Effect of TU-100 on Colorectal Liver Metastasis in Mouse Model of Metabolic Dysfunction-Associated Steatohepatitis.

577 Background: TU-100 is most commonly used herbal medicine in clinical setting. We have already reported that TU-100 suppressed dysbiosis (J Med Invest, 2013), bacterial translocation (Surg Today, 2017) and hepatic fibrosis (Surgery, 2016). This time we investigate the effect of TU-100 on hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in MASH model. Methods: 1: Effect on HCC: Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of MASH and HCC, were used. They were divided into a TU-100 treated group and a control group. Mice were sacrificed at 24 and 48 weeks to evaluate hepatic steatosis, fibrosis, carcinogenesis, cytokine expression, and microbiome abundance. 2: Effect on CRLM: Six-week-old male C57BL/6J mice were used. They were divided into the western diet (WD) group and the WD+TU-100 group. MC38 colon cancer cells were injected into the spleen at 16 weeks, and mice were killed at 2 weeks after injection to evaluate hepatic steatosis, fibrosis and mRNA expression in the liver. Results: 1: Effect on HCC: At 24 weeks, the TU-100 group showed significantly lower expression of IL6, IL1B, and ACTA2 mRNA in the liver (P<0.05). At 48 weeks, the TU-100 group showed a lower rate of MASH than the control group (28% vs 72%; P=0.1). Tumor diameter was significantly smaller in the TU-100 group compared with that in the control group (P<0.05). Regarding the intestinal microbiome, the genera Blautia and Ruminococcus were increased in the TU-100 group (P<0.05), whereas Dorea and Erysipelotrichaceae were decreased in the TU-100 group (P<0.05). 2: Effect on CRLM: Steatosis of the WD+TU-100 group was significantly suppressed compared with the WD group (p<0.05). The WD+TU-100 group showed significantly smaller tumor diameter than the WD group (p<0.05). In the WD+TU-100 group, expression of SAA1 and TIMP1 mRNA in the liver was significantly lower than in the WD group (p<0.05). Conclusions: TU-100 regulates the intestinal microbiome and may suppress hepatic steatosis and subsequent hepatocarcinogenesis in the MASH model. Furthermore, TU-100 may have effect on CRLM via suppression of SAA1/TIMP1.

BACKGROUNDSerum amyloid A1 (SAA1) is an acute-phase protein involved in acute or chronic hepatitis. Its function is still controversial. In addition, the effect of the expression of SAA1 and its molecular function on the progression in hepatocellular carcinoma (HCC) is still unclear.AIMTo demonstrate the expression of SAA1 and its effect on the prognosis in HCC and explain further the correlation of SAA1 and immunity pathways.METHODSSAA1 expression in HCC was conducted with The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) in GEPIA tool, and the survival analysis based on the SAA1 expression level was achieved in the Kaplan-Meier portal. The high or low expression group was then drawn based on the median level of SAA1 expression. The correlation of SAA1 and the clinical features were conducted in the UALCAN web-based portal with TCGA-LIHC, including tumor grade, patient disease stage, and the TP53 mutation. The correlation analysis between SAA1 expression and TP53 mutation was subjected to the TCGA portal. The tumor purity score and the immune score were analyzed with CIBERSORT. The correlation of SAA1 expression and tumor-infiltrating lymphocytes was achieved in TISIDB web-based integrated repository portal for tumor-immune system interactions. GSE125336 dataset was used to test the SAA1 expression in the responsive or resistant group with anti-PD1 therapy. Gene set enrichment analysis was applied to evaluate the gene enrichment signaling pathway in HCC. The similar genes of SAA1 in HCC were identified in GEPIA, and the protein-protein interaction of SAA1 was conducted in the Metascape tool. The expression of C-X-C motif chemokine ligand 2, C-C motif chemokine ligand 23, and complement C5a receptor 1 was studied and overall survival analysis in HCC was conducted in GEPIA and Kaplan-Meier portal, respectively.RESULTSSAA1 expression was decreased in HCC, and lower SAA1 expression predicted poorer overall survival, progression-free survival, and disease-specific survival. Furthermore, SAA1 expression was further decreased with increased tumor grade and patient disease stage. Also, SAA1 expression was further downregulated in patients with TP53 mutation compared with patients with wild type TP53. SAA1 expression was negatively correlated with the TP53 mutation. Lower SAA1 predicted poorer survival rate, especially in the patients with no hepatitis virus infection, other than those with hepatitis virus infection. Moreover, the SAA1 expression was negatively correlated with tumor purity. In contrast, SAA1 expression was positively correlated with the immune score in HCC, and the correlation analysis between SAA1 expression and tumor-infiltrating lymphocytes also showed a positive correlation in HCC. Decreased SAA1 was closely associated with the immune tolerance of HCC. C-X-C motif chemokine ligand 2 and C-C motif chemokine ligand 23 genes were identified as the hub genes associated with SAA1, which could also serve as favorable prognosis markers for HCC.CONCLUSIONSAA1 is downregulated in the liver tumor, and it is closely involved in the progression of HCC. Lower SAA1 expression indicates lower survival rate, especially for those patients without hepatitis virus infection. Lower SAA1 expression also suggests lower immune infiltrating cells, especially for those with immune cells exerting anti-tumor immune function. SAA1 expression is closely associated with the anti-tumor immune pathways.

We aimed to evaluate in rats whether the levels of specific miRNA are altered in the mammary gland (MG) and milk of diet-induced obese dams, and whether improving maternal nutrition during lactation attenuates such alterations. Dams fed with a standard diet (SD) (control group), with a Western diet (WD) prior to and during gestation and lactation (WD group), or with WD prior to and during gestation but moved to SD during lactation (Rev group) were followed. The WD group showed higher miR-26a, miR-222 and miR-484 levels than the controls in the MG, but the miRNA profile in Rev animals was not different from those of the controls. The WD group also displayed higher miR-125a levels than the Rev group. Dams of the WD group, but not the Rev group, displayed lower mRNA expression levels of Rb1 (miR-26a’s target) and Elovl6 (miR-125a’s target) than the controls in the MG. The WD group also presented lower expression of Insig1 (miR-26a’s target) and Cxcr4 (miR-222’s target) than the Rev group. However, both WD and Rev animals displayed lower expression of Vegfa (miR-484’s target) than the controls. WD animals also showed greater miR-26a, miR-125a and miR-222 levels in the milk than the controls, but no differences were found between the WD and Rev groups. Thus, implementation of a healthy diet during lactation normalizes the expression levels of specific miRNAs and some target genes in the MG of diet-induced obese dams but not in milk.

Consumption of a western diet (WD) is a major part of modern life contributing to the epidemic of Metabolic Syndrome (MS), a significant risk factor for cardiovascular disease. Recent studies from our laboratory have characterized a model of WD induced MS in female rats. Adopting a healthier diet may be sufficient to reverse the constellation of metabolic symptoms associated with MS including obesity-related hypertension. However, it remains unclear if returning to a normal diet overcomes cardiovascular dysfunction associated with MS. We hypothesized that cardiovascular dysfunction will persist despite diet reversal due to altered PPAR-γ, an important vascular tone regulator, in the perivascular adipose tissue (PVAT). Eight-week old female Wistar rats were fed a WD (21% fat, 50% carbohydrate (34% sucrose) for 20 weeks (WD group) to induce MS. Then, the rats were subjected to diet reversal for 8 weeks (rWD group). The control group received a regular chow diet (5% fat, 48.7% carbohydrate (3.2% sucrose). WD group exhibited increased body weight, triglyceride levels, intolerance to glucose and systolic blood pressure characterizing MS. Direct measurement of blood pressure via right carotid catheterization showed that WD increased systolic blood pressure (141.61 ± 10 vs. 119.52 ± 9 mmHg) compared with controls. Strikingly, diet reversal was unable to drop systolic blood pressure (139.87 ± 13 mmHg). WD impaired acetylcholine and sodium nitroprusside-mediated relaxation in aortic rings. These effects remained unchanged even after diet reversal. Expression of PPAR-γ in aortic PVAT was significantly reduced in the WD group (3.2 fold) and in the rWD group (2.4 fold ) compared with controls. Moreover, we found high levels of lysine acetylation in the PVAT from WD (2.8 fold ) and rWD group (2.0 fold) compared with controls. Despite reversal WD led to significant improvement of all metabolic parameters, including weight loss, this strategy was unable to reverse vascular dysfunction and elevated blood pressure caused by WD consumption. Decreased PPAR-γ expression in PVAT associated with hyperacetylation will be further examined as a potential mechanism underlying persistent vascular dysfunction in WD-induced MS.

Comparison of the Hypoglycemic Effect of Acarbose Monotherapy in Patients With Type 2 Diabetes Mellitus Consuming an Eastern or Western Diet: A Systematic Meta-analysis

Objective This study explored the colorectal cancer exosome lncRNA prostate cancer associated transcript 1– (PCAT1) mediated circulating tumors and the mechanism of cell colorectal cancer liver metastasis. Methods Exosomes were extracted from the primary colorectal cancer (CRC) cell lines HCT116 and SW480 and cultured with T84 and human umbilical vein endothelial (HUVE) cells. The expression of PCAT1 and miR-329-3p was detected by real-time quantitative polymerase chain reaction (RT-qPCR), the expression of Netrin-1, CD146, and epithelial mesenchymal transition (EMT) related proteins was detected by Western blot, the proliferation activity of T84 cells was detected by cell counting kit 8 (CCK-8), and cell migration was detected by Transwell. The expression of the F-actin signal was detected by immunofluorescence after coculture of exosomes with human umbilical vein endothelial cells (HUVECs). Changes in subcutaneous tumor and liver nodule size after PCAT1 deletion were observed in a mouse model of liver metastasis from rectal cancer. Results PCAT1 expression was upregulated in primary cell lines and their exosomes. After exosomes were cocultured with colorectal cancer tumor circulating T84 cells, the expression of Netrin-1 and CD146 was upregulated, the expression of miR-329-3p was downregulated, the proliferation and migration ability of T84 cells were enhanced, and EMT occurred. After knocking down PCAT1, the above phenomenon was reversed. Similarly, after exosomes were cocultured with HUVECs, the expression of the F-actin signal increased, and after PCAT1 was knocked down, the F-actin signal also decreased. PCAT1 regulates miR-329-3p/Netrin-1 and affects the biological behavior of T84 and F-actin signal expression in HUVECs. In a mouse model of colorectal cancer liver metastasis, knocking down PCAT1 significantly reduced the nodules formed by liver metastasis in mice. Conclusions LncRNA PCAT1 derived from colorectal cancer exosomes regulates the activity of the Netrin-1-CD146 complex in circulating tumor cells (CTCs) to promote the occurrence of colorectal cancer EMT and liver metastasis and provides new molecular targets for the treatment of colorectal cancer liver metastasis.

ObjectivesSystemic inflammation is a major risk factor for critical-illness myopathy (CIM) but its pathogenic role in muscle is uncertain. We observed that interleukin 6 (IL-6) and serum amyloid A1 (SAA1) expression was upregulated in muscle of critically ill patients. To test the relevance of these responses we assessed inflammation and acute-phase response at early and late time points in muscle of patients at risk for CIM.DesignProspective observational clinical study and prospective animal trial.SettingTwo intensive care units (ICU) and research laboratory.Patients/Subjects33 patients with Sequential Organ Failure Assessment scores ≥8 on 3 consecutive days within 5 days in ICU were investigated. A subgroup analysis of 12 patients with, and 18 patients without CIM (non-CIM) was performed. Two consecutive biopsies from vastus lateralis were obtained at median days 5 and 15, early and late time points. Controls were 5 healthy subjects undergoing elective orthopedic surgery. A septic mouse model and cultured myoblasts were used for mechanistic analyses.Measurements and Main ResultsEarly SAA1 expression was significantly higher in skeletal muscle of CIM compared to non-CIM patients. Immunohistochemistry showed SAA1 accumulations in muscle of CIM patients at the early time point, which resolved later. SAA1 expression was induced by IL-6 and tumor necrosis factor-alpha in human and mouse myocytes in vitro. Inflammation-induced muscular SAA1 accumulation was reproduced in a sepsis mouse model.ConclusionsSkeletal muscle contributes to general inflammation and acute-phase response in CIM patients. Muscular SAA1 could be important for CIM pathogenesis.Trial RegistrationISRCTN77569430.

IntroductionSepsis-associated acute kidney injury (SA-AKI) is a highly lethal condition with a rapid onset, and effective treatments are lacking because the molecular pathogenesis remains unclear. Tubular epithelial cells (TECs) have increasingly been recognized as driving forces in the progression of kidney diseases, partly through the release of extracellular vesicles (EVs) carrying proinflammatory cargos. However, the role of TEC-derived EVs on neutrophil extracellular traps (NETs) formation, which is an established feature of sepsis, and SA-AKI remains unclear.MethodsEVs isolated from phosphate buffer saline (PBS)/lipopolysaccharide (LPS)-treated TECs were injected intravenously into C57BL/6J wild type mice to determine whether TECs-derived EVs can directly induce NETs formation and kidney injury. Proteomics and single-cell RNA sequencing analysis were used to screen the key molecules that mediate the effects of TECs-derived EVs. EVs secretion from TECs and serum amyloid A1 (SAA1) expression in TECs were specifically inhibited via adeno-associated virus (AAVs). Finally, the association between SAA1 level in plasma EVs and clinical features of septic patients was determined.ResultsThis study demonstrated that EVs secreted from LPS-stimulated TECs exacerbated AKI by promoting NETs formation. Specifically blocking EVs secretion from TECs via AAVs reduced NETs formation and alleviated LPS-induced AKI. Bioinformatics analysis suggested that LPS increased SAA1 expression in TECs, and then released extracellularly through EVs. Further mechanistic studies revealed that SAA1 packaged in TECs-derived EVs was responsible for NETs formation and AKI via activation of the TLR4/p38 MAPK signaling pathway in neutrophils. Specifically inhibiting SAA1 upregulation in TECs via AAVs also reduced NETs formation and alleviated LPS-induced AKI. Interestingly, modulating EVs release from TECs or SAA1 expression in TECs also alleviated remote lung injury induced by LPS, indicated that TECs-derived EVs may participate in kidney‒lung crosstalk during sepsis. Furthermore, plasma TECs-derived EVs proportion and SAA1 expression in plasma EVs may be promising prognostic indexes for SA-AKI patients.DiscussionHere, we explored a new mode of TECs-neutrophils crosstalk mediated by EVs during SA-AKI, and strategies to modify TECs-derived EVs and the cargo SAA1 could be a new avenue for developing therapeutics against SA-AKI.

The tumor microenvironment (TME) plays an important part in the initiation and development of clear cell renal cell carcinoma (ccRCC). However, an understanding of the immune infiltration in TME is still unknown. Our study aims to explore the correlation between the TME and the clinical features, as well as the prognosis of ccRCC. In the present study, ESTIMATE and CIBERSORT computational methods were applied to calculate the proportion of tumor-infiltrating immune cells (TICs) and the amount of immune and stromal fractions in the ccRCC form The Cancer Genome Atlas (TCGA) database. Then, we sought to find out those immune cell types and genes which may play a significant role and validated them in the GEO database. Furthermore, an immunohistochemical analysis of our external validation dataset was used to detect SAA1 and PDL1 expression in the ccRCC cancer tissues and corresponding normal tissues. Statistical analysis was performed to study the relationship between SAA1 and clinical characteristics, as well as PDL1 expression. Furthermore, a ccRCC cell model with SAA1 knockdown was constructed, which was used for cell proliferation and the migration test. The intersection analysis of the univariate COX and PPI analysis were performed to imply Serum Amyloid A1 (SAA1) as a predictive factor. The expression of SAA1 was significantly negatively correlated to OS and positively correlated to the clinical TMN stage system. The genes in the high-expression SAA1 group were basically enriched in immune-related activities. The proportion of mast cells resting was negatively correlated with SAA1 expression, indicating that SAA1 may be involved in the maintenance of the immune status for the TME. Moreover, the PDL1 expression was positively related to the SAA1 expression and negatively correlated with the patients’ prognosis. Further experiments revealed that the knockdown of SAA1 inhibited ccRCC development through suppressing cell proliferation and migration. SAA1 may be a novel marker for the prognosis prediction of ccRCC patients and may play a vital role in the TME by mast cell resting and PDL1 expression. SAA1 has the potential to become a therapeutic target and indicator for immune target therapy in ccRCC treatment.

In this study, it was aimed to investigate the effects of different diets on lipid peroxidation, antioxidants, proliferation and vasculogenesis in liver tissue. BALBC female rats (21) were divided as the group fed with standard chow (SC), the group fed with a ketogenic diet (KD) and the group fed with western diet (WD). The rats were fed with tap water and a rat diet specially prepared according to the determined diets for 4 weeks. Liver tissue oxidative damage, proliferation and vasculogenesis were evaluated using spectrophotometric and immunohistopathological methods. At the end of the experiment, it was found that the highest weight gain was in the WD group and the least weight gain was in the KD group. The mean body weight of the WD group was statistically significantly higher compared to the SC and KD groups (p<0.05). MDA levels were found to be lower in the KD group compared to the SC and WD groups. GSH and CAT levels were higher in the KD group compared to the SC and WD groups. In IHC evaluation results, it was seen that Ki-67 percentage in the KD group increased compared to the WD and SC groups (p = 0.000), VEGF was close to each other in all three groups and there was no significant difference in the comparisons between groups (p>0.05). These results revealed that ketogenic diet prevents tissue damage by decreasing lipid peroxidation in liver tissue as well as inducing cellular proliferation and vasculogenesis.

In this study, it was aimed to investigate the effects of different diets on lipid peroxidation, antioxidants, proliferation and vasculogenesis in liver tissue. BALBC female rats (21) were divided as the group fed with standard chow (SC), the group fed with a ketogenic diet (KD) and the group fed with western diet (WD). The rats were fed with tap water and a rat diet specially prepared according to the determined diets for four weeks. Liver tissue oxidative damage, proliferation and vasculogenesis were evaluated using spectrophotometric and immunohistopathological methods. At the end of the experiment, it was found that the highest weight gain was in the WD group and the least weight gain was in the KD group. The mean body weight of the WD group was statistically significantly higher compared to the SC and KD groups (p<0.05). MDA levels were found to be lower in the KD group compared to the SC and WD groups. GSH and CAT levels were higher in the KD group compared to the SC and WD groups. In IHC evaluation results, it was seen that Ki-67 percentage in the KD group increased compared to the WD and SC groups (p = 0.000), VEGF was close to each other in all three groups and there was no significant difference in the comparisons between groups (p>0.05). These results revealed that ketogenic diet prevents tissue damage by decreasing lipid peroxidation in liver tissue as well as inducing cellular proliferation and vasculogenesis.

BackgroundOverconsumption of a WD, a high‐fat and high‐sugar diet, has plagued the United States contributing to the widespread prevalence of type 2 diabetes (T2DM). Insulin resistance (IR) plays a key role in the development of T2DM and is a consistent finding among T2DM patients. The pathogenesis of IR, however, is not well understood. Based on recent evidence that inflammation precedes IR, and previous findings from our lab showing involvement of Toll‐like receptor 4 (TLR4) signaling in diabetic vascular inflammation, we hypothesize that WD leads to pancreatic inflammation through TLR4 signaling activation, contributing to IR.MethodsOur lab has established a model of a WD‐induced metabolic syndrome and IR in female rats. Eight‐week old female Wistar rats were randomized into two experimental groups: Control (n = 9) and WD group (n = 16). The control group received a regular chow diet (5% fat, 48.7% carbohydrates [3.2% sucrose], and 24.1% protein), while the WD group received a WD (40% fat, 43% carbohydrates [34% sucrose], 17% protein), for 28 weeks. Body weight and food consumption were measured weekly. Lipid and glucose metabolism, and intraperitoneal glucose tolerance tests (IPGTT) were measured. Quantitative IR was assessed using Homeostasis Model Assessment of Insulin Resistance (HOMA‐IR), while functional beta cell capacity was assessed via HOMA‐B calculation. At the terminal experiments, pancreas’ were isolated for molecular (TLR4 signaling) and histological (hematoxylin and eosin, H&E) analysis.ResultsWD group exhibited greater body weight (415.1 ± 30.9 vs. 323.0 ± 24.0 g controls, p<0.01), and increased daily caloric consumption (130.5 ± 7.36 vs.110.7 ± 7.0 kcals controls, p<0.05) in spite of a significant reduction in daily food intake (23.7 ± 1.5 vs. 31.5 ± 1.8 g controls, p<0.01). WD negatively interfered in the glucose metabolism as evidenced by increased blood glucose area under the curve during IPGTT (17531.8 ± 574.3 vs. 12381.25 ± 1480.6 a.u. controls, p<0.001). IR in the WD group was confirmed by increased HOMA‐IR (8.09 ± 1.90 vs. 2.05 ± .042 a.u. controls, p<0.001), which was accompanied by hyperinsulinemia (0.93 ± 0.1 vs. 0.30 ± 0.09 mg/dL controls, p<0.01). No changes were observed in the HOMA‐B, suggesting that β cells remain functional. Moreover, no evidence of vacuolation, irregular outlining and size of the Langerhans islets, which are all markers of β cell dysfunction, were observed in the H&E stained pancreatic section from the WD group. Pancreatic inflammation in the WD group was confirmed by a 42% increase in TNF‐α expression (p<0.05), an inflammatory marker. Strikingly, pancreatic TLR4 (1.8‐fold increased, p<0.05) and its downstream molecule TNF‐receptor associated factor 6 (TRAF6) (3.1‐fold increased, p<0.001) were markedly upregulated in the WD group in comparison to controls, indicating TLR4/TRAF6 signaling activation in the pancreas.ConclusionOur findings suggest that a WD can induce IR along with activation of pancreatic TLR4 signaling‐related inflammation. These results can provide new insights into how high fat and fat sugar diet choices can causes inflammation in the pancreas.Support or Funding InformationNIH

Sialylated IgG-activated integrin β4-Src-Erk axis stabilizes c-Myc in a p300 lysine acetyltransferase-dependent manner to promote colorectal cancer liver metastasis.

Aristolochic acid (AA) ingestion causes Balkan nephropathy, characterized by tubular injury and progression to chronic kidney disease (CKD). AA is taken up by proximal tubule cells via organic anion transport (OAT3) and induces p53-mediated DNA damage, but little is known about modulating factors. The Western diet (WD) is rich in saturated fats, sugars, and salt and contributes to the development of metabolic disorders such as obesity and diabetes, but also to the progression of CKD. The aim of this study was to elucidate the impact of WD on AA-induced kidney injury. 5-week-old male C57BL6 mice were fed with WD or normal chow (NC) for 8 weeks, followed by administration of AA every 3 days at a dose of 3 mg/kg for 3 weeks. Samples were collected after a 3-week recovery period (n=4/group for vehicle; n=7-8/group for AA). The AA-induced increase in plasma creatinine and the reduction of hematocrit were significantly greater in WD vs NC. This was associated with increased kidney gene expression in WD vs NC of markers of DNA damage ( p53), injury ( Kim1 and Ngal), and inflammation ( Tnfa). The WD group had a greater body weight and, therefore, received a higher total dose of AA (0.73 and 0.6 mg), which may have worsened kidney injury. Therefore, in a second series, the same total dose of AA (0.9 mg) was administered to WD and NC groups. WD similarly increased the AA-induced fall in hematocrit and rise in plasma creatinine and renal p53, Kim1, Ngal, and Tnfa mRNA expression compared to the NC group. Moreover, WD increased renal mRNA expression of Oat3. These findings suggest that WD increases the susceptibility to AA nephrotoxicity, possibly through upregulation of OAT3. This model may be useful for studying the mechanistic impact of Western diet on the development and progression of CKD caused by nephrotoxic agents. Supported by National Institutes of Health (NIH) Grants RF1AG061296 (PM, VV), R01DK132690 (VV), and P30 DK079337 (VV), the Department of Veterans Affairs, and a fellowship of the Manpei Suzuki Diabetes Foundation (YO). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Glioblastoma (GBM) is the most lethal tumour in the central nervous system (CNS), GBM has a poor prognosis due to treatment tolerance and tumour recurrence; new molecular biomarkers are needed to acquire accurate prognosis and to promote therapeutic strategies. Data from Gene Expression Omnibus (GEO) was analysed to screen differentially expressed genes (DEGs), and 279 DEGs were screened. The protein–protein interaction (PPI) network of DEGs was constructed and visualized, top 10 hub genes were identified by using Cytoscape consequently. The function of DEGs was explored by enrichment analysis, DEGs were enriched in tumour-associated biologic processions and pathways. Gene Expression Profiling Interactive Analysis (GEPIA) database was used to identify prognostic genes; serum amyloid A1 (SAA1) was identified as a critical prognostic gene due to higher SAA1 expression associated with poor overall survival (OS) (HR = 1.5, p < .05) and poor disease-free survival (DFS) (HR = 1.9, p < .01). Dataset from The Chinese Glioma Genome Atlas database validated the prognostic value of SAA1 and reported the relationship between SAA1 expression and clinical characteristics, including age, sex, history of relapse, and the status of IDH. Gene set enrichment analysis (GSEA) identified six SAA1-related pathways; the identification of pathways could provide insight into the therapeutic strategies of GBM. Lastly, the relationship between SAA1 expression and immune infiltration was explored, and the result showed that SAA1 expression negatively correlated with the infiltration level of T cells, and SAA1 expression positively correlated with the infiltration level of Treg cells. The overexpression of SAA1 was associated with poor OS and DFS in GBM, and the expression of the SAA1 gene may affect the infiltration level of immune cells. Therefore, SAA1 could be a promising prognostic biomarker associated with immune infiltration and therapeutic target for GBM.