein factors for the early diagnosis of PE.</p></div

Demographic and Clinical Characteristics of the PE and Control Groups.

<p>Demographic and Clinical Characteristics of the PE and Control Groups.</p

Immunohistochemical analysis of the placentas revealed that the patients with PE exhibited significantly increased plasma MSP staining (IOD [SUM] = 8862.37±2064.42) compared with the healthy pregnant controls (IOD [SUM] = 447.92±114.72, P <0.001).

<p>A significant difference in MSP staining was observed between the PE group without severe features (IOD [SUM]: 12192.65±5325.56) and the PE group with severe features (4104.83±2383.06; P = 0.021).</p

Image_5_Identification of subclusters and prognostic genes based on glycolysis/gluconeogenesis in hepatocellular carcinoma.tif

BackgroundThis study aimed to examine glycolysis/gluconeogenesis-related genes in hepatocellular carcinoma (HCC) and evaluate their potential roles in HCC progression and immunotherapy response.MethodsData analyzed in this study were collected from GSE14520, GSE76427, GSE174570, The Cancer Genome Atlas (TCGA), PXD006512, and GSE149614 datasets, metabolic pathways were collected from MSigDB database. Differentially expressed genes (DEGs) were identified between HCC and controls. Differentially expressed glycolysis/gluconeogenesis-related genes (candidate genes) were obtained and consensus clustering was performed based on the expression of candidate genes. Bioinformatics analysis was used to evaluate candidate genes and screen prognostic genes. Finally, the key results were tested in HCC patients.ResultsThirteen differentially expressed glycolysis/gluconeogenesis-related genes were validated in additional datasets. Consensus clustering analysis identified two distinct patient clusters (C1 and C2) with different prognoses and immune microenvironments. Immune score and tumor purity were significantly higher in C1 than in C2, and CD4+ memory activated T cell, Tfh, Tregs, and macrophage M0 were higher infiltrated in HCC and C1 group. The study also identified five intersecting DEGs from candidate genes in TCGA, GSE14520, and GSE141198 as prognostic genes, which had a protective role in HCC patient prognosis. Compared with the control group, the prognostic genes all showed decreased expression in HCC patients in RT-qPCR and Western blot analyses. Flow cytometry verified the abnormal infiltration level of immune cells in HCC patients.ConclusionResults showed that glycolysis/gluconeogenesis-related genes were associated with patient prognosis, immune microenvironment, and response to immunotherapy in HCC. It suggests that the model based on five prognostic genes may valuable for predicting the prognosis and immunotherapy response of HCC patients.</p

Image_1_Identification of subclusters and prognostic genes based on glycolysis/gluconeogenesis in hepatocellular carcinoma.tif

BackgroundThis study aimed to examine glycolysis/gluconeogenesis-related genes in hepatocellular carcinoma (HCC) and evaluate their potential roles in HCC progression and immunotherapy response.MethodsData analyzed in this study were collected from GSE14520, GSE76427, GSE174570, The Cancer Genome Atlas (TCGA), PXD006512, and GSE149614 datasets, metabolic pathways were collected from MSigDB database. Differentially expressed genes (DEGs) were identified between HCC and controls. Differentially expressed glycolysis/gluconeogenesis-related genes (candidate genes) were obtained and consensus clustering was performed based on the expression of candidate genes. Bioinformatics analysis was used to evaluate candidate genes and screen prognostic genes. Finally, the key results were tested in HCC patients.ResultsThirteen differentially expressed glycolysis/gluconeogenesis-related genes were validated in additional datasets. Consensus clustering analysis identified two distinct patient clusters (C1 and C2) with different prognoses and immune microenvironments. Immune score and tumor purity were significantly higher in C1 than in C2, and CD4+ memory activated T cell, Tfh, Tregs, and macrophage M0 were higher infiltrated in HCC and C1 group. The study also identified five intersecting DEGs from candidate genes in TCGA, GSE14520, and GSE141198 as prognostic genes, which had a protective role in HCC patient prognosis. Compared with the control group, the prognostic genes all showed decreased expression in HCC patients in RT-qPCR and Western blot analyses. Flow cytometry verified the abnormal infiltration level of immune cells in HCC patients.ConclusionResults showed that glycolysis/gluconeogenesis-related genes were associated with patient prognosis, immune microenvironment, and response to immunotherapy in HCC. It suggests that the model based on five prognostic genes may valuable for predicting the prognosis and immunotherapy response of HCC patients.</p

Image_4_Identification of subclusters and prognostic genes based on glycolysis/gluconeogenesis in hepatocellular carcinoma.tif

BackgroundThis study aimed to examine glycolysis/gluconeogenesis-related genes in hepatocellular carcinoma (HCC) and evaluate their potential roles in HCC progression and immunotherapy response.MethodsData analyzed in this study were collected from GSE14520, GSE76427, GSE174570, The Cancer Genome Atlas (TCGA), PXD006512, and GSE149614 datasets, metabolic pathways were collected from MSigDB database. Differentially expressed genes (DEGs) were identified between HCC and controls. Differentially expressed glycolysis/gluconeogenesis-related genes (candidate genes) were obtained and consensus clustering was performed based on the expression of candidate genes. Bioinformatics analysis was used to evaluate candidate genes and screen prognostic genes. Finally, the key results were tested in HCC patients.ResultsThirteen differentially expressed glycolysis/gluconeogenesis-related genes were validated in additional datasets. Consensus clustering analysis identified two distinct patient clusters (C1 and C2) with different prognoses and immune microenvironments. Immune score and tumor purity were significantly higher in C1 than in C2, and CD4+ memory activated T cell, Tfh, Tregs, and macrophage M0 were higher infiltrated in HCC and C1 group. The study also identified five intersecting DEGs from candidate genes in TCGA, GSE14520, and GSE141198 as prognostic genes, which had a protective role in HCC patient prognosis. Compared with the control group, the prognostic genes all showed decreased expression in HCC patients in RT-qPCR and Western blot analyses. Flow cytometry verified the abnormal infiltration level of immune cells in HCC patients.ConclusionResults showed that glycolysis/gluconeogenesis-related genes were associated with patient prognosis, immune microenvironment, and response to immunotherapy in HCC. It suggests that the model based on five prognostic genes may valuable for predicting the prognosis and immunotherapy response of HCC patients.</p

The plasma level of MSP-α in the patients with severe features was significantly lower than that in the patients without severe features before the 20^th week of gestation (141.61 ± 51.01 ng/mL vs. 204.86 ± 51.79 ng/mL, p < 0.001).

<p>The levels in the case groups were significantly higher compared with that in the control group (204.86 ± 51.79 ng/mL vs. 141.61 ± 51.01 ng/mL vs. 107.97± 40.60 ng/mL, p < 0.001).</p

Immunohistochemical analysis of the placentas revealed that the patients with PE exhibited significantly increased plasma RON staining (IOD [SUM] = 2540.15±637.76) compared with the healthy pregnant controls (IOD [SUM] = 1375.87±365.03, P <0.001).

<p>A significant difference in RON staining was detected between the PE group without severe features (IOD (SUM):3611.78±1020.86) and the PE group with severe features (1009.25±158.36; P = 0.017).</p

Table_1_Identification of subclusters and prognostic genes based on glycolysis/gluconeogenesis in hepatocellular carcinoma.docx

BackgroundThis study aimed to examine glycolysis/gluconeogenesis-related genes in hepatocellular carcinoma (HCC) and evaluate their potential roles in HCC progression and immunotherapy response.MethodsData analyzed in this study were collected from GSE14520, GSE76427, GSE174570, The Cancer Genome Atlas (TCGA), PXD006512, and GSE149614 datasets, metabolic pathways were collected from MSigDB database. Differentially expressed genes (DEGs) were identified between HCC and controls. Differentially expressed glycolysis/gluconeogenesis-related genes (candidate genes) were obtained and consensus clustering was performed based on the expression of candidate genes. Bioinformatics analysis was used to evaluate candidate genes and screen prognostic genes. Finally, the key results were tested in HCC patients.ResultsThirteen differentially expressed glycolysis/gluconeogenesis-related genes were validated in additional datasets. Consensus clustering analysis identified two distinct patient clusters (C1 and C2) with different prognoses and immune microenvironments. Immune score and tumor purity were significantly higher in C1 than in C2, and CD4+ memory activated T cell, Tfh, Tregs, and macrophage M0 were higher infiltrated in HCC and C1 group. The study also identified five intersecting DEGs from candidate genes in TCGA, GSE14520, and GSE141198 as prognostic genes, which had a protective role in HCC patient prognosis. Compared with the control group, the prognostic genes all showed decreased expression in HCC patients in RT-qPCR and Western blot analyses. Flow cytometry verified the abnormal infiltration level of immune cells in HCC patients.ConclusionResults showed that glycolysis/gluconeogenesis-related genes were associated with patient prognosis, immune microenvironment, and response to immunotherapy in HCC. It suggests that the model based on five prognostic genes may valuable for predicting the prognosis and immunotherapy response of HCC patients.</p